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Primary care holds key to curbing early-onset colorectal cancer
ESTES PARK, CO – , said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.
The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.
“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.
Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).
“A different clinical and pathological entity”
Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.
“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.
The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.
The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.
Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.
“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”
Vital role for primary care
It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.
“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.
Prompt evaluation of symptoms
In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.
This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.
“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”
Assessing for increased genetic/familial risk
The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.
In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.
The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.
“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.
Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.
“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.
It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.
Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.
Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.
She reported having no financial conflicts regarding her presentation.
ESTES PARK, CO – , said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.
The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.
“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.
Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).
“A different clinical and pathological entity”
Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.
“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.
The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.
The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.
Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.
“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”
Vital role for primary care
It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.
“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.
Prompt evaluation of symptoms
In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.
This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.
“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”
Assessing for increased genetic/familial risk
The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.
In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.
The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.
“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.
Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.
“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.
It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.
Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.
Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.
She reported having no financial conflicts regarding her presentation.
ESTES PARK, CO – , said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.
The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.
“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.
Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).
“A different clinical and pathological entity”
Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.
“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.
The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.
The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.
Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.
“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”
Vital role for primary care
It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.
“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.
Prompt evaluation of symptoms
In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.
This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.
“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”
Assessing for increased genetic/familial risk
The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.
In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.
The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.
“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.
Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.
“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.
It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.
Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.
Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM COLORADO IM
Consider dosing as well as drug choice for anxiety disorders
ESTES PARK, COLO. – The first-line medications for anxiety disorders are the same ones used for depression – the SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) – but the dosing strategies are quite different, Elizabeth L. Lowdermilk, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“We know that folks with anxiety disorders tend to need the higher doses. They just need to get there a little more slowly,” according to Dr. Lowdermilk, a psychiatrist at the university and medical director of outpatient psychiatry at Denver Health.
“The trick is not what drug you use, it’s what dose you started at. For example, when I start sertraline for depression I start it at 50 mg per day. When I start it for anxiety I start it at 25. I just give it a week or 2 at 25 and then I double it to 50. And then I keep going, titrating over 2-3 months to a high or maximum dose,” she explained.
The rapidity of response to the SSRIs and SNRIs is quite different, too. When patients are started on one of these agents as treatment for depression, they can expect that it will take at least 4-6 weeks and maybe as long as 12 weeks before they experience the full therapeutic effect. Not so when the same drugs are used to treat anxiety disorders.
“The anxiolytic effect seems to be more robust sooner. Really, people start noticing something within the first couple days to a week. And they will keep getting better, which people love,” Dr. Lowdermilk said.
One of the early positive effects of SSRI/SNRI therapy that patients can be advised to be on the lookout for is “the Teflon mind,” she said.
“It’s not that the worried thoughts won’t arise, but they’re going to slide out faster and patients are going to be able to shift their focus back to where they want it to be and move forward,” the psychiatrist explained.
Other positive treatment effects include reductions in irritability, anger, perseverative thoughts, restlessness, and physical tension, along with improved sleep.
How to monitor patient response
The most practical anxiety rating scale for busy primary care physicians with tight office visit scheduling is the seven-item Generalized Anxiety Disorder Assessment, or GAD 7. It can be used repeatedly to follow a patient’s treatment response.
“While technically it is picking up the symptoms of GAD, because there are so many overlapping symptoms in all of the anxiety disorders this is going to give you a sense of whether someone is getting better. It won’t pick up their nightmares if they have PTSD, and it won’t necessarily pick up their checking behaviors if they have obsessive-compulsive disorder – you can ask them quickly about that,” she said.
Augmenting an SSRI/SNRI
Be advised: While some patients with an anxiety disorder will experience complete resolution of symptoms on the maximum approved dose of an SSRI/SNRI, such as 200 mg/day of sertraline (Zoloft), lots of patients will have only a partial response. The next move is not to add a second antidepressant, it’s to augment the high-dose antidepressant the patient is already on with something else. Dr. Lowdermilk highlighted the best and worst strategies:
- Hydroxyzine: This drug, approved by the Food and Drug Administration for treatment of panic attacks at 25-50 mg up to four times per day, has sedating side effects that help with sleep issues.
“We use a lot of this,” Dr. Lowdermilk said.
Hydroxyzine (Vistaril) can be dosed on a fixed schedule or as needed. She strongly favors scheduled dosing. “It’s better to use drugs to reduce anxiety tone, then teach skills to cope with anxiety. As needed treatment subtly teaches patients to take a pill if they have breakthrough symptoms.”
- Buspirone: It takes high doses of this medication to get a robust anxiolytic response. Dr. Lowdermilk recommends starting at 5 mg three times daily and increasing the total daily dose by 15 mg every 2 weeks up to a maximum of 60 mg.
“Buspirone isn’t the strongest medication out there, but it can help. I personally don’t stop until I’m at least at 30 mg per day,” she said.
The drug is especially handy as monotherapy in patients with mild to moderate anxiety who can’t tolerate serotonergic medications well. Also, at higher doses buspirone (Buspar) may reduce the sexual side effects of a concomitant serotonergic agent.
- Gabapentin: Dr. Lowdermilk often turns to this drug off label as an SSRI/SNRI augmentation strategy, starting at 100-300 mg three times daily and increasing over the same time frame as for neuropathic pain up to a maximum total daily dose of 3,600 mg. Like hydroxyzine, it helps with sleep.
- Atypical antipsychotics: Reserve these for patients with an inadequate response to maximum-dose SSRI/SNRI. There is some evidence of efficacy for low-dose risperidone (Risperdal) at 1-2 mg/day, quetiapine(Seroquel) at 50-100 mg, and aripiprazole (Abilify) at 2-5 mg. Because of the risks of metabolic side effects and tardive dyskinesia, it’s best to evaluate the drug’s effectiveness after 2-4 weeks and consider stopping if there is no clinical improvement.
- Benzodiazepines: Yes, they are approved for treatment of anxiety disorders. Nevertheless, Dr. Lowdermilk advises against their as routine practice.
“I want to acknowledge that they really do work for anxiety and there are times you might want to consider them. But we are almost never initiating benzodiazepines anymore. We are learning that they cause more problems than not. What I’ve found over the years is short bursts of use are not short. Patients tend to come back and want more,” according to the psychiatrist.
She is not convinced about the claimed link to dementia, but she does believe long-term use of benzodiazepines is associated with memory and balance problems as well as slowed reaction time. If they are going to be used to treat anxiety disorders, it’s best to turn to a longer-acting agent such as clonazepam (Klonopin) or extended-release alprazolam (Xanax XR), which keep the anxiety tone down without producing the euphoria of short-acting benzodiazepines.
- Behavioral therapies: “I really do think that the combination of medication and behavioral therapy is the best approach,” Dr. Lowdermilk said.
Consider referring patients with a problematic anxiety disorder to a behavioral therapist skilled in cognitive behavioral therapy, exposure therapy, response prevention therapy, or eye movement desensitization and reprocessing.
She reported having no financial conflicts regarding her presentation.
ESTES PARK, COLO. – The first-line medications for anxiety disorders are the same ones used for depression – the SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) – but the dosing strategies are quite different, Elizabeth L. Lowdermilk, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“We know that folks with anxiety disorders tend to need the higher doses. They just need to get there a little more slowly,” according to Dr. Lowdermilk, a psychiatrist at the university and medical director of outpatient psychiatry at Denver Health.
“The trick is not what drug you use, it’s what dose you started at. For example, when I start sertraline for depression I start it at 50 mg per day. When I start it for anxiety I start it at 25. I just give it a week or 2 at 25 and then I double it to 50. And then I keep going, titrating over 2-3 months to a high or maximum dose,” she explained.
The rapidity of response to the SSRIs and SNRIs is quite different, too. When patients are started on one of these agents as treatment for depression, they can expect that it will take at least 4-6 weeks and maybe as long as 12 weeks before they experience the full therapeutic effect. Not so when the same drugs are used to treat anxiety disorders.
“The anxiolytic effect seems to be more robust sooner. Really, people start noticing something within the first couple days to a week. And they will keep getting better, which people love,” Dr. Lowdermilk said.
One of the early positive effects of SSRI/SNRI therapy that patients can be advised to be on the lookout for is “the Teflon mind,” she said.
“It’s not that the worried thoughts won’t arise, but they’re going to slide out faster and patients are going to be able to shift their focus back to where they want it to be and move forward,” the psychiatrist explained.
Other positive treatment effects include reductions in irritability, anger, perseverative thoughts, restlessness, and physical tension, along with improved sleep.
How to monitor patient response
The most practical anxiety rating scale for busy primary care physicians with tight office visit scheduling is the seven-item Generalized Anxiety Disorder Assessment, or GAD 7. It can be used repeatedly to follow a patient’s treatment response.
“While technically it is picking up the symptoms of GAD, because there are so many overlapping symptoms in all of the anxiety disorders this is going to give you a sense of whether someone is getting better. It won’t pick up their nightmares if they have PTSD, and it won’t necessarily pick up their checking behaviors if they have obsessive-compulsive disorder – you can ask them quickly about that,” she said.
Augmenting an SSRI/SNRI
Be advised: While some patients with an anxiety disorder will experience complete resolution of symptoms on the maximum approved dose of an SSRI/SNRI, such as 200 mg/day of sertraline (Zoloft), lots of patients will have only a partial response. The next move is not to add a second antidepressant, it’s to augment the high-dose antidepressant the patient is already on with something else. Dr. Lowdermilk highlighted the best and worst strategies:
- Hydroxyzine: This drug, approved by the Food and Drug Administration for treatment of panic attacks at 25-50 mg up to four times per day, has sedating side effects that help with sleep issues.
“We use a lot of this,” Dr. Lowdermilk said.
Hydroxyzine (Vistaril) can be dosed on a fixed schedule or as needed. She strongly favors scheduled dosing. “It’s better to use drugs to reduce anxiety tone, then teach skills to cope with anxiety. As needed treatment subtly teaches patients to take a pill if they have breakthrough symptoms.”
- Buspirone: It takes high doses of this medication to get a robust anxiolytic response. Dr. Lowdermilk recommends starting at 5 mg three times daily and increasing the total daily dose by 15 mg every 2 weeks up to a maximum of 60 mg.
“Buspirone isn’t the strongest medication out there, but it can help. I personally don’t stop until I’m at least at 30 mg per day,” she said.
The drug is especially handy as monotherapy in patients with mild to moderate anxiety who can’t tolerate serotonergic medications well. Also, at higher doses buspirone (Buspar) may reduce the sexual side effects of a concomitant serotonergic agent.
- Gabapentin: Dr. Lowdermilk often turns to this drug off label as an SSRI/SNRI augmentation strategy, starting at 100-300 mg three times daily and increasing over the same time frame as for neuropathic pain up to a maximum total daily dose of 3,600 mg. Like hydroxyzine, it helps with sleep.
- Atypical antipsychotics: Reserve these for patients with an inadequate response to maximum-dose SSRI/SNRI. There is some evidence of efficacy for low-dose risperidone (Risperdal) at 1-2 mg/day, quetiapine(Seroquel) at 50-100 mg, and aripiprazole (Abilify) at 2-5 mg. Because of the risks of metabolic side effects and tardive dyskinesia, it’s best to evaluate the drug’s effectiveness after 2-4 weeks and consider stopping if there is no clinical improvement.
- Benzodiazepines: Yes, they are approved for treatment of anxiety disorders. Nevertheless, Dr. Lowdermilk advises against their as routine practice.
“I want to acknowledge that they really do work for anxiety and there are times you might want to consider them. But we are almost never initiating benzodiazepines anymore. We are learning that they cause more problems than not. What I’ve found over the years is short bursts of use are not short. Patients tend to come back and want more,” according to the psychiatrist.
She is not convinced about the claimed link to dementia, but she does believe long-term use of benzodiazepines is associated with memory and balance problems as well as slowed reaction time. If they are going to be used to treat anxiety disorders, it’s best to turn to a longer-acting agent such as clonazepam (Klonopin) or extended-release alprazolam (Xanax XR), which keep the anxiety tone down without producing the euphoria of short-acting benzodiazepines.
- Behavioral therapies: “I really do think that the combination of medication and behavioral therapy is the best approach,” Dr. Lowdermilk said.
Consider referring patients with a problematic anxiety disorder to a behavioral therapist skilled in cognitive behavioral therapy, exposure therapy, response prevention therapy, or eye movement desensitization and reprocessing.
She reported having no financial conflicts regarding her presentation.
ESTES PARK, COLO. – The first-line medications for anxiety disorders are the same ones used for depression – the SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) – but the dosing strategies are quite different, Elizabeth L. Lowdermilk, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“We know that folks with anxiety disorders tend to need the higher doses. They just need to get there a little more slowly,” according to Dr. Lowdermilk, a psychiatrist at the university and medical director of outpatient psychiatry at Denver Health.
“The trick is not what drug you use, it’s what dose you started at. For example, when I start sertraline for depression I start it at 50 mg per day. When I start it for anxiety I start it at 25. I just give it a week or 2 at 25 and then I double it to 50. And then I keep going, titrating over 2-3 months to a high or maximum dose,” she explained.
The rapidity of response to the SSRIs and SNRIs is quite different, too. When patients are started on one of these agents as treatment for depression, they can expect that it will take at least 4-6 weeks and maybe as long as 12 weeks before they experience the full therapeutic effect. Not so when the same drugs are used to treat anxiety disorders.
“The anxiolytic effect seems to be more robust sooner. Really, people start noticing something within the first couple days to a week. And they will keep getting better, which people love,” Dr. Lowdermilk said.
One of the early positive effects of SSRI/SNRI therapy that patients can be advised to be on the lookout for is “the Teflon mind,” she said.
“It’s not that the worried thoughts won’t arise, but they’re going to slide out faster and patients are going to be able to shift their focus back to where they want it to be and move forward,” the psychiatrist explained.
Other positive treatment effects include reductions in irritability, anger, perseverative thoughts, restlessness, and physical tension, along with improved sleep.
How to monitor patient response
The most practical anxiety rating scale for busy primary care physicians with tight office visit scheduling is the seven-item Generalized Anxiety Disorder Assessment, or GAD 7. It can be used repeatedly to follow a patient’s treatment response.
“While technically it is picking up the symptoms of GAD, because there are so many overlapping symptoms in all of the anxiety disorders this is going to give you a sense of whether someone is getting better. It won’t pick up their nightmares if they have PTSD, and it won’t necessarily pick up their checking behaviors if they have obsessive-compulsive disorder – you can ask them quickly about that,” she said.
Augmenting an SSRI/SNRI
Be advised: While some patients with an anxiety disorder will experience complete resolution of symptoms on the maximum approved dose of an SSRI/SNRI, such as 200 mg/day of sertraline (Zoloft), lots of patients will have only a partial response. The next move is not to add a second antidepressant, it’s to augment the high-dose antidepressant the patient is already on with something else. Dr. Lowdermilk highlighted the best and worst strategies:
- Hydroxyzine: This drug, approved by the Food and Drug Administration for treatment of panic attacks at 25-50 mg up to four times per day, has sedating side effects that help with sleep issues.
“We use a lot of this,” Dr. Lowdermilk said.
Hydroxyzine (Vistaril) can be dosed on a fixed schedule or as needed. She strongly favors scheduled dosing. “It’s better to use drugs to reduce anxiety tone, then teach skills to cope with anxiety. As needed treatment subtly teaches patients to take a pill if they have breakthrough symptoms.”
- Buspirone: It takes high doses of this medication to get a robust anxiolytic response. Dr. Lowdermilk recommends starting at 5 mg three times daily and increasing the total daily dose by 15 mg every 2 weeks up to a maximum of 60 mg.
“Buspirone isn’t the strongest medication out there, but it can help. I personally don’t stop until I’m at least at 30 mg per day,” she said.
The drug is especially handy as monotherapy in patients with mild to moderate anxiety who can’t tolerate serotonergic medications well. Also, at higher doses buspirone (Buspar) may reduce the sexual side effects of a concomitant serotonergic agent.
- Gabapentin: Dr. Lowdermilk often turns to this drug off label as an SSRI/SNRI augmentation strategy, starting at 100-300 mg three times daily and increasing over the same time frame as for neuropathic pain up to a maximum total daily dose of 3,600 mg. Like hydroxyzine, it helps with sleep.
- Atypical antipsychotics: Reserve these for patients with an inadequate response to maximum-dose SSRI/SNRI. There is some evidence of efficacy for low-dose risperidone (Risperdal) at 1-2 mg/day, quetiapine(Seroquel) at 50-100 mg, and aripiprazole (Abilify) at 2-5 mg. Because of the risks of metabolic side effects and tardive dyskinesia, it’s best to evaluate the drug’s effectiveness after 2-4 weeks and consider stopping if there is no clinical improvement.
- Benzodiazepines: Yes, they are approved for treatment of anxiety disorders. Nevertheless, Dr. Lowdermilk advises against their as routine practice.
“I want to acknowledge that they really do work for anxiety and there are times you might want to consider them. But we are almost never initiating benzodiazepines anymore. We are learning that they cause more problems than not. What I’ve found over the years is short bursts of use are not short. Patients tend to come back and want more,” according to the psychiatrist.
She is not convinced about the claimed link to dementia, but she does believe long-term use of benzodiazepines is associated with memory and balance problems as well as slowed reaction time. If they are going to be used to treat anxiety disorders, it’s best to turn to a longer-acting agent such as clonazepam (Klonopin) or extended-release alprazolam (Xanax XR), which keep the anxiety tone down without producing the euphoria of short-acting benzodiazepines.
- Behavioral therapies: “I really do think that the combination of medication and behavioral therapy is the best approach,” Dr. Lowdermilk said.
Consider referring patients with a problematic anxiety disorder to a behavioral therapist skilled in cognitive behavioral therapy, exposure therapy, response prevention therapy, or eye movement desensitization and reprocessing.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM COLORADO IM
Should PCPs take over chronic HCV treatment?
ESTES PARK, COLO. – Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has progressed to the point that it’s time for primary care physicians to take on the treatment of all affected patients who don’t have advanced fibrosis or other complex forms of the disease, Michael Kriss, MD, asserted at a conference on internal medicine sponsored by the University of Colorado.
declared Dr. Kriss, a gastroenterologist at the university.
Referral to a specialist should be reserved for those more complex patients with stage 3 or 4 fibrosis, hepatocellular carcinoma, coinfection with HIV or hepatitis B virus, end-stage organ disease being considered for transplantation, prior exposure to an NS5A inhibitor, or concomitant secondary liver disease, such as nonalcoholic steatohepatitis, he continued.
Treatment of chronic HCV now entails just 8-12 weeks of DAA therapy, with a cure rate greater than 95% and almost no side effects. The costs have come down, too, because of increased competition.
The epidemiology of HCV infection is changing. The opioid epidemic is driving an increased incidence of acute infection, with nearly 34,000 new cases per year, most of which will go on to chronic infection. Moreover, 93% of acutely infected individuals and half of the estimated 3.5 million Americans with chronic HCV are unaware they are infected. The scope of the problem is too big for gastroenterologists and infectious disease specialists to handle alone, according to Dr. Kriss.
Contemporary treatment of HCV involves a 6-step program that’s simpler than that of many of the diseases primary care physicians currently manage.
1) Confirm chronicity by two measurements of HCV RNA obtained 6 months apart.
2) Stage the patient’s fibrosis.
3) Order a baseline cross-sectional ultrasound to exclude cirrhosis or hepatocellular carcinoma, since the fibrosis staging methods aren’t foolproof.
4) Make sure the patient is still positive for HCV RNA prior to therapy.
5) Commence DAA therapy. The simplest regimen is 8 weeks of glecaprevir/pibrentasvir (Mavyret), provided it’s approved by the patient’s insurance.
6) Get a repeat HCV RNA 12 weeks after conclusion of treatment to confirm there is a sustained virologic response.
The critical part is step 2 because that’s how primary care physicians will decide which patients to treat in their office and which to refer to a specialist. Many biomarkers are available, some proprietary and others gratis. Dr. Kriss is particularly partial to the free Fibrosis-4 (Fib-4) calculator, which provides an estimate of the amount of liver scarring based upon the patient’s age, liver enzyme levels, and platelet count.
“This is really a valuable, extremely well-validated tool that any of you can use in your clinic,” he said.
The American Association for the Study of Liver Disease/Infectious Diseases Society of America hepatitis C guidelines state that the nonproprietary biomarker assays are equivalent to transient elastography for staging fibrosis. Those guidelines are an “outstanding” and extremely user-friendly resource for primary care physicians interested in taking on the treatment of chronic HCV, Dr. Kriss added.
In selecting a DAA, another key resource is the HEP Drug Interactions website, which enables physicians to identify potentially problematic drug-drug interactions. The two most important interactions involve statins or proton pump inhibitors.
Recent studies have shown that the benefits of achieving a sustained virologic response include a clinically meaningful regression of advanced fibrosis at 1 year after treatment in roughly half of patients (Dig Dis Sci. 2018 Feb;63[2]:486-92) and a reduced risk of developing hepatocellular carcinoma (Hepatology. 2018 Jun;67[6]:2244-53).
Models of remote consultation pathways to link primary care providers with consultant HCV specialists are being developed. In a study of 600 patients at federally qualified community health centers in Washington, the risk-adjusted cure rate was 90.4% among patients assigned to a nurse practitioner, 87.6% if DAA therapy was prescribed by a primary care physician, and 84.8% if treated by a specialist. Treatment visit adherence followed the same pattern and correlated with cure rates (Ann Intern Med. 2017 Sep 5;167[5]:311-8).
“Patients might be better off seeing someone they know instead of somebody like me who they’re only going to see one time,” Dr. Kriss observed.
Turning to a couple of controversial expansions of DAA into new populations, Dr. Kriss noted that the AASLD/IDSA guidelines state that active intravenous drug use should not be considered a contraindication to HCV therapy.
“Scaling up HCV treatment in persons who inject drugs is necessary to positively impact the HCV epidemic in the U.S. and globally,” according to the guidelines.
This message was recently underscored by the positive results of the seven-country SIMPLIFY trial, in which 12 weeks of velpatasvir-sofosbuvir (Epclusa) in a population of recent IV drug users achieved a 97% cure rate, with only one reinfection in this high-risk population (Lancet Gastroenterol Hepatol. 2018 Mar;3[3]:153-61).
The hottest controversy in hepatology has been whether to place HCV-positive donor organs in HCV-negative recipients.
“This is intentionally giving hepatitis C to the recipient knowing that he can be cured. Because treatment cure rates are so high, I predict this will become the standard of care in the next year or two,” Dr. Kriss said.
He reported having no financial conflicts regarding his presentation.
.
ESTES PARK, COLO. – Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has progressed to the point that it’s time for primary care physicians to take on the treatment of all affected patients who don’t have advanced fibrosis or other complex forms of the disease, Michael Kriss, MD, asserted at a conference on internal medicine sponsored by the University of Colorado.
declared Dr. Kriss, a gastroenterologist at the university.
Referral to a specialist should be reserved for those more complex patients with stage 3 or 4 fibrosis, hepatocellular carcinoma, coinfection with HIV or hepatitis B virus, end-stage organ disease being considered for transplantation, prior exposure to an NS5A inhibitor, or concomitant secondary liver disease, such as nonalcoholic steatohepatitis, he continued.
Treatment of chronic HCV now entails just 8-12 weeks of DAA therapy, with a cure rate greater than 95% and almost no side effects. The costs have come down, too, because of increased competition.
The epidemiology of HCV infection is changing. The opioid epidemic is driving an increased incidence of acute infection, with nearly 34,000 new cases per year, most of which will go on to chronic infection. Moreover, 93% of acutely infected individuals and half of the estimated 3.5 million Americans with chronic HCV are unaware they are infected. The scope of the problem is too big for gastroenterologists and infectious disease specialists to handle alone, according to Dr. Kriss.
Contemporary treatment of HCV involves a 6-step program that’s simpler than that of many of the diseases primary care physicians currently manage.
1) Confirm chronicity by two measurements of HCV RNA obtained 6 months apart.
2) Stage the patient’s fibrosis.
3) Order a baseline cross-sectional ultrasound to exclude cirrhosis or hepatocellular carcinoma, since the fibrosis staging methods aren’t foolproof.
4) Make sure the patient is still positive for HCV RNA prior to therapy.
5) Commence DAA therapy. The simplest regimen is 8 weeks of glecaprevir/pibrentasvir (Mavyret), provided it’s approved by the patient’s insurance.
6) Get a repeat HCV RNA 12 weeks after conclusion of treatment to confirm there is a sustained virologic response.
The critical part is step 2 because that’s how primary care physicians will decide which patients to treat in their office and which to refer to a specialist. Many biomarkers are available, some proprietary and others gratis. Dr. Kriss is particularly partial to the free Fibrosis-4 (Fib-4) calculator, which provides an estimate of the amount of liver scarring based upon the patient’s age, liver enzyme levels, and platelet count.
“This is really a valuable, extremely well-validated tool that any of you can use in your clinic,” he said.
The American Association for the Study of Liver Disease/Infectious Diseases Society of America hepatitis C guidelines state that the nonproprietary biomarker assays are equivalent to transient elastography for staging fibrosis. Those guidelines are an “outstanding” and extremely user-friendly resource for primary care physicians interested in taking on the treatment of chronic HCV, Dr. Kriss added.
In selecting a DAA, another key resource is the HEP Drug Interactions website, which enables physicians to identify potentially problematic drug-drug interactions. The two most important interactions involve statins or proton pump inhibitors.
Recent studies have shown that the benefits of achieving a sustained virologic response include a clinically meaningful regression of advanced fibrosis at 1 year after treatment in roughly half of patients (Dig Dis Sci. 2018 Feb;63[2]:486-92) and a reduced risk of developing hepatocellular carcinoma (Hepatology. 2018 Jun;67[6]:2244-53).
Models of remote consultation pathways to link primary care providers with consultant HCV specialists are being developed. In a study of 600 patients at federally qualified community health centers in Washington, the risk-adjusted cure rate was 90.4% among patients assigned to a nurse practitioner, 87.6% if DAA therapy was prescribed by a primary care physician, and 84.8% if treated by a specialist. Treatment visit adherence followed the same pattern and correlated with cure rates (Ann Intern Med. 2017 Sep 5;167[5]:311-8).
“Patients might be better off seeing someone they know instead of somebody like me who they’re only going to see one time,” Dr. Kriss observed.
Turning to a couple of controversial expansions of DAA into new populations, Dr. Kriss noted that the AASLD/IDSA guidelines state that active intravenous drug use should not be considered a contraindication to HCV therapy.
“Scaling up HCV treatment in persons who inject drugs is necessary to positively impact the HCV epidemic in the U.S. and globally,” according to the guidelines.
This message was recently underscored by the positive results of the seven-country SIMPLIFY trial, in which 12 weeks of velpatasvir-sofosbuvir (Epclusa) in a population of recent IV drug users achieved a 97% cure rate, with only one reinfection in this high-risk population (Lancet Gastroenterol Hepatol. 2018 Mar;3[3]:153-61).
The hottest controversy in hepatology has been whether to place HCV-positive donor organs in HCV-negative recipients.
“This is intentionally giving hepatitis C to the recipient knowing that he can be cured. Because treatment cure rates are so high, I predict this will become the standard of care in the next year or two,” Dr. Kriss said.
He reported having no financial conflicts regarding his presentation.
.
ESTES PARK, COLO. – Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has progressed to the point that it’s time for primary care physicians to take on the treatment of all affected patients who don’t have advanced fibrosis or other complex forms of the disease, Michael Kriss, MD, asserted at a conference on internal medicine sponsored by the University of Colorado.
declared Dr. Kriss, a gastroenterologist at the university.
Referral to a specialist should be reserved for those more complex patients with stage 3 or 4 fibrosis, hepatocellular carcinoma, coinfection with HIV or hepatitis B virus, end-stage organ disease being considered for transplantation, prior exposure to an NS5A inhibitor, or concomitant secondary liver disease, such as nonalcoholic steatohepatitis, he continued.
Treatment of chronic HCV now entails just 8-12 weeks of DAA therapy, with a cure rate greater than 95% and almost no side effects. The costs have come down, too, because of increased competition.
The epidemiology of HCV infection is changing. The opioid epidemic is driving an increased incidence of acute infection, with nearly 34,000 new cases per year, most of which will go on to chronic infection. Moreover, 93% of acutely infected individuals and half of the estimated 3.5 million Americans with chronic HCV are unaware they are infected. The scope of the problem is too big for gastroenterologists and infectious disease specialists to handle alone, according to Dr. Kriss.
Contemporary treatment of HCV involves a 6-step program that’s simpler than that of many of the diseases primary care physicians currently manage.
1) Confirm chronicity by two measurements of HCV RNA obtained 6 months apart.
2) Stage the patient’s fibrosis.
3) Order a baseline cross-sectional ultrasound to exclude cirrhosis or hepatocellular carcinoma, since the fibrosis staging methods aren’t foolproof.
4) Make sure the patient is still positive for HCV RNA prior to therapy.
5) Commence DAA therapy. The simplest regimen is 8 weeks of glecaprevir/pibrentasvir (Mavyret), provided it’s approved by the patient’s insurance.
6) Get a repeat HCV RNA 12 weeks after conclusion of treatment to confirm there is a sustained virologic response.
The critical part is step 2 because that’s how primary care physicians will decide which patients to treat in their office and which to refer to a specialist. Many biomarkers are available, some proprietary and others gratis. Dr. Kriss is particularly partial to the free Fibrosis-4 (Fib-4) calculator, which provides an estimate of the amount of liver scarring based upon the patient’s age, liver enzyme levels, and platelet count.
“This is really a valuable, extremely well-validated tool that any of you can use in your clinic,” he said.
The American Association for the Study of Liver Disease/Infectious Diseases Society of America hepatitis C guidelines state that the nonproprietary biomarker assays are equivalent to transient elastography for staging fibrosis. Those guidelines are an “outstanding” and extremely user-friendly resource for primary care physicians interested in taking on the treatment of chronic HCV, Dr. Kriss added.
In selecting a DAA, another key resource is the HEP Drug Interactions website, which enables physicians to identify potentially problematic drug-drug interactions. The two most important interactions involve statins or proton pump inhibitors.
Recent studies have shown that the benefits of achieving a sustained virologic response include a clinically meaningful regression of advanced fibrosis at 1 year after treatment in roughly half of patients (Dig Dis Sci. 2018 Feb;63[2]:486-92) and a reduced risk of developing hepatocellular carcinoma (Hepatology. 2018 Jun;67[6]:2244-53).
Models of remote consultation pathways to link primary care providers with consultant HCV specialists are being developed. In a study of 600 patients at federally qualified community health centers in Washington, the risk-adjusted cure rate was 90.4% among patients assigned to a nurse practitioner, 87.6% if DAA therapy was prescribed by a primary care physician, and 84.8% if treated by a specialist. Treatment visit adherence followed the same pattern and correlated with cure rates (Ann Intern Med. 2017 Sep 5;167[5]:311-8).
“Patients might be better off seeing someone they know instead of somebody like me who they’re only going to see one time,” Dr. Kriss observed.
Turning to a couple of controversial expansions of DAA into new populations, Dr. Kriss noted that the AASLD/IDSA guidelines state that active intravenous drug use should not be considered a contraindication to HCV therapy.
“Scaling up HCV treatment in persons who inject drugs is necessary to positively impact the HCV epidemic in the U.S. and globally,” according to the guidelines.
This message was recently underscored by the positive results of the seven-country SIMPLIFY trial, in which 12 weeks of velpatasvir-sofosbuvir (Epclusa) in a population of recent IV drug users achieved a 97% cure rate, with only one reinfection in this high-risk population (Lancet Gastroenterol Hepatol. 2018 Mar;3[3]:153-61).
The hottest controversy in hepatology has been whether to place HCV-positive donor organs in HCV-negative recipients.
“This is intentionally giving hepatitis C to the recipient knowing that he can be cured. Because treatment cure rates are so high, I predict this will become the standard of care in the next year or two,” Dr. Kriss said.
He reported having no financial conflicts regarding his presentation.
.
REPORTING FROM COLORADO IM