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Nevada Psychiatric Association (NPA): Annual Psychopharmacology Update
Ideal agent for insomnia not always clear cut
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2;2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA-nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said.
"One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine-receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the nonbenzodiazepines (also known as selective benzodiazepine-receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin-receptor agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
Dr. Paul A. Selecky, FCCP, comments: This is a well written and concise review of the common medications and other agents used in the treatment of insomnia to guide clinicians, pointing out the caution that the non-prescription items have limited scientific evidence to support their regular use. Some of the prescription medications are reviewed as well.
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2;2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA-nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said.
"One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine-receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the nonbenzodiazepines (also known as selective benzodiazepine-receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin-receptor agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
Dr. Paul A. Selecky, FCCP, comments: This is a well written and concise review of the common medications and other agents used in the treatment of insomnia to guide clinicians, pointing out the caution that the non-prescription items have limited scientific evidence to support their regular use. Some of the prescription medications are reviewed as well.
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2;2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA-nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said.
"One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine-receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the nonbenzodiazepines (also known as selective benzodiazepine-receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin-receptor agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
Dr. Paul A. Selecky, FCCP, comments: This is a well written and concise review of the common medications and other agents used in the treatment of insomnia to guide clinicians, pointing out the caution that the non-prescription items have limited scientific evidence to support their regular use. Some of the prescription medications are reviewed as well.
Ideal agent for insomnia not always clear cut
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
LAS VEGAS – Many patients with insomnia reach for certain dietary supplements and herbal preparations for relief, but their efficacies have not been established in well-controlled studies.
"Dietary supplements and herbal preparations not regulated by the FDA [Food and Drug Administration]," Dr. Karl Doghramji said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "There is some question about the purity of these agents, and also about the active ingredient. There are many ingredients in these so-called nutraceutical compounds. Which is the active ingredient? We’re not quite sure."
If clinicians recommend agents whose effectiveness is not well-established, "are we delaying treatment for insomnia and other conditions, which may have a negative impact in daytime performance and may impair mood?" asked Dr. Doghramji, professor of psychiatry, neurology, and medicine at Thomas Jefferson University, Philadelphia. "That’s a concern."
One of the more commonly used natural supplements for insomnia is valerian in a dose of 400-450 mg/day. This herb is believed to have some anxiolytic, muscle relaxant, and sleep-promoting properties, "yet data regarding efficacy are mixed," said Dr. Doghramji, who also directs the university’s Sleep Disorders Center. "Safety data are scant, yet side effects appear to be rare and mild, primarily GI irritation and headache. There are case reports of hepatotoxicity in persons taking herbal products containing valerian."
He described melatonin as the most commonly used natural supplement for insomnia. A review of 139 published studies commissioned by the Agency for Healthcare Research and Quality suggests that melatonin has no effectiveness in the treatment of everyday regular insomnia (AHRQ Publication No. 05-E002-2; 2004). "But, some evidence suggests that it is effective in treating delayed sleep-phase syndrome with short-term use," Dr. Doghramji noted. "On the other hand, evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use, and no evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder."
Certain prescription agents might benefit patients with insomnia, he continued. FDA nonapproved agents for insomnia include sedating antidepressants, antipsychotics, and anticonvulsants. FDA-approved hypnotics include benzodiazepine-receptor agonists, melatonin-receptor agonists, and H1-receptor antagonists.
"At appropriate doses, sedating antidepressants are effective for mood and anxiety disorders; there is a low abuse risk, low cost, and there is a large dose range," Dr. Doghramji said. "One of the disadvantages is that they tend to be long acting and have anticholinergic and antihistaminic side effects." A 42-day controlled study of doxepin 25-50 mg found that the agent did not produce any change in terms of sleep latency (J. Clin. Psychiatry 2001;62:453-63). However, "it did increase their total sleep time, suggesting that they didn’t necessarily fall asleep more quickly, but they had fewer awakenings after they did fall asleep," he said. "So, if doxepin is to be used for insomnia, it seems to be best suited for the insomnia characterized by middle of the night awakening and late morning insomnia."
A 2-week study that compared trazodone with zolpidem in primary insomnia demonstrated that trazodone did seem to help people fall asleep more quickly in the first week or so (Hum. Psychopharmacol. 1998;13:191-8). "It also helped them feel as though they had slept longer," said Dr. Doghramji, who was not involved with the study. "The problem was, tolerance occurred within 2 weeks. The issue there is, should you increase the dosage or keep the same dosage for a while? We don’t have a lot of data on this."
From a pharmacokinetic standpoint, trazodone has a long half-life (5-12 hours) and features a complex set of pharmacodynamics. "It not only has some serotonergic potential, it has some histaminic potential, making it an agent that can have multiple side effects, so be careful with it," he said.
Clinicians likely use benzodiazepine receptor agonists more than any other agent for insomnia. These include the benzodiazepines, such as estazolam, flurazepam, quazepam, temazepam, and triazolam; and the non-benzodiazepines (also known as selective benzodiazepine receptor agonists) such as zaleplon, zolpidem and its various preparations (oral, sublingual, and oral spray); and eszopiclone. Adverse effects may include daytime sedation, psychomotor and cognitive impairment (depending on dose and half-life), rebound insomnia, and respiratory depression in vulnerable populations. All of these are classified as schedule IV controlled substance by the Drug Enforcement Administration. New drugs, which do not have a DEA schedule classification, include ramelteon, a melatonin receptor-agonist, and low-dose doxepin.
Choosing which antidepressant agent to use for a patient with depression and comorbid insomnia poses a certain clinical dilemma, Dr. Doghramji concluded. "Do you start with a sedating agent when your patient is both depressed and cannot sleep? Or do you put them on any old agent, regardless of whether it’s sedating or not? Unfortunately, at this point, there are not a lot of data guiding us on this."
Dr. Doghramji disclosed that he is a consultant for UCB, Teva Pharmaceuticals, Vanda Pharmaceuticals, and Jazz Pharmaceuticals, and that he holds stock in Merck.
EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE
Treating anorexia nervosa requires multifocused approach
LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.
"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "
Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."
The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."
The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m2 or greater) to moderate (16-16.99 kg/m2), severe (BM, 15-15.99 kg/m2), or extreme (BMI less than 15 kg/m2). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."
The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.
Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."
Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.
Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."
According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.
Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."
Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."
Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."
Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.
Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.
Dr. Halmi said she had no relevant financial conflicts to disclose.
LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.
"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "
Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."
The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."
The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m2 or greater) to moderate (16-16.99 kg/m2), severe (BM, 15-15.99 kg/m2), or extreme (BMI less than 15 kg/m2). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."
The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.
Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."
Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.
Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."
According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.
Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."
Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."
Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."
Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.
Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.
Dr. Halmi said she had no relevant financial conflicts to disclose.
LAS VEGAS – Patients with anorexia nervosa rank among the most difficult to manage because of their resistance to treatment, according to Dr. Katherine A. Halmi.
"Patients with this disorder characteristically do not wish to be treated; they are terrified to give up their illness," Dr. Halmi, professor emerita of psychiatry at Weill Cornell Medical College, New York, said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "They know the diagnostic criteria better than most clinicians do. If you ask them, are you afraid of gaining weight? Many of them will say, ‘No, I don’t know what’s happening. I’m not afraid of gaining weight.’ "
Marked by a restriction of calorie intake leading to low body weight, patients with anorexia nervosa also have a disturbance in experience of body weight or shape or undue influence of body weight or shape on self-evaluation. "Patients will focus on certain body parts, like how wide their thighs are, or they will walk in a peculiar way so their thighs won’t touch," explained Dr. Halmi, who founded the eating disorders program at the New York–Presbyterian Hospital/Westchester division. "When they look in the mirror they will focus on their abdomen and become very concerned that they’re too wide. But if you take a photograph of them and show them the photograph, they will acknowledge that they are thin."
The two subgroups of patients with anorexia nervosa include those who lose weight only by restricting what they eat (no binge eating or purging in the past 3 months) and those who lose weight by binge eating/purging (binge eating, self-induced vomiting, or misuse of laxatives or enemas in the past 3 months). The new aspect of diagnosing this in the DSM-5 includes qualifiers for partial remission or full remission. "Partial remission is defined as weight recovery but continued fear/preoccupation with body weight and shape," she said. "Full remission is defined as no criteria for anorexia nervosa met for a sustained period of time."
The severity of anorexia nervosa is measured by body mass index, ranging from mild (body mass index, 17 kg/m2 or greater) to moderate (16-16.99 kg/m2), severe (BM, 15-15.99 kg/m2), or extreme (BMI less than 15 kg/m2). The level of severity may be increased for clinical symptoms, functional disability, and the need for supervision. "This is a serious, chronic illness," Dr. Halmi said. "You have to treat these patients sometimes for 2-3 years before they recover."
The psychological characteristics of the illness include a perfectionist need to control, inflexible thinking, obsessive-compulsive features and social withdrawal, and feelings of ineffectiveness. "These patients are not great adventurers," she noted. "They can be bright and accomplishing a lot in school, but inside, they are very afraid of confronting the world and are very insecure." Other characteristics include limited social spontaneity, restrained emotional expression, dependency, maturity fears, depression, and sexual disinterest.
Physical signs can include hypotension, hypothermia, and bradycardia. Those who binge eat and then vomit often present with tooth erosion, poor gum hygiene, swollen parotid glands "so they look like a chipmunk," and abrasions and scars on the dorsum of hands. Other serious long-term consequences of the illness include osteopenia and osteoporosis. "Once a child loses calcium in bones during their development, that can never be replaced; it puts them at risk for fractures in later life," Dr. Halmi said. "What you can do through nutritional rehabilitation is to prevent further mineral loss from the bones."
Certain serum chemistry tests can help you confirm a diagnosis of anorexia nervosa. Leukopenia with relative lymphocytosis is common. "You also want to measure their serum amylase, because if they’re vomiting, most of the time their serum amylase levels will be elevated," she said. In addition, mild metabolic acidosis is suggestive of laxative abuse. Elevated hepatic enzyme levels and hypercholesterolemia may be present, and elevated blood urea nitrogen levels indicate dehydration.
Dr. Halmi underscored the importance of checking for abuse of stimulants, including amphetamines, caffeine, and nicotine, for weight control. Patients who binge and purge "have a high incidence of drug abuse with alcohol or cocaine," she added. "Ipecac may be used to induce vomiting. That can be especially harmful, because ipecac can cause myocardial damage that is irreversible."
According to Dr. Halmi, the mortality for patients with anorexia nervosa is estimated to be about 7% at 10 years. At 30 years the mortality jumps to 18%-21%. The crude mortality is about 5% per decade. "In the long term, 50% of patients will recover, but about 25% will die of their illness, and about 25% will remain chronically ill for a long period of time," she said.
Few randomized, controlled trials of treatment for the illness exist, principally because it’s difficult to enroll an adequate sample size into such studies. "Also, anorexia nervosa patients are resistant to treatment, so to get them to enter a treatment trial is a real effort," she said. "In addition, medical complications can require withdrawal from treatment protocols."
Dr. Halmi described ideal treatment of patients with the illness as multifocused with compatible team personnel. Medical management is necessary, along with nutritional rehabilitation, psychotherapy, and family therapy, which is essential for adolescents, she said. "I emphasize this because once patients reach age 18, they are legal citizens, and you cannot force them to receive treatment unless they are near death. They have to be very ill before you can convince a judge they need to be committed. The longer they stay in their behavior of losing weight in their malnutrition state, the less likely they are to recover. People who are chronically underweight for longer than 6 years do not recover from this illness. Therefore, it’s important to diagnose this disorder and get them into treatment with an experienced team."
Limited positive evidence exists for cognitive-behavioral therapy for adults and family-based therapy for adolescents. Behavioral family therapy has been shown to be effective in five randomized trials. "Parents with high expressed emotion or criticism will do better with their anorectic adolescents in separated rather than whole family therapy," Dr. Halmi said. "In the short term, 10 sessions over 6 months is effective for intact families and patients low in obsessive-compulsive features."
Although about 20 randomized controlled studies of pharmacologic treatment have been performed to date, no "grade A" evidence exists for using medication in patients with anorexia nervosa. Category B evidence supports the use of 100 mg zinc gluconate or 14 mg elemental zinc per day for 2 months or olanzapine 5-15 mg/day. "The main problem in using olanzapine is compliance," Dr. Halmi said.
Negative evidence exists for prescribing antidepressants for patients with this illness, and insufficient evidence exists for using cyproheptadine up to 24 mg/day, but Dr. Halmi said she has found that some patients benefit from cyproheptadine. "It mainly acts not by increasing appetite, but by slightly reducing body movements," she said.
Dr. Halmi said she had no relevant financial conflicts to disclose.
EXPERT ANALYSIS AT THE NPA ANNUAL PSYCHOPHARMACOLOGY UPDATE
Consider four factors in refractory MDD
LAS VEGAS – Despite your best efforts at treating patients newly diagnosed with major depressive disorder, only about 1 in 3 patients achieves remission on the first antidepressant and almost 50% subsequently relapse.
"Our work is cut out for is," Dr. Jonathan E. Alpert said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Factors associated with nonremission in major depressive disorder (MDD) include a history of chronic or recurrent depression; anxious, melancholic, or psychotic features; psychiatric or general medical comorbidity; minority ethnic/racial status; and lower quality of life and function prior to treatment. When a patient fails to remit, Dr. Alpert recommends a checklist of four basic factors to consider before rushing to the next medication or to the next form of psychotherapy.
"It’s important to step back for a moment and recheck what you think you know about that particular patient," said Dr. Alpert, associate chief of psychiatry for clinical services at Massachusetts General Hospital (MGH), Boston.
One factor on the checklist is adherence. Some patients – and sometimes their significant others – are ambivalent about pursuing depression treatment, which could interfere with adherence. "Other patients are confused about the instructions we’ve given them, or they might have cognitive problems that make it difficult for them to stick with the complex regimens we might be prescribing," he explained. "Access to health care and cost of medications can also play a role."
Another factor on the checklist is to be sure of your primary diagnosis. Is it MDD, or is it MDD with psychotic features? Is it bipolar disorder or mood dysregulation in the context of personality disorder? "It can be difficult to separate these," he said.
A third factor on the checklist is to assess for comorbidities such as substance abuse; obsessive-compulsive disorder; posttraumatic stress disorder; and general medical conditions that can mimic MDD symptoms, such as hypothyroidism.
A fourth factor to consider is drug-drug interactions and pharmacokinetics. For example, rapid/fast metabolizers and smokers "may require high doses of medication to achieve a benefit," said Dr. Alpert, who also serves as associate director of the MGH Depression Clinical and Research Program.
After you’ve run through the checklist and you’re confident that a patient has MDD, consider switch, augmentation, and combination strategies to improve response. "Typically we switch from one antidepressant to another in the setting of nonresponse or intolerance to the first agent," he said. "It’s been difficult to see differential effects of different classes of antidepressants. There are some limited data that show the inferiority of tricyclic antidepressants compared with monoamine oxidase inhibitors in patients with atypical features – the kind of depression characterized by pronounced rejection, sensitivity, and mood reactivity."
Dr. Alpert noted that some data support selective norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants as being superior to selective serotonin reuptake inhibitors (SSRIs) in MDD complicated by comorbid pain syndrome such as fibromyalgia. "Bupropion is clearly better than SSRIs and SNRIs for MDD with antidepressant-related sexual dysfunction, nicotine dependence, or ADHD," he said. "Consider broad-spectrum agents such as clomipramine in the setting of persistent refractory depression."
For patients who have only achieved partial response to an antidepressant, consider augmenting with a nonantidepressant such as atypical antipsychotics; dopamine agonists and psychostimulants; lithium; thyroid (T3); buspirone; and natural agents such as l-methylfolate, S-adenosyl-l-methionine (SAMe), creatinine, and omega-3 fatty acids.
Another strategy is to combine antidepressants together in the context of partial response and tolerability of the initial agent. Examples of combination therapy include an SSRI or SNRI plus bupropion, or an SNRI plus mirtazapine.
As for future directions in the psychopharmacology of depression, important recent targets in drug development include mitochondrial function, inflammation processes, and neurogenesis. "Non-monoaminergic mechanisms including kappa and NK1 antagonists and a range of glutamatergic agents are a continued and growing focus," Dr. Alpert concluded. "Rapid-acting antidepressants such as intravenous ketamine and scopolamine promise novel strategies for jump-starting treatment."
Dr. Alpert said he had no relevant financial conflicts to disclose.
LAS VEGAS – Despite your best efforts at treating patients newly diagnosed with major depressive disorder, only about 1 in 3 patients achieves remission on the first antidepressant and almost 50% subsequently relapse.
"Our work is cut out for is," Dr. Jonathan E. Alpert said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Factors associated with nonremission in major depressive disorder (MDD) include a history of chronic or recurrent depression; anxious, melancholic, or psychotic features; psychiatric or general medical comorbidity; minority ethnic/racial status; and lower quality of life and function prior to treatment. When a patient fails to remit, Dr. Alpert recommends a checklist of four basic factors to consider before rushing to the next medication or to the next form of psychotherapy.
"It’s important to step back for a moment and recheck what you think you know about that particular patient," said Dr. Alpert, associate chief of psychiatry for clinical services at Massachusetts General Hospital (MGH), Boston.
One factor on the checklist is adherence. Some patients – and sometimes their significant others – are ambivalent about pursuing depression treatment, which could interfere with adherence. "Other patients are confused about the instructions we’ve given them, or they might have cognitive problems that make it difficult for them to stick with the complex regimens we might be prescribing," he explained. "Access to health care and cost of medications can also play a role."
Another factor on the checklist is to be sure of your primary diagnosis. Is it MDD, or is it MDD with psychotic features? Is it bipolar disorder or mood dysregulation in the context of personality disorder? "It can be difficult to separate these," he said.
A third factor on the checklist is to assess for comorbidities such as substance abuse; obsessive-compulsive disorder; posttraumatic stress disorder; and general medical conditions that can mimic MDD symptoms, such as hypothyroidism.
A fourth factor to consider is drug-drug interactions and pharmacokinetics. For example, rapid/fast metabolizers and smokers "may require high doses of medication to achieve a benefit," said Dr. Alpert, who also serves as associate director of the MGH Depression Clinical and Research Program.
After you’ve run through the checklist and you’re confident that a patient has MDD, consider switch, augmentation, and combination strategies to improve response. "Typically we switch from one antidepressant to another in the setting of nonresponse or intolerance to the first agent," he said. "It’s been difficult to see differential effects of different classes of antidepressants. There are some limited data that show the inferiority of tricyclic antidepressants compared with monoamine oxidase inhibitors in patients with atypical features – the kind of depression characterized by pronounced rejection, sensitivity, and mood reactivity."
Dr. Alpert noted that some data support selective norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants as being superior to selective serotonin reuptake inhibitors (SSRIs) in MDD complicated by comorbid pain syndrome such as fibromyalgia. "Bupropion is clearly better than SSRIs and SNRIs for MDD with antidepressant-related sexual dysfunction, nicotine dependence, or ADHD," he said. "Consider broad-spectrum agents such as clomipramine in the setting of persistent refractory depression."
For patients who have only achieved partial response to an antidepressant, consider augmenting with a nonantidepressant such as atypical antipsychotics; dopamine agonists and psychostimulants; lithium; thyroid (T3); buspirone; and natural agents such as l-methylfolate, S-adenosyl-l-methionine (SAMe), creatinine, and omega-3 fatty acids.
Another strategy is to combine antidepressants together in the context of partial response and tolerability of the initial agent. Examples of combination therapy include an SSRI or SNRI plus bupropion, or an SNRI plus mirtazapine.
As for future directions in the psychopharmacology of depression, important recent targets in drug development include mitochondrial function, inflammation processes, and neurogenesis. "Non-monoaminergic mechanisms including kappa and NK1 antagonists and a range of glutamatergic agents are a continued and growing focus," Dr. Alpert concluded. "Rapid-acting antidepressants such as intravenous ketamine and scopolamine promise novel strategies for jump-starting treatment."
Dr. Alpert said he had no relevant financial conflicts to disclose.
LAS VEGAS – Despite your best efforts at treating patients newly diagnosed with major depressive disorder, only about 1 in 3 patients achieves remission on the first antidepressant and almost 50% subsequently relapse.
"Our work is cut out for is," Dr. Jonathan E. Alpert said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Factors associated with nonremission in major depressive disorder (MDD) include a history of chronic or recurrent depression; anxious, melancholic, or psychotic features; psychiatric or general medical comorbidity; minority ethnic/racial status; and lower quality of life and function prior to treatment. When a patient fails to remit, Dr. Alpert recommends a checklist of four basic factors to consider before rushing to the next medication or to the next form of psychotherapy.
"It’s important to step back for a moment and recheck what you think you know about that particular patient," said Dr. Alpert, associate chief of psychiatry for clinical services at Massachusetts General Hospital (MGH), Boston.
One factor on the checklist is adherence. Some patients – and sometimes their significant others – are ambivalent about pursuing depression treatment, which could interfere with adherence. "Other patients are confused about the instructions we’ve given them, or they might have cognitive problems that make it difficult for them to stick with the complex regimens we might be prescribing," he explained. "Access to health care and cost of medications can also play a role."
Another factor on the checklist is to be sure of your primary diagnosis. Is it MDD, or is it MDD with psychotic features? Is it bipolar disorder or mood dysregulation in the context of personality disorder? "It can be difficult to separate these," he said.
A third factor on the checklist is to assess for comorbidities such as substance abuse; obsessive-compulsive disorder; posttraumatic stress disorder; and general medical conditions that can mimic MDD symptoms, such as hypothyroidism.
A fourth factor to consider is drug-drug interactions and pharmacokinetics. For example, rapid/fast metabolizers and smokers "may require high doses of medication to achieve a benefit," said Dr. Alpert, who also serves as associate director of the MGH Depression Clinical and Research Program.
After you’ve run through the checklist and you’re confident that a patient has MDD, consider switch, augmentation, and combination strategies to improve response. "Typically we switch from one antidepressant to another in the setting of nonresponse or intolerance to the first agent," he said. "It’s been difficult to see differential effects of different classes of antidepressants. There are some limited data that show the inferiority of tricyclic antidepressants compared with monoamine oxidase inhibitors in patients with atypical features – the kind of depression characterized by pronounced rejection, sensitivity, and mood reactivity."
Dr. Alpert noted that some data support selective norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants as being superior to selective serotonin reuptake inhibitors (SSRIs) in MDD complicated by comorbid pain syndrome such as fibromyalgia. "Bupropion is clearly better than SSRIs and SNRIs for MDD with antidepressant-related sexual dysfunction, nicotine dependence, or ADHD," he said. "Consider broad-spectrum agents such as clomipramine in the setting of persistent refractory depression."
For patients who have only achieved partial response to an antidepressant, consider augmenting with a nonantidepressant such as atypical antipsychotics; dopamine agonists and psychostimulants; lithium; thyroid (T3); buspirone; and natural agents such as l-methylfolate, S-adenosyl-l-methionine (SAMe), creatinine, and omega-3 fatty acids.
Another strategy is to combine antidepressants together in the context of partial response and tolerability of the initial agent. Examples of combination therapy include an SSRI or SNRI plus bupropion, or an SNRI plus mirtazapine.
As for future directions in the psychopharmacology of depression, important recent targets in drug development include mitochondrial function, inflammation processes, and neurogenesis. "Non-monoaminergic mechanisms including kappa and NK1 antagonists and a range of glutamatergic agents are a continued and growing focus," Dr. Alpert concluded. "Rapid-acting antidepressants such as intravenous ketamine and scopolamine promise novel strategies for jump-starting treatment."
Dr. Alpert said he had no relevant financial conflicts to disclose.
EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE
Alzheimer’s treatment requires ‘multiple shots on goal’ approach
LAS VEGAS – With the exception of memantine, about 30 clinical trials of agents intended to halt the progression of Alzheimer’s disease have failed in the past decade.
"We’ve attacked every process you can think of in the amyloid cascade, but it’s possible that maybe these were just the wrong medications," Dr. Dylan P. Wint said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
According to retrospective analyses, 20-30% of people diagnosed with Alzheimer’s disease (AD) turned out to not have the condition, said Dr. Wint, director of the fellowship in behavioral neurology and neuropsychiatry at the Las Vegas–based Cleveland Clinic’s Lou Ruvo Center for Brain Health. This suggests that "we may be doing trials on the wrong patients because of inadequate identification of the underlying pathology," he said. The focus on beta-amyloid also could be misguided, he suggested. "There is a strong possibility that we have the wrong hypothesis. Maybe attacking the amyloid is not going to make a dent in what happens with the disease overall. It turns out that amyloid pathology doesn’t correlate very well with symptoms of AD. Tau is much more associated with AD symptoms in terms of its distribution, compared with amyloid."
On the other hand, Dr. Wint pointed out that genetic mutations that cause Alzheimer’s disease are related to amyloid processing. Other processes that could have an impact on AD and warrant investigation include quality of cerebral cells, viability of neurons, and outgrowth of neurites, he added.
Promising AD biomarkers being studied in clinical trials such as brain imaging techniques, blood tests, and genetic-risk profiling might help clinicians identify the disease before symptoms start. "Biomarkers can help us to [recruit] patients who are more suited for clinical trials," added Dr. Wint, who is also director of education in neurodegeneration at the center. "They can help us verify the disease process and measure the severity of the disease – not just symptoms – and we can classify patients by the biomarker."
Emerging AD therapies in the pipeline can be classified as symptomatic (targeting cognition and behavior), disease-modifying (anti–beta-amyloid, anti-tau, and promoting neuroprotection), and regenerative (reversing the disease with stem cells and growth factors). According to Dr. Wint, disease-modifying treatments currently or recently in phase III trials include solanezumab, gantenerumab, albumin plus immunoglobulin, thalidomide, TRx0237, masitinib, and epigallocatechin gallate. Behavioral management agents in phase III trials include bupropion (targeting apathy), mirtazapine (insomnia), citalopram (agitation), and brexpiprazole (agitation). Meanwhile, cognitive enhancement agents being studied in phase III trials include nasal insulin, caprylic triglyceride, and coconut oil.
Dr. Wint said he and other researchers currently take "a multiple shots on goal approach" to advancing the understanding of AD. "That means trying things from all of these categories," he said. "At the Lou Ruvo Center, we’re looking at diagnosis through blood testing, studying the impact of the oral cancer drug bexarotene on amyloid, medical foods, IV [intravenous] medications, the impact of a magnetic stimulation device on information processing, and brain imaging as a way to diagnose candidates for clinical trials."
Dr. Wint disclosed that he has received speakers fees from Accera and has consulted for Teva Pharmaceutical Industries.
LAS VEGAS – With the exception of memantine, about 30 clinical trials of agents intended to halt the progression of Alzheimer’s disease have failed in the past decade.
"We’ve attacked every process you can think of in the amyloid cascade, but it’s possible that maybe these were just the wrong medications," Dr. Dylan P. Wint said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
According to retrospective analyses, 20-30% of people diagnosed with Alzheimer’s disease (AD) turned out to not have the condition, said Dr. Wint, director of the fellowship in behavioral neurology and neuropsychiatry at the Las Vegas–based Cleveland Clinic’s Lou Ruvo Center for Brain Health. This suggests that "we may be doing trials on the wrong patients because of inadequate identification of the underlying pathology," he said. The focus on beta-amyloid also could be misguided, he suggested. "There is a strong possibility that we have the wrong hypothesis. Maybe attacking the amyloid is not going to make a dent in what happens with the disease overall. It turns out that amyloid pathology doesn’t correlate very well with symptoms of AD. Tau is much more associated with AD symptoms in terms of its distribution, compared with amyloid."
On the other hand, Dr. Wint pointed out that genetic mutations that cause Alzheimer’s disease are related to amyloid processing. Other processes that could have an impact on AD and warrant investigation include quality of cerebral cells, viability of neurons, and outgrowth of neurites, he added.
Promising AD biomarkers being studied in clinical trials such as brain imaging techniques, blood tests, and genetic-risk profiling might help clinicians identify the disease before symptoms start. "Biomarkers can help us to [recruit] patients who are more suited for clinical trials," added Dr. Wint, who is also director of education in neurodegeneration at the center. "They can help us verify the disease process and measure the severity of the disease – not just symptoms – and we can classify patients by the biomarker."
Emerging AD therapies in the pipeline can be classified as symptomatic (targeting cognition and behavior), disease-modifying (anti–beta-amyloid, anti-tau, and promoting neuroprotection), and regenerative (reversing the disease with stem cells and growth factors). According to Dr. Wint, disease-modifying treatments currently or recently in phase III trials include solanezumab, gantenerumab, albumin plus immunoglobulin, thalidomide, TRx0237, masitinib, and epigallocatechin gallate. Behavioral management agents in phase III trials include bupropion (targeting apathy), mirtazapine (insomnia), citalopram (agitation), and brexpiprazole (agitation). Meanwhile, cognitive enhancement agents being studied in phase III trials include nasal insulin, caprylic triglyceride, and coconut oil.
Dr. Wint said he and other researchers currently take "a multiple shots on goal approach" to advancing the understanding of AD. "That means trying things from all of these categories," he said. "At the Lou Ruvo Center, we’re looking at diagnosis through blood testing, studying the impact of the oral cancer drug bexarotene on amyloid, medical foods, IV [intravenous] medications, the impact of a magnetic stimulation device on information processing, and brain imaging as a way to diagnose candidates for clinical trials."
Dr. Wint disclosed that he has received speakers fees from Accera and has consulted for Teva Pharmaceutical Industries.
LAS VEGAS – With the exception of memantine, about 30 clinical trials of agents intended to halt the progression of Alzheimer’s disease have failed in the past decade.
"We’ve attacked every process you can think of in the amyloid cascade, but it’s possible that maybe these were just the wrong medications," Dr. Dylan P. Wint said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
According to retrospective analyses, 20-30% of people diagnosed with Alzheimer’s disease (AD) turned out to not have the condition, said Dr. Wint, director of the fellowship in behavioral neurology and neuropsychiatry at the Las Vegas–based Cleveland Clinic’s Lou Ruvo Center for Brain Health. This suggests that "we may be doing trials on the wrong patients because of inadequate identification of the underlying pathology," he said. The focus on beta-amyloid also could be misguided, he suggested. "There is a strong possibility that we have the wrong hypothesis. Maybe attacking the amyloid is not going to make a dent in what happens with the disease overall. It turns out that amyloid pathology doesn’t correlate very well with symptoms of AD. Tau is much more associated with AD symptoms in terms of its distribution, compared with amyloid."
On the other hand, Dr. Wint pointed out that genetic mutations that cause Alzheimer’s disease are related to amyloid processing. Other processes that could have an impact on AD and warrant investigation include quality of cerebral cells, viability of neurons, and outgrowth of neurites, he added.
Promising AD biomarkers being studied in clinical trials such as brain imaging techniques, blood tests, and genetic-risk profiling might help clinicians identify the disease before symptoms start. "Biomarkers can help us to [recruit] patients who are more suited for clinical trials," added Dr. Wint, who is also director of education in neurodegeneration at the center. "They can help us verify the disease process and measure the severity of the disease – not just symptoms – and we can classify patients by the biomarker."
Emerging AD therapies in the pipeline can be classified as symptomatic (targeting cognition and behavior), disease-modifying (anti–beta-amyloid, anti-tau, and promoting neuroprotection), and regenerative (reversing the disease with stem cells and growth factors). According to Dr. Wint, disease-modifying treatments currently or recently in phase III trials include solanezumab, gantenerumab, albumin plus immunoglobulin, thalidomide, TRx0237, masitinib, and epigallocatechin gallate. Behavioral management agents in phase III trials include bupropion (targeting apathy), mirtazapine (insomnia), citalopram (agitation), and brexpiprazole (agitation). Meanwhile, cognitive enhancement agents being studied in phase III trials include nasal insulin, caprylic triglyceride, and coconut oil.
Dr. Wint said he and other researchers currently take "a multiple shots on goal approach" to advancing the understanding of AD. "That means trying things from all of these categories," he said. "At the Lou Ruvo Center, we’re looking at diagnosis through blood testing, studying the impact of the oral cancer drug bexarotene on amyloid, medical foods, IV [intravenous] medications, the impact of a magnetic stimulation device on information processing, and brain imaging as a way to diagnose candidates for clinical trials."
Dr. Wint disclosed that he has received speakers fees from Accera and has consulted for Teva Pharmaceutical Industries.
EXPERT ANALYSIS AT THE NPA ANNUAL PSYCHOPHARMACOLOGY UPDATE
Axis I ailments common in hypersexual disorder
LAS VEGAS – A growing body of evidence suggests that a high proportion of men with hypersexual disorder have an axis I psychiatric comorbidity such as attention-deficit/hyperactivity disorder, an association that can easily fly under a clinician’s radar.
"ADHD is very prominent in men with hypersexual disorder who come to see me now, occurring about 45% of the time," Dr. Martin Kafka said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "I spend half of my time trying to get authorizations for them to be prescribed stimulants."
Men with ADHD tend to "look for something novel when they’re feeling dysphoric affect like boredom or when they’re depressed," continued Dr. Kafka, clinical associate professor of psychiatry at Harvard Medical School, Boston, and an authority on hypersexual disorder (HD). "They procrastinate, so when they’re facing stressful events they escape through their sexual behavior. Pornography is very tempting, because it can be viewed with just the click of a button."
He based his remarks on an analysis of medical records from about 150 HD patients he’s treated in recent years, with a goal of expanding that data set to at least 300. Previous studies he published from 1994 to 2002 suggested that the association between HD and ADHD ranged from 17% to 19%. Those studies also found that dysthymia was the most common coexisting axis I disorder in HD patients, occurring 61%-62% of the time, followed by alcohol abuse (25%-39%) and social phobia (22%-25%).
In Dr. Kafka’s current clinical practice, about 26% of men with HD that he counsels also have bipolar spectrum disorder. "What’s interesting is that this tends to occur in patients with cyclothymic disorder or bipolar disorder not otherwise specified," he said. "It’s the ones who have hypomanias lasting 1-2 days, but repetitively, who have a family history of the illness. In community samples, about 5% of the population meets criteria for hypomania if you shorten the duration to 1-2 days. We really need to be sensitive about brief, recurrent hypomanias and things like cyclothymic disorder, where you’re not depressed for that long."
Though one hallmark symptom of major depressive disorder (MDD) is decreased sexual interest, a small body of literature suggests that the opposite might be true. "This sounds counterintuitive, but subgroups of patients with MDD can have increased sexual behavior," Dr. Kafka said. "Some can have chronically increased sexual behavior." In one 1993 study of cognitive therapy in 40 subjects who were having problems with sexual arousal, 28 got better. The 12 who didn’t get better had chronic low-grade depression" (Arch. Gen. Psychiatry 1993;50:24-30).
Other investigators have reported that when men are depressed, they are more likely to respond to dysphoric affect through action and impulsivity (Arch. Sexual Behav. 2003; 32:217-30). "So even though it’s counterintuitive, depressive disorders can be associated with hypersexuality," Dr. Kafka said.
Treatment of axis I disorders, when executed properly, can positively affect outcomes for patients with HD. "Consider doing a thorough diagnostic evaluation," Dr. Kafka advised. "If they’re not getting better with nonpharmacological treatments, or their behavior is endangering them, then medications could be indicated." He went on to note that the medical model "goes a long way to destigmatize behavior in patients with HD. Yes, there are people who do immoral acts. Promiscuous behavior is an immoral act. But it could be embedded in a psychiatric disorder, which makes it much more complex. It makes it much more understandable; it can destigmatize the person. The person is not just a philanderer; the person is somebody who has an affliction, whose symptom is philandering. They will connect with you if you say this is a medical psychiatric disorder and not just a moral issue."
Though no controlled studies exist on treatment strategies for HD, Dr. Kafka recommended integrating psychiatric diagnosis into the treatment of HD. He also recommended proactive communication with other mental health professionals in helping derive "a good diagnostic picture" of certain patients and educating them about subthreshold adult manifestations of psychiatric diagnoses. "Of course, they can’t really help you with identifying bipolar spectrum disorder or ADHD unless they’re educated about it, but it’s helpful when a psychotherapist tells you that a patient looked hypomanic to him," Dr. Kafka explained. "The next time you see that patient, you might want to ask about that."
He also recommended educating HD patients as much as possible about their illness from resources such as the Society for the Advancement of Sexual Health (www.sash.net) "because these are chronic, early-onset disorders. They’re going to have them for the rest of their lives. Unless they understand them, they’re going to use medication inappropriately, they’re not going to be as treatment compliant and collaborative, and they’re going to relapse."
As to treatment approaches for HD itself, Dr. Kafka recommended a "here and now" approach that involves external interventions to limit access to computers and smart phones, such as phone block, Internet filters with kept passwords, moving the computer to a more public location, changing Internet service providers, and removing credit cards. He acknowledged that disclosing HD to an unsuspecting spouse can be "a minefield. Unless a spouse is prepared to find out about this, it’s devastating, because this is a secret disorder. Many times the spouse has no clue. I’m not going to say don’t tell the spouse, I’m going to say be very careful with your patient about what might be a strategy and when a spouse should find out. When the spouse finds out, it’s important that the spouse be in treatment, that they know how to get some help."
Frequent 12-step meetings that include daily contact with a sponsor are typically indicated for patients with HD, he added, along with individual psychotherapy and some cognitive-behavioral therapy.
"Hypersexuality is a dimension of human behavior; it can be treated," Dr. Kafka concluded. "The psychiatrist is an important player in all this."
Dr. Kafka said that he had no relevant financial conflicts to disclose.
LAS VEGAS – A growing body of evidence suggests that a high proportion of men with hypersexual disorder have an axis I psychiatric comorbidity such as attention-deficit/hyperactivity disorder, an association that can easily fly under a clinician’s radar.
"ADHD is very prominent in men with hypersexual disorder who come to see me now, occurring about 45% of the time," Dr. Martin Kafka said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "I spend half of my time trying to get authorizations for them to be prescribed stimulants."
Men with ADHD tend to "look for something novel when they’re feeling dysphoric affect like boredom or when they’re depressed," continued Dr. Kafka, clinical associate professor of psychiatry at Harvard Medical School, Boston, and an authority on hypersexual disorder (HD). "They procrastinate, so when they’re facing stressful events they escape through their sexual behavior. Pornography is very tempting, because it can be viewed with just the click of a button."
He based his remarks on an analysis of medical records from about 150 HD patients he’s treated in recent years, with a goal of expanding that data set to at least 300. Previous studies he published from 1994 to 2002 suggested that the association between HD and ADHD ranged from 17% to 19%. Those studies also found that dysthymia was the most common coexisting axis I disorder in HD patients, occurring 61%-62% of the time, followed by alcohol abuse (25%-39%) and social phobia (22%-25%).
In Dr. Kafka’s current clinical practice, about 26% of men with HD that he counsels also have bipolar spectrum disorder. "What’s interesting is that this tends to occur in patients with cyclothymic disorder or bipolar disorder not otherwise specified," he said. "It’s the ones who have hypomanias lasting 1-2 days, but repetitively, who have a family history of the illness. In community samples, about 5% of the population meets criteria for hypomania if you shorten the duration to 1-2 days. We really need to be sensitive about brief, recurrent hypomanias and things like cyclothymic disorder, where you’re not depressed for that long."
Though one hallmark symptom of major depressive disorder (MDD) is decreased sexual interest, a small body of literature suggests that the opposite might be true. "This sounds counterintuitive, but subgroups of patients with MDD can have increased sexual behavior," Dr. Kafka said. "Some can have chronically increased sexual behavior." In one 1993 study of cognitive therapy in 40 subjects who were having problems with sexual arousal, 28 got better. The 12 who didn’t get better had chronic low-grade depression" (Arch. Gen. Psychiatry 1993;50:24-30).
Other investigators have reported that when men are depressed, they are more likely to respond to dysphoric affect through action and impulsivity (Arch. Sexual Behav. 2003; 32:217-30). "So even though it’s counterintuitive, depressive disorders can be associated with hypersexuality," Dr. Kafka said.
Treatment of axis I disorders, when executed properly, can positively affect outcomes for patients with HD. "Consider doing a thorough diagnostic evaluation," Dr. Kafka advised. "If they’re not getting better with nonpharmacological treatments, or their behavior is endangering them, then medications could be indicated." He went on to note that the medical model "goes a long way to destigmatize behavior in patients with HD. Yes, there are people who do immoral acts. Promiscuous behavior is an immoral act. But it could be embedded in a psychiatric disorder, which makes it much more complex. It makes it much more understandable; it can destigmatize the person. The person is not just a philanderer; the person is somebody who has an affliction, whose symptom is philandering. They will connect with you if you say this is a medical psychiatric disorder and not just a moral issue."
Though no controlled studies exist on treatment strategies for HD, Dr. Kafka recommended integrating psychiatric diagnosis into the treatment of HD. He also recommended proactive communication with other mental health professionals in helping derive "a good diagnostic picture" of certain patients and educating them about subthreshold adult manifestations of psychiatric diagnoses. "Of course, they can’t really help you with identifying bipolar spectrum disorder or ADHD unless they’re educated about it, but it’s helpful when a psychotherapist tells you that a patient looked hypomanic to him," Dr. Kafka explained. "The next time you see that patient, you might want to ask about that."
He also recommended educating HD patients as much as possible about their illness from resources such as the Society for the Advancement of Sexual Health (www.sash.net) "because these are chronic, early-onset disorders. They’re going to have them for the rest of their lives. Unless they understand them, they’re going to use medication inappropriately, they’re not going to be as treatment compliant and collaborative, and they’re going to relapse."
As to treatment approaches for HD itself, Dr. Kafka recommended a "here and now" approach that involves external interventions to limit access to computers and smart phones, such as phone block, Internet filters with kept passwords, moving the computer to a more public location, changing Internet service providers, and removing credit cards. He acknowledged that disclosing HD to an unsuspecting spouse can be "a minefield. Unless a spouse is prepared to find out about this, it’s devastating, because this is a secret disorder. Many times the spouse has no clue. I’m not going to say don’t tell the spouse, I’m going to say be very careful with your patient about what might be a strategy and when a spouse should find out. When the spouse finds out, it’s important that the spouse be in treatment, that they know how to get some help."
Frequent 12-step meetings that include daily contact with a sponsor are typically indicated for patients with HD, he added, along with individual psychotherapy and some cognitive-behavioral therapy.
"Hypersexuality is a dimension of human behavior; it can be treated," Dr. Kafka concluded. "The psychiatrist is an important player in all this."
Dr. Kafka said that he had no relevant financial conflicts to disclose.
LAS VEGAS – A growing body of evidence suggests that a high proportion of men with hypersexual disorder have an axis I psychiatric comorbidity such as attention-deficit/hyperactivity disorder, an association that can easily fly under a clinician’s radar.
"ADHD is very prominent in men with hypersexual disorder who come to see me now, occurring about 45% of the time," Dr. Martin Kafka said at the annual psychopharmacology update held by the Nevada Psychiatric Association. "I spend half of my time trying to get authorizations for them to be prescribed stimulants."
Men with ADHD tend to "look for something novel when they’re feeling dysphoric affect like boredom or when they’re depressed," continued Dr. Kafka, clinical associate professor of psychiatry at Harvard Medical School, Boston, and an authority on hypersexual disorder (HD). "They procrastinate, so when they’re facing stressful events they escape through their sexual behavior. Pornography is very tempting, because it can be viewed with just the click of a button."
He based his remarks on an analysis of medical records from about 150 HD patients he’s treated in recent years, with a goal of expanding that data set to at least 300. Previous studies he published from 1994 to 2002 suggested that the association between HD and ADHD ranged from 17% to 19%. Those studies also found that dysthymia was the most common coexisting axis I disorder in HD patients, occurring 61%-62% of the time, followed by alcohol abuse (25%-39%) and social phobia (22%-25%).
In Dr. Kafka’s current clinical practice, about 26% of men with HD that he counsels also have bipolar spectrum disorder. "What’s interesting is that this tends to occur in patients with cyclothymic disorder or bipolar disorder not otherwise specified," he said. "It’s the ones who have hypomanias lasting 1-2 days, but repetitively, who have a family history of the illness. In community samples, about 5% of the population meets criteria for hypomania if you shorten the duration to 1-2 days. We really need to be sensitive about brief, recurrent hypomanias and things like cyclothymic disorder, where you’re not depressed for that long."
Though one hallmark symptom of major depressive disorder (MDD) is decreased sexual interest, a small body of literature suggests that the opposite might be true. "This sounds counterintuitive, but subgroups of patients with MDD can have increased sexual behavior," Dr. Kafka said. "Some can have chronically increased sexual behavior." In one 1993 study of cognitive therapy in 40 subjects who were having problems with sexual arousal, 28 got better. The 12 who didn’t get better had chronic low-grade depression" (Arch. Gen. Psychiatry 1993;50:24-30).
Other investigators have reported that when men are depressed, they are more likely to respond to dysphoric affect through action and impulsivity (Arch. Sexual Behav. 2003; 32:217-30). "So even though it’s counterintuitive, depressive disorders can be associated with hypersexuality," Dr. Kafka said.
Treatment of axis I disorders, when executed properly, can positively affect outcomes for patients with HD. "Consider doing a thorough diagnostic evaluation," Dr. Kafka advised. "If they’re not getting better with nonpharmacological treatments, or their behavior is endangering them, then medications could be indicated." He went on to note that the medical model "goes a long way to destigmatize behavior in patients with HD. Yes, there are people who do immoral acts. Promiscuous behavior is an immoral act. But it could be embedded in a psychiatric disorder, which makes it much more complex. It makes it much more understandable; it can destigmatize the person. The person is not just a philanderer; the person is somebody who has an affliction, whose symptom is philandering. They will connect with you if you say this is a medical psychiatric disorder and not just a moral issue."
Though no controlled studies exist on treatment strategies for HD, Dr. Kafka recommended integrating psychiatric diagnosis into the treatment of HD. He also recommended proactive communication with other mental health professionals in helping derive "a good diagnostic picture" of certain patients and educating them about subthreshold adult manifestations of psychiatric diagnoses. "Of course, they can’t really help you with identifying bipolar spectrum disorder or ADHD unless they’re educated about it, but it’s helpful when a psychotherapist tells you that a patient looked hypomanic to him," Dr. Kafka explained. "The next time you see that patient, you might want to ask about that."
He also recommended educating HD patients as much as possible about their illness from resources such as the Society for the Advancement of Sexual Health (www.sash.net) "because these are chronic, early-onset disorders. They’re going to have them for the rest of their lives. Unless they understand them, they’re going to use medication inappropriately, they’re not going to be as treatment compliant and collaborative, and they’re going to relapse."
As to treatment approaches for HD itself, Dr. Kafka recommended a "here and now" approach that involves external interventions to limit access to computers and smart phones, such as phone block, Internet filters with kept passwords, moving the computer to a more public location, changing Internet service providers, and removing credit cards. He acknowledged that disclosing HD to an unsuspecting spouse can be "a minefield. Unless a spouse is prepared to find out about this, it’s devastating, because this is a secret disorder. Many times the spouse has no clue. I’m not going to say don’t tell the spouse, I’m going to say be very careful with your patient about what might be a strategy and when a spouse should find out. When the spouse finds out, it’s important that the spouse be in treatment, that they know how to get some help."
Frequent 12-step meetings that include daily contact with a sponsor are typically indicated for patients with HD, he added, along with individual psychotherapy and some cognitive-behavioral therapy.
"Hypersexuality is a dimension of human behavior; it can be treated," Dr. Kafka concluded. "The psychiatrist is an important player in all this."
Dr. Kafka said that he had no relevant financial conflicts to disclose.
EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE
