Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.

Ms. H, age 42, is being treated by her family physician for her second episode of major depressive disorder (MDD). When she was 35, Ms. H experienced her first episode of MDD, which was successfully treated with fluoxetine, 20 mg/d, for 9 months. The current episode began approximately 3 months ago, and there were no known precipitating factors. Because Ms. H had responded well to fluoxetine, her physician reinitiates fluoxetine, 20 mg/d, for 8 weeks.

At the 8-week follow-up appointment, the physician notes how much better Ms. H seems to be doing. He says that because she has had such a good response, she should continue the fluoxetine and come back in 3 months. Later that evening, Ms. H reflects on her visit. Although she feels better, she still does not feel normal. In fact, she is not sure that she has really felt normal since before her first depressive episode. Ms. H decides to see a psychiatrist.

At her first appointment, the psychiatrist asks Ms. H to complete the Quick Inventory of Depressive Symptoms–Self Rated (QIDS-SR) scale. Her QIDS-SR score is 6, which is consistent with mild residual symptoms of depression.¹ The psychiatrist increases the fluoxetine dosage to 40 mg/d and recommends that she complete a course of cognitive-behavioral therapy (CBT).

Although psychiatry currently does not have tests that provide continuous data such as blood pressure or HbA_1c, well-validated rating scales can help clinicians in getting their patients to achieve symptom remission. Measurement-based care is the “systematic use of measurement tools to monitor progress and guide treatment choices.”¹ Originally, psychometric rating scales were designed for research; typically, they were administered by the clinician, and were too long to be used in routine outpatient clinical practice. Subsequently, it was determined that patients without psychotic symptoms or cognitive deficits can accurately assess their own symptoms, and this led to the development of short self-assessment scales that have a high level of reliability when compared with longer, clinician-administered instruments. Despite the availability of several validated, brief rating scales, it is estimated that only approximately 18% of psychiatrists use them in clinical practice.²

Self-rated scales for depression have been shown to be as valid as clinician-rated scales. For depression, the Patient Health Questionaire-9 (PHQ-9), based on the 9 symptom criteria associated with a diagnosis of MDD, is likely the most commonly used self-assessment scale.¹ However, the QIDS-SR and the Beck Depression Inventory are both well-validated.¹ In particular, QIDS-SR scores and score changes have been shown to be comparable with those on the QIDS-Clinician Rating (QIDS-C) scale.³ A 50% decrease in score typically is defined as a clinical response. Remission of symptoms is often defined as a score ≤4 on the PHQ-9 or ≤5 on the QIDS-SR (Table¹). Similar to laboratory tests, rating scales are not diagnostic, but are a piece of information for the clinician to use in making diagnostic and treatment decisions.

Continue to: Optimizing the use of self-rating scales...

Optimizing the use of self-rating scales

To save time, patients can complete a rating scale before seeing the clinician, and the use of computerized applications can automatically sum scores and plot response graphs.⁴ Some researchers have suggested that some patients may be more honest in completing a self-assessment than in their verbal responses to the clinician.⁴ It is important to discuss the rating scale results with the patient.² With a newly diagnosed patient, goals for treatment and the treatment plan can be outlined. During follow-up visits, clinicians should note areas of improvement and provide encouragement. If the patient’s symptoms are not improving appropriately, the clinician should discuss treatment options and offer the patient hope. This may improve the patient’s engagement in care and their understanding of how symptoms are associated with their illness.² Studies have suggested that the use of validated rating tools (along with other interventions) can result in faster improvement in symptoms and higher response rates, and can assist in achieving remission.^1,2,5

CASE CONTINUED

After 6 weeks of CBT and the increased fluoxetine dose, Ms. H returns to her psychiatrist for a follow-up visit. Her QIDS-SR score is 4, which is down from her initial score of 6. Ms. H is elated when she sees that her symptoms score has decreased since the previous visit. To confirm this finding, the psychiatrist completes the QIDS-C, and records a score of 3. The psychiatrist discusses the appropriate continuation of fluoxetine and CBT.

In this case, the use of a brief clinical rating scale helped Ms. H’s psychiatrist identify residual depressive symptoms and modify treatment so that she achieved remission. Using patient-reported outcomes also helps facilitate meaningful conversations between the patient and clinician and helps identify symptoms suggestive of relapse.² Although this case focused on the use of measurement-based care in depression, brief symptom rating scales for most major psychiatric disorders—many of them self-assessments—also are available, as are brief rating scales to assess medication adverse effects and adherence.⁵

Just as clinicians in other areas of medicine use assessments such as laboratory tests and blood pressure monitoring for initial assessment and in following response to treatment, measurement-based care allows for a quasi-objective evaluation of patients with psychiatric disorders. Improved response rates, time to response, and patient engagement are all positive results of measurement-based care

Related Resources

• Martin-Cook K, Palmer L, Thornton L, et al. Setting measurement-based care in motion: practical lessons in the implementation and integration of measurement-based care in psychiatry clinical practice. Neuropsychiatric Disease & Treatment. 2021;17:1621-1631.
• Aboraya A, Nasrallah HA, Elswick DE, et al. Measurementbased care in psychiatry-past, present, and future. Innov Clin Neurosci. 2018;15(11-12):13-26.

Drug Brand Names

Fluoxetine • Prozac

Ms. H, age 42, is being treated by her family physician for her second episode of major depressive disorder (MDD). When she was 35, Ms. H experienced her first episode of MDD, which was successfully treated with fluoxetine, 20 mg/d, for 9 months. The current episode began approximately 3 months ago, and there were no known precipitating factors. Because Ms. H had responded well to fluoxetine, her physician reinitiates fluoxetine, 20 mg/d, for 8 weeks.

At the 8-week follow-up appointment, the physician notes how much better Ms. H seems to be doing. He says that because she has had such a good response, she should continue the fluoxetine and come back in 3 months. Later that evening, Ms. H reflects on her visit. Although she feels better, she still does not feel normal. In fact, she is not sure that she has really felt normal since before her first depressive episode. Ms. H decides to see a psychiatrist.

At her first appointment, the psychiatrist asks Ms. H to complete the Quick Inventory of Depressive Symptoms–Self Rated (QIDS-SR) scale. Her QIDS-SR score is 6, which is consistent with mild residual symptoms of depression.¹ The psychiatrist increases the fluoxetine dosage to 40 mg/d and recommends that she complete a course of cognitive-behavioral therapy (CBT).

Although psychiatry currently does not have tests that provide continuous data such as blood pressure or HbA_1c, well-validated rating scales can help clinicians in getting their patients to achieve symptom remission. Measurement-based care is the “systematic use of measurement tools to monitor progress and guide treatment choices.”¹ Originally, psychometric rating scales were designed for research; typically, they were administered by the clinician, and were too long to be used in routine outpatient clinical practice. Subsequently, it was determined that patients without psychotic symptoms or cognitive deficits can accurately assess their own symptoms, and this led to the development of short self-assessment scales that have a high level of reliability when compared with longer, clinician-administered instruments. Despite the availability of several validated, brief rating scales, it is estimated that only approximately 18% of psychiatrists use them in clinical practice.²

Self-rated scales for depression have been shown to be as valid as clinician-rated scales. For depression, the Patient Health Questionaire-9 (PHQ-9), based on the 9 symptom criteria associated with a diagnosis of MDD, is likely the most commonly used self-assessment scale.¹ However, the QIDS-SR and the Beck Depression Inventory are both well-validated.¹ In particular, QIDS-SR scores and score changes have been shown to be comparable with those on the QIDS-Clinician Rating (QIDS-C) scale.³ A 50% decrease in score typically is defined as a clinical response. Remission of symptoms is often defined as a score ≤4 on the PHQ-9 or ≤5 on the QIDS-SR (Table¹). Similar to laboratory tests, rating scales are not diagnostic, but are a piece of information for the clinician to use in making diagnostic and treatment decisions.

Continue to: Optimizing the use of self-rating scales...

Optimizing the use of self-rating scales

To save time, patients can complete a rating scale before seeing the clinician, and the use of computerized applications can automatically sum scores and plot response graphs.⁴ Some researchers have suggested that some patients may be more honest in completing a self-assessment than in their verbal responses to the clinician.⁴ It is important to discuss the rating scale results with the patient.² With a newly diagnosed patient, goals for treatment and the treatment plan can be outlined. During follow-up visits, clinicians should note areas of improvement and provide encouragement. If the patient’s symptoms are not improving appropriately, the clinician should discuss treatment options and offer the patient hope. This may improve the patient’s engagement in care and their understanding of how symptoms are associated with their illness.² Studies have suggested that the use of validated rating tools (along with other interventions) can result in faster improvement in symptoms and higher response rates, and can assist in achieving remission.^1,2,5

CASE CONTINUED

After 6 weeks of CBT and the increased fluoxetine dose, Ms. H returns to her psychiatrist for a follow-up visit. Her QIDS-SR score is 4, which is down from her initial score of 6. Ms. H is elated when she sees that her symptoms score has decreased since the previous visit. To confirm this finding, the psychiatrist completes the QIDS-C, and records a score of 3. The psychiatrist discusses the appropriate continuation of fluoxetine and CBT.

In this case, the use of a brief clinical rating scale helped Ms. H’s psychiatrist identify residual depressive symptoms and modify treatment so that she achieved remission. Using patient-reported outcomes also helps facilitate meaningful conversations between the patient and clinician and helps identify symptoms suggestive of relapse.² Although this case focused on the use of measurement-based care in depression, brief symptom rating scales for most major psychiatric disorders—many of them self-assessments—also are available, as are brief rating scales to assess medication adverse effects and adherence.⁵

Just as clinicians in other areas of medicine use assessments such as laboratory tests and blood pressure monitoring for initial assessment and in following response to treatment, measurement-based care allows for a quasi-objective evaluation of patients with psychiatric disorders. Improved response rates, time to response, and patient engagement are all positive results of measurement-based care

Related Resources

• Martin-Cook K, Palmer L, Thornton L, et al. Setting measurement-based care in motion: practical lessons in the implementation and integration of measurement-based care in psychiatry clinical practice. Neuropsychiatric Disease & Treatment. 2021;17:1621-1631.
• Aboraya A, Nasrallah HA, Elswick DE, et al. Measurementbased care in psychiatry-past, present, and future. Innov Clin Neurosci. 2018;15(11-12):13-26.

Drug Brand Names

Fluoxetine • Prozac

Ms. H, age 42, is being treated by her family physician for her second episode of major depressive disorder (MDD). When she was 35, Ms. H experienced her first episode of MDD, which was successfully treated with fluoxetine, 20 mg/d, for 9 months. The current episode began approximately 3 months ago, and there were no known precipitating factors. Because Ms. H had responded well to fluoxetine, her physician reinitiates fluoxetine, 20 mg/d, for 8 weeks.

At the 8-week follow-up appointment, the physician notes how much better Ms. H seems to be doing. He says that because she has had such a good response, she should continue the fluoxetine and come back in 3 months. Later that evening, Ms. H reflects on her visit. Although she feels better, she still does not feel normal. In fact, she is not sure that she has really felt normal since before her first depressive episode. Ms. H decides to see a psychiatrist.

At her first appointment, the psychiatrist asks Ms. H to complete the Quick Inventory of Depressive Symptoms–Self Rated (QIDS-SR) scale. Her QIDS-SR score is 6, which is consistent with mild residual symptoms of depression.¹ The psychiatrist increases the fluoxetine dosage to 40 mg/d and recommends that she complete a course of cognitive-behavioral therapy (CBT).

Although psychiatry currently does not have tests that provide continuous data such as blood pressure or HbA_1c, well-validated rating scales can help clinicians in getting their patients to achieve symptom remission. Measurement-based care is the “systematic use of measurement tools to monitor progress and guide treatment choices.”¹ Originally, psychometric rating scales were designed for research; typically, they were administered by the clinician, and were too long to be used in routine outpatient clinical practice. Subsequently, it was determined that patients without psychotic symptoms or cognitive deficits can accurately assess their own symptoms, and this led to the development of short self-assessment scales that have a high level of reliability when compared with longer, clinician-administered instruments. Despite the availability of several validated, brief rating scales, it is estimated that only approximately 18% of psychiatrists use them in clinical practice.²

Self-rated scales for depression have been shown to be as valid as clinician-rated scales. For depression, the Patient Health Questionaire-9 (PHQ-9), based on the 9 symptom criteria associated with a diagnosis of MDD, is likely the most commonly used self-assessment scale.¹ However, the QIDS-SR and the Beck Depression Inventory are both well-validated.¹ In particular, QIDS-SR scores and score changes have been shown to be comparable with those on the QIDS-Clinician Rating (QIDS-C) scale.³ A 50% decrease in score typically is defined as a clinical response. Remission of symptoms is often defined as a score ≤4 on the PHQ-9 or ≤5 on the QIDS-SR (Table¹). Similar to laboratory tests, rating scales are not diagnostic, but are a piece of information for the clinician to use in making diagnostic and treatment decisions.

Continue to: Optimizing the use of self-rating scales...

Optimizing the use of self-rating scales

To save time, patients can complete a rating scale before seeing the clinician, and the use of computerized applications can automatically sum scores and plot response graphs.⁴ Some researchers have suggested that some patients may be more honest in completing a self-assessment than in their verbal responses to the clinician.⁴ It is important to discuss the rating scale results with the patient.² With a newly diagnosed patient, goals for treatment and the treatment plan can be outlined. During follow-up visits, clinicians should note areas of improvement and provide encouragement. If the patient’s symptoms are not improving appropriately, the clinician should discuss treatment options and offer the patient hope. This may improve the patient’s engagement in care and their understanding of how symptoms are associated with their illness.² Studies have suggested that the use of validated rating tools (along with other interventions) can result in faster improvement in symptoms and higher response rates, and can assist in achieving remission.^1,2,5

CASE CONTINUED

After 6 weeks of CBT and the increased fluoxetine dose, Ms. H returns to her psychiatrist for a follow-up visit. Her QIDS-SR score is 4, which is down from her initial score of 6. Ms. H is elated when she sees that her symptoms score has decreased since the previous visit. To confirm this finding, the psychiatrist completes the QIDS-C, and records a score of 3. The psychiatrist discusses the appropriate continuation of fluoxetine and CBT.

In this case, the use of a brief clinical rating scale helped Ms. H’s psychiatrist identify residual depressive symptoms and modify treatment so that she achieved remission. Using patient-reported outcomes also helps facilitate meaningful conversations between the patient and clinician and helps identify symptoms suggestive of relapse.² Although this case focused on the use of measurement-based care in depression, brief symptom rating scales for most major psychiatric disorders—many of them self-assessments—also are available, as are brief rating scales to assess medication adverse effects and adherence.⁵

Just as clinicians in other areas of medicine use assessments such as laboratory tests and blood pressure monitoring for initial assessment and in following response to treatment, measurement-based care allows for a quasi-objective evaluation of patients with psychiatric disorders. Improved response rates, time to response, and patient engagement are all positive results of measurement-based care

Related Resources

• Martin-Cook K, Palmer L, Thornton L, et al. Setting measurement-based care in motion: practical lessons in the implementation and integration of measurement-based care in psychiatry clinical practice. Neuropsychiatric Disease & Treatment. 2021;17:1621-1631.
• Aboraya A, Nasrallah HA, Elswick DE, et al. Measurementbased care in psychiatry-past, present, and future. Innov Clin Neurosci. 2018;15(11-12):13-26.

Drug Brand Names

Fluoxetine • Prozac

Consider the following patients who have presented to our hospital system:

• A 27-year-old gay man is brought to the emergency department by police after bizarre behavior in a hotel. He is paranoid, disorganized, and responding to internal stimuli. He admits to using methamphetamine before a potential “hookup” at the hotel
• A 35-year-old bisexual man presents to the psychiatric emergency department, worried he will lose his job and relationship after downloading a dating app on his work phone to buy methamphetamine
• A 30-year-old gay man divulges to his psychiatrist that he is insecure about his sexual performance and intimacy with his partner because most of their sexual contact involves using gamma-hydroxybutyric acid (GHB).

These are just some of the many psychiatric presentations we have encountered involving “chemsex” among men who have sex with men (MSM).

What is ‘chemsex?’

“Chemsex” refers to the use of specific drugs—mainly methamphetamine, mephedrone, or GHB—before or during sex to reduce sexual disinhibitions and to facilitate, initiate, prolong, sustain, and intensify the encounter.¹ Chemsex participants report desired enhancements in:

• confidence and ability to engage with partners
• emotional awareness and shared experience with partners
• sexual performance and intensity of sensations.¹

How prevalent is it?

Emerging in urban centers as a part of gay nightlife, chemsex has become increasingly prevalent among young MSM, fueled by a worldwide rise in methamphetamine use.^1,2 In a large 2019 systematic review, Maxwell et al¹ reported a wide range of chemsex prevalence estimates among MSM (3% to 29%). Higher estimates emerged from studies recruiting participants from sexual health clinics and through phone-based dating apps, while lower estimates tended to come from more representative samples of MSM. In studies from the United States, the prevalence of chemsex ranged from 9% to 10% in samples recruited from gay pride events, gay nightlife venues, and internet surveys. Across studies, MSM participating in chemsex were more likely to identify as gay, with mean ages ranging from 32 to 42 years, and were more likely to be HIV-positive.¹

Methamphetamine was the most popular drug used, with GHB having higher prevalence in Western Europe, and mephedrone more common in the United Kingdom.¹ Injection drug use was only examined in studies from the United Kingdom, the Netherlands, and Australia and showed a lower overall prevalence rate—1% to 9%. Methamphetamine was the most commonly injected drug. Other drugs used for chemsex included ketamine, 3,4-methylenedioxymethamphetamine (MDMA, aka “ecstasy”), cocaine, amyl nitrite (“poppers”), and erectile dysfunction medications.¹It is important to remember that chemsex is a socially constructed concept and, as such, is subject to participant preferences and the popularity and availability of specific drugs. These features are likely to vary across geography, subcultures, and time. The above statistics ultimately represent a minority of MSM but highlight the importance of considering this phenomenon when caring for this population.¹

Continue to: What makes chemsex unique?...

What makes chemsex unique?

Apps and access. Individuals who engage in chemsex report easy access to drugs via nightlife settings or through smartphone dating apps. Drugs are often shared during sexual encounters, which removes cost barriers for participants.¹

Environment. Chemsex sometimes takes place in group settings at “sex-on-premises venues,” including clubs, bathhouses, and saunas. The rise of smartphone apps and closure of these venues has shifted much of chemsex to private settings.¹Sexual behavior. Seventeen of the studies included in the Maxwell et al¹ review showed an increased risk of condomless anal intercourse during chemsex. Several studies also reported increased rates of sex with multiple partners and new partners.¹

What are the potential risks?

Physical health. High-risk sexual behaviors associated with chemsex increase the risk of sexually transmitted infections, including HIV and hepatitis C.¹ Use of substances associated with chemsex can lead to overdose, cardiovascular events, and neurotoxicity.^1,2

Mental health. In our clinical experience, the psychiatric implications of chemsex are numerous and exist on a spectrum from acute to chronic (Table 1).

What can clinicians do?

We encourage you to talk about chemsex with your patients. Table 2 provides a “tip sheet” to help you start the conversation, address risks, and provide support. We hope you continue to learn from your patients and keep up-to-date on this evolving topic.

Consider the following patients who have presented to our hospital system:

• A 27-year-old gay man is brought to the emergency department by police after bizarre behavior in a hotel. He is paranoid, disorganized, and responding to internal stimuli. He admits to using methamphetamine before a potential “hookup” at the hotel
• A 35-year-old bisexual man presents to the psychiatric emergency department, worried he will lose his job and relationship after downloading a dating app on his work phone to buy methamphetamine
• A 30-year-old gay man divulges to his psychiatrist that he is insecure about his sexual performance and intimacy with his partner because most of their sexual contact involves using gamma-hydroxybutyric acid (GHB).

These are just some of the many psychiatric presentations we have encountered involving “chemsex” among men who have sex with men (MSM).

What is ‘chemsex?’

“Chemsex” refers to the use of specific drugs—mainly methamphetamine, mephedrone, or GHB—before or during sex to reduce sexual disinhibitions and to facilitate, initiate, prolong, sustain, and intensify the encounter.¹ Chemsex participants report desired enhancements in:

• confidence and ability to engage with partners
• emotional awareness and shared experience with partners
• sexual performance and intensity of sensations.¹

How prevalent is it?

Emerging in urban centers as a part of gay nightlife, chemsex has become increasingly prevalent among young MSM, fueled by a worldwide rise in methamphetamine use.^1,2 In a large 2019 systematic review, Maxwell et al¹ reported a wide range of chemsex prevalence estimates among MSM (3% to 29%). Higher estimates emerged from studies recruiting participants from sexual health clinics and through phone-based dating apps, while lower estimates tended to come from more representative samples of MSM. In studies from the United States, the prevalence of chemsex ranged from 9% to 10% in samples recruited from gay pride events, gay nightlife venues, and internet surveys. Across studies, MSM participating in chemsex were more likely to identify as gay, with mean ages ranging from 32 to 42 years, and were more likely to be HIV-positive.¹

Methamphetamine was the most popular drug used, with GHB having higher prevalence in Western Europe, and mephedrone more common in the United Kingdom.¹ Injection drug use was only examined in studies from the United Kingdom, the Netherlands, and Australia and showed a lower overall prevalence rate—1% to 9%. Methamphetamine was the most commonly injected drug. Other drugs used for chemsex included ketamine, 3,4-methylenedioxymethamphetamine (MDMA, aka “ecstasy”), cocaine, amyl nitrite (“poppers”), and erectile dysfunction medications.¹It is important to remember that chemsex is a socially constructed concept and, as such, is subject to participant preferences and the popularity and availability of specific drugs. These features are likely to vary across geography, subcultures, and time. The above statistics ultimately represent a minority of MSM but highlight the importance of considering this phenomenon when caring for this population.¹

Continue to: What makes chemsex unique?...

What makes chemsex unique?

Apps and access. Individuals who engage in chemsex report easy access to drugs via nightlife settings or through smartphone dating apps. Drugs are often shared during sexual encounters, which removes cost barriers for participants.¹

Environment. Chemsex sometimes takes place in group settings at “sex-on-premises venues,” including clubs, bathhouses, and saunas. The rise of smartphone apps and closure of these venues has shifted much of chemsex to private settings.¹Sexual behavior. Seventeen of the studies included in the Maxwell et al¹ review showed an increased risk of condomless anal intercourse during chemsex. Several studies also reported increased rates of sex with multiple partners and new partners.¹

What are the potential risks?

Physical health. High-risk sexual behaviors associated with chemsex increase the risk of sexually transmitted infections, including HIV and hepatitis C.¹ Use of substances associated with chemsex can lead to overdose, cardiovascular events, and neurotoxicity.^1,2

Mental health. In our clinical experience, the psychiatric implications of chemsex are numerous and exist on a spectrum from acute to chronic (Table 1).

What can clinicians do?

We encourage you to talk about chemsex with your patients. Table 2 provides a “tip sheet” to help you start the conversation, address risks, and provide support. We hope you continue to learn from your patients and keep up-to-date on this evolving topic.

Consider the following patients who have presented to our hospital system:

• A 27-year-old gay man is brought to the emergency department by police after bizarre behavior in a hotel. He is paranoid, disorganized, and responding to internal stimuli. He admits to using methamphetamine before a potential “hookup” at the hotel
• A 35-year-old bisexual man presents to the psychiatric emergency department, worried he will lose his job and relationship after downloading a dating app on his work phone to buy methamphetamine
• A 30-year-old gay man divulges to his psychiatrist that he is insecure about his sexual performance and intimacy with his partner because most of their sexual contact involves using gamma-hydroxybutyric acid (GHB).

These are just some of the many psychiatric presentations we have encountered involving “chemsex” among men who have sex with men (MSM).

What is ‘chemsex?’

“Chemsex” refers to the use of specific drugs—mainly methamphetamine, mephedrone, or GHB—before or during sex to reduce sexual disinhibitions and to facilitate, initiate, prolong, sustain, and intensify the encounter.¹ Chemsex participants report desired enhancements in:

• confidence and ability to engage with partners
• emotional awareness and shared experience with partners
• sexual performance and intensity of sensations.¹

How prevalent is it?

Emerging in urban centers as a part of gay nightlife, chemsex has become increasingly prevalent among young MSM, fueled by a worldwide rise in methamphetamine use.^1,2 In a large 2019 systematic review, Maxwell et al¹ reported a wide range of chemsex prevalence estimates among MSM (3% to 29%). Higher estimates emerged from studies recruiting participants from sexual health clinics and through phone-based dating apps, while lower estimates tended to come from more representative samples of MSM. In studies from the United States, the prevalence of chemsex ranged from 9% to 10% in samples recruited from gay pride events, gay nightlife venues, and internet surveys. Across studies, MSM participating in chemsex were more likely to identify as gay, with mean ages ranging from 32 to 42 years, and were more likely to be HIV-positive.¹

Methamphetamine was the most popular drug used, with GHB having higher prevalence in Western Europe, and mephedrone more common in the United Kingdom.¹ Injection drug use was only examined in studies from the United Kingdom, the Netherlands, and Australia and showed a lower overall prevalence rate—1% to 9%. Methamphetamine was the most commonly injected drug. Other drugs used for chemsex included ketamine, 3,4-methylenedioxymethamphetamine (MDMA, aka “ecstasy”), cocaine, amyl nitrite (“poppers”), and erectile dysfunction medications.¹It is important to remember that chemsex is a socially constructed concept and, as such, is subject to participant preferences and the popularity and availability of specific drugs. These features are likely to vary across geography, subcultures, and time. The above statistics ultimately represent a minority of MSM but highlight the importance of considering this phenomenon when caring for this population.¹

Continue to: What makes chemsex unique?...

What makes chemsex unique?

Apps and access. Individuals who engage in chemsex report easy access to drugs via nightlife settings or through smartphone dating apps. Drugs are often shared during sexual encounters, which removes cost barriers for participants.¹

Environment. Chemsex sometimes takes place in group settings at “sex-on-premises venues,” including clubs, bathhouses, and saunas. The rise of smartphone apps and closure of these venues has shifted much of chemsex to private settings.¹Sexual behavior. Seventeen of the studies included in the Maxwell et al¹ review showed an increased risk of condomless anal intercourse during chemsex. Several studies also reported increased rates of sex with multiple partners and new partners.¹

What are the potential risks?

Physical health. High-risk sexual behaviors associated with chemsex increase the risk of sexually transmitted infections, including HIV and hepatitis C.¹ Use of substances associated with chemsex can lead to overdose, cardiovascular events, and neurotoxicity.^1,2

Mental health. In our clinical experience, the psychiatric implications of chemsex are numerous and exist on a spectrum from acute to chronic (Table 1).

What can clinicians do?

We encourage you to talk about chemsex with your patients. Table 2 provides a “tip sheet” to help you start the conversation, address risks, and provide support. We hope you continue to learn from your patients and keep up-to-date on this evolving topic.

The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,¹ Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.² David’s transgressions are enabled by the very success he has achieved.³

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”¹  

Continue to: Mark S. Komrad, MD...

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.¹ Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al² discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.³ Alang⁴ discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.² It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al² found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,¹ Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.² David’s transgressions are enabled by the very success he has achieved.³

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”¹  

Continue to: Mark S. Komrad, MD...

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.¹ Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al² discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.³ Alang⁴ discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.² It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al² found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,¹ Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.² David’s transgressions are enabled by the very success he has achieved.³

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”¹  

Continue to: Mark S. Komrad, MD...

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.¹ Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al² discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.³ Alang⁴ discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.² It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al² found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

dbrunk@mdedge.com

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme