Jim Kling

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

Treatment of pediatric obsessive-compulsive disorder (OCD) has evolved in recent years, with more attention given to some of the neuropsychiatric underpinnings of the condition and how they can affect treatment response.

At the Focus on Neuropsychiatry 2021 meeting, Jeffrey Strawn, MD, outlined some of the neuropsychiatry affecting disease and potential mechanisms to help control obsessions and behaviors, and how they may fit with some therapeutic regimens.

Dr. Strawn discussed the psychological construct of cognitive control, which can provide patients an “out” from the cycle of obsession/fear/worry and compulsion/avoidance. In the face of distress, compulsion and avoidance lead to relief, which reinforces the obsession/fear/worry; this in turn leads to more distress.

“We have an escape door for this circuit” in the form of cognitive control, said Dr. Strawn, who is an associate professor of pediatrics at Cincinnati Children’s Hospital Medical Center.

Cognitive control is linked to insight, which can in turn increase adaptive behaviors that help the patient resist the compulsion. Patients won’t eliminate distress, but they can be helped to make it more tolerable. Therapists can then help them move toward goal-directed thoughts and behaviors. Cognitive control is associated with several neural networks, but Dr. Strawn focused on two: the frontoparietal network, associated with top-down regulation; and the cingular-opercular network. Both of these are engaged during cognitive control processes, and play a role inhibitory control and error monitoring.

Dr. Strawn discussed a recent study that explored the neurofunctional basis of treatment. It compared the effects of a stress management therapy and cognitive-behavioral therapy (CBT) in children and adults with OCD at 6 and 12 weeks. The study found similar symptom reductions in both adults and adolescents in both intervention groups.

Before initiating treatment, the researchers conducted functional MRI scans of participants while conducting an incentive flanker task, which reveals brain activity in response to cognitive control and reward processing.

A larger therapeutic response was found in the CBT group among patients who had a larger pretreatment activation within the right temporal lobe and rostral anterior cingulate cortex during cognitive control, as well as those with more activation within the medial prefrontal, orbitofrontal, lateral prefrontal, and amygdala regions during reward processing. On the other hand, within the stress management therapy group, treatment responses were better among those who had lower pretreatment activation among overlapping regions.

“There was a difference in terms of the neurofunctional predictors of treatment response. One of the key regions is the medial prefrontal cortex as well as the rostral anterior cingulate,” said Dr. Strawn, at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

On the neuropharmacology side, numerous medications have been approved for OCD. Dr. Strawn highlighted some studies to illustrate general OCD treatment concepts. That included the 2004 Pediatric OCD Treatment Study, which was one of the only trials to compare placebo with an SSRI, CBT, and the combination of SSRI and CBT. It showed the best results with combination therapy, and the difference appeared early in the treatment course.

That study had aggressive dosing, which led to some issues with sertraline tolerability. Dr. Strawn showed results of a study at his institution which showed that the drug levels of pediatric patients treated with sertraline depended on CYP2C19 metabolism, which affects overall exposure and peak dose concentration. In pediatric populations, some SSRIs clear more slowly and can have high peak concentrations. SSRIs have more side effects than serotonin and norepinephrine reuptake inhibitors in both anxiety disorders and OCD. A key difference between the two is that SSRI treatment is associated with greater frequency of activation, which is difficult to define, but includes restlessness and agitation and insomnia in the beginning stages of treatment.

SSRIs also lead to improvement early in the course of treatment, which was shown in a meta-analysis of nine trials. However, the same study showed that clomipramine is associated with a faster and greater magnitude of improvement, compared with SSRIs, even when the latter are dosed aggressively.

Clomipramine is a potent inhibitor of both serotonin and norepinephrine reuptake. It is recommended to monitor clomipramine levels in pediatric OCD patients, and Dr. Strawn suggested that monitoring should include both the parent drug and its primary metabolite, norclomipramine. At a given dose, there can be a great deal of variation in drug level. The clomipramine/norclomipramine ratio can provide information about the patient’s metabolic state, as well as drug adherence.

Dr. Strawn noted that peak levels occur around 1-3 hours after the dose, “and we really do want at least a 12-hour trough level.” EKGs should be performed at baseline and after any titration of clomipramine dose.

He also discussed pediatric OCD patients with OCD and tics. About one-third of Tourette syndrome patients experience OCD at some point. Tics often improve, whereas OCD more often persists. Tics that co-occur with OCD are associated with a lesser response to SSRI treatment, but not CBT treatment. Similarly, patients with hoarding tendencies are about one-third less likely to respond to SSRIs, CBT, or combination therapy.

Dr. Strawn discussed the concept of accommodation, in which family members cope with a patient’s behavior by altering routines to minimize distress and impairment. This may take the form of facilitating rituals, providing reassurance about a patient’s fears, acquiescing to demands, reducing the child’s day-to-day responsibilities, or helping the child complete tasks. Such actions are well intentioned, but they undermine cognitive control, negatively reinforce symptom engagement, and are associated with functional impairment. Reassurance is the most important behavior, occurring in more than half of patients, and it’s measurable. Parental involvement with rituals is also a concern. “This is associated with higher levels of child OCD severity, as well as parental psychopathology, and lower family cohesion. So oftentimes, there’s a real need to incorporate a family component for the therapeutic aspect of OCD treatment in children and adolescents,” said Dr. Strawn.

New developments in neurobiology and neuropsychology have changed the view of exposure. The old model emphasized the child’s fear rating as an index of corrective learning. The idea was that habituation would decrease anxiety and distress from future exposures. The new model revolves around inhibitory learning theory, which focuses on the variability of distress and aims to increase tolerance of distress. Another goal is to develop new, non-threat associations.

Finally, Dr. Strawn pointed out predictors of poor outcomes in pediatric OCD, including factors such as compulsion severity, oppositional behavior, frequent handwashing, functional impairment, lack of insight, externalizing symptoms, and possibly hoarding. Problematic family characteristics include higher levels of accommodation, parental anxiety, low family cohesion, and high levels of conflict. “The last three really represent a very concerning triad of family behaviors that may necessitate specific family work in order to facilitate the recovery of the pediatric patient,” Dr. Strawn said.

During the question-and-answer session after the talk, Dr. Strawn was asked whether there might be an inflammatory component to OCD, and whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) might be a prodromal condition. He noted that some studies have shown a relationship, but results have been mixed, with lots of heterogeneity within the studied populations. To be suspicious that a patient had OCD resulting from PANDAS would require a high threshold, including an acute onset of symptoms. “This is a situation also where I would tend to involve consultation with some other specialties, including neurology. And obviously there would be follow-up in terms of the general workup,” he said.

Dr. Strawn has received research funding from Allergan, Otsuka, and Myriad Genetics. He has consulted for Myriad Genetics, and is a speaker for CMEology and the Neuroscience Education Institute.

Treatment of pediatric obsessive-compulsive disorder (OCD) has evolved in recent years, with more attention given to some of the neuropsychiatric underpinnings of the condition and how they can affect treatment response.

At the Focus on Neuropsychiatry 2021 meeting, Jeffrey Strawn, MD, outlined some of the neuropsychiatry affecting disease and potential mechanisms to help control obsessions and behaviors, and how they may fit with some therapeutic regimens.

Dr. Strawn discussed the psychological construct of cognitive control, which can provide patients an “out” from the cycle of obsession/fear/worry and compulsion/avoidance. In the face of distress, compulsion and avoidance lead to relief, which reinforces the obsession/fear/worry; this in turn leads to more distress.

“We have an escape door for this circuit” in the form of cognitive control, said Dr. Strawn, who is an associate professor of pediatrics at Cincinnati Children’s Hospital Medical Center.

Cognitive control is linked to insight, which can in turn increase adaptive behaviors that help the patient resist the compulsion. Patients won’t eliminate distress, but they can be helped to make it more tolerable. Therapists can then help them move toward goal-directed thoughts and behaviors. Cognitive control is associated with several neural networks, but Dr. Strawn focused on two: the frontoparietal network, associated with top-down regulation; and the cingular-opercular network. Both of these are engaged during cognitive control processes, and play a role inhibitory control and error monitoring.

Dr. Strawn discussed a recent study that explored the neurofunctional basis of treatment. It compared the effects of a stress management therapy and cognitive-behavioral therapy (CBT) in children and adults with OCD at 6 and 12 weeks. The study found similar symptom reductions in both adults and adolescents in both intervention groups.

Before initiating treatment, the researchers conducted functional MRI scans of participants while conducting an incentive flanker task, which reveals brain activity in response to cognitive control and reward processing.

A larger therapeutic response was found in the CBT group among patients who had a larger pretreatment activation within the right temporal lobe and rostral anterior cingulate cortex during cognitive control, as well as those with more activation within the medial prefrontal, orbitofrontal, lateral prefrontal, and amygdala regions during reward processing. On the other hand, within the stress management therapy group, treatment responses were better among those who had lower pretreatment activation among overlapping regions.

“There was a difference in terms of the neurofunctional predictors of treatment response. One of the key regions is the medial prefrontal cortex as well as the rostral anterior cingulate,” said Dr. Strawn, at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

On the neuropharmacology side, numerous medications have been approved for OCD. Dr. Strawn highlighted some studies to illustrate general OCD treatment concepts. That included the 2004 Pediatric OCD Treatment Study, which was one of the only trials to compare placebo with an SSRI, CBT, and the combination of SSRI and CBT. It showed the best results with combination therapy, and the difference appeared early in the treatment course.

That study had aggressive dosing, which led to some issues with sertraline tolerability. Dr. Strawn showed results of a study at his institution which showed that the drug levels of pediatric patients treated with sertraline depended on CYP2C19 metabolism, which affects overall exposure and peak dose concentration. In pediatric populations, some SSRIs clear more slowly and can have high peak concentrations. SSRIs have more side effects than serotonin and norepinephrine reuptake inhibitors in both anxiety disorders and OCD. A key difference between the two is that SSRI treatment is associated with greater frequency of activation, which is difficult to define, but includes restlessness and agitation and insomnia in the beginning stages of treatment.

SSRIs also lead to improvement early in the course of treatment, which was shown in a meta-analysis of nine trials. However, the same study showed that clomipramine is associated with a faster and greater magnitude of improvement, compared with SSRIs, even when the latter are dosed aggressively.

Clomipramine is a potent inhibitor of both serotonin and norepinephrine reuptake. It is recommended to monitor clomipramine levels in pediatric OCD patients, and Dr. Strawn suggested that monitoring should include both the parent drug and its primary metabolite, norclomipramine. At a given dose, there can be a great deal of variation in drug level. The clomipramine/norclomipramine ratio can provide information about the patient’s metabolic state, as well as drug adherence.

Dr. Strawn noted that peak levels occur around 1-3 hours after the dose, “and we really do want at least a 12-hour trough level.” EKGs should be performed at baseline and after any titration of clomipramine dose.

He also discussed pediatric OCD patients with OCD and tics. About one-third of Tourette syndrome patients experience OCD at some point. Tics often improve, whereas OCD more often persists. Tics that co-occur with OCD are associated with a lesser response to SSRI treatment, but not CBT treatment. Similarly, patients with hoarding tendencies are about one-third less likely to respond to SSRIs, CBT, or combination therapy.

Dr. Strawn discussed the concept of accommodation, in which family members cope with a patient’s behavior by altering routines to minimize distress and impairment. This may take the form of facilitating rituals, providing reassurance about a patient’s fears, acquiescing to demands, reducing the child’s day-to-day responsibilities, or helping the child complete tasks. Such actions are well intentioned, but they undermine cognitive control, negatively reinforce symptom engagement, and are associated with functional impairment. Reassurance is the most important behavior, occurring in more than half of patients, and it’s measurable. Parental involvement with rituals is also a concern. “This is associated with higher levels of child OCD severity, as well as parental psychopathology, and lower family cohesion. So oftentimes, there’s a real need to incorporate a family component for the therapeutic aspect of OCD treatment in children and adolescents,” said Dr. Strawn.

New developments in neurobiology and neuropsychology have changed the view of exposure. The old model emphasized the child’s fear rating as an index of corrective learning. The idea was that habituation would decrease anxiety and distress from future exposures. The new model revolves around inhibitory learning theory, which focuses on the variability of distress and aims to increase tolerance of distress. Another goal is to develop new, non-threat associations.

Finally, Dr. Strawn pointed out predictors of poor outcomes in pediatric OCD, including factors such as compulsion severity, oppositional behavior, frequent handwashing, functional impairment, lack of insight, externalizing symptoms, and possibly hoarding. Problematic family characteristics include higher levels of accommodation, parental anxiety, low family cohesion, and high levels of conflict. “The last three really represent a very concerning triad of family behaviors that may necessitate specific family work in order to facilitate the recovery of the pediatric patient,” Dr. Strawn said.

During the question-and-answer session after the talk, Dr. Strawn was asked whether there might be an inflammatory component to OCD, and whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) might be a prodromal condition. He noted that some studies have shown a relationship, but results have been mixed, with lots of heterogeneity within the studied populations. To be suspicious that a patient had OCD resulting from PANDAS would require a high threshold, including an acute onset of symptoms. “This is a situation also where I would tend to involve consultation with some other specialties, including neurology. And obviously there would be follow-up in terms of the general workup,” he said.

Dr. Strawn has received research funding from Allergan, Otsuka, and Myriad Genetics. He has consulted for Myriad Genetics, and is a speaker for CMEology and the Neuroscience Education Institute.

Treatment of pediatric obsessive-compulsive disorder (OCD) has evolved in recent years, with more attention given to some of the neuropsychiatric underpinnings of the condition and how they can affect treatment response.

At the Focus on Neuropsychiatry 2021 meeting, Jeffrey Strawn, MD, outlined some of the neuropsychiatry affecting disease and potential mechanisms to help control obsessions and behaviors, and how they may fit with some therapeutic regimens.

Dr. Strawn discussed the psychological construct of cognitive control, which can provide patients an “out” from the cycle of obsession/fear/worry and compulsion/avoidance. In the face of distress, compulsion and avoidance lead to relief, which reinforces the obsession/fear/worry; this in turn leads to more distress.

“We have an escape door for this circuit” in the form of cognitive control, said Dr. Strawn, who is an associate professor of pediatrics at Cincinnati Children’s Hospital Medical Center.

Cognitive control is linked to insight, which can in turn increase adaptive behaviors that help the patient resist the compulsion. Patients won’t eliminate distress, but they can be helped to make it more tolerable. Therapists can then help them move toward goal-directed thoughts and behaviors. Cognitive control is associated with several neural networks, but Dr. Strawn focused on two: the frontoparietal network, associated with top-down regulation; and the cingular-opercular network. Both of these are engaged during cognitive control processes, and play a role inhibitory control and error monitoring.

Dr. Strawn discussed a recent study that explored the neurofunctional basis of treatment. It compared the effects of a stress management therapy and cognitive-behavioral therapy (CBT) in children and adults with OCD at 6 and 12 weeks. The study found similar symptom reductions in both adults and adolescents in both intervention groups.

Before initiating treatment, the researchers conducted functional MRI scans of participants while conducting an incentive flanker task, which reveals brain activity in response to cognitive control and reward processing.

A larger therapeutic response was found in the CBT group among patients who had a larger pretreatment activation within the right temporal lobe and rostral anterior cingulate cortex during cognitive control, as well as those with more activation within the medial prefrontal, orbitofrontal, lateral prefrontal, and amygdala regions during reward processing. On the other hand, within the stress management therapy group, treatment responses were better among those who had lower pretreatment activation among overlapping regions.

“There was a difference in terms of the neurofunctional predictors of treatment response. One of the key regions is the medial prefrontal cortex as well as the rostral anterior cingulate,” said Dr. Strawn, at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

On the neuropharmacology side, numerous medications have been approved for OCD. Dr. Strawn highlighted some studies to illustrate general OCD treatment concepts. That included the 2004 Pediatric OCD Treatment Study, which was one of the only trials to compare placebo with an SSRI, CBT, and the combination of SSRI and CBT. It showed the best results with combination therapy, and the difference appeared early in the treatment course.

That study had aggressive dosing, which led to some issues with sertraline tolerability. Dr. Strawn showed results of a study at his institution which showed that the drug levels of pediatric patients treated with sertraline depended on CYP2C19 metabolism, which affects overall exposure and peak dose concentration. In pediatric populations, some SSRIs clear more slowly and can have high peak concentrations. SSRIs have more side effects than serotonin and norepinephrine reuptake inhibitors in both anxiety disorders and OCD. A key difference between the two is that SSRI treatment is associated with greater frequency of activation, which is difficult to define, but includes restlessness and agitation and insomnia in the beginning stages of treatment.

SSRIs also lead to improvement early in the course of treatment, which was shown in a meta-analysis of nine trials. However, the same study showed that clomipramine is associated with a faster and greater magnitude of improvement, compared with SSRIs, even when the latter are dosed aggressively.

Clomipramine is a potent inhibitor of both serotonin and norepinephrine reuptake. It is recommended to monitor clomipramine levels in pediatric OCD patients, and Dr. Strawn suggested that monitoring should include both the parent drug and its primary metabolite, norclomipramine. At a given dose, there can be a great deal of variation in drug level. The clomipramine/norclomipramine ratio can provide information about the patient’s metabolic state, as well as drug adherence.

Dr. Strawn noted that peak levels occur around 1-3 hours after the dose, “and we really do want at least a 12-hour trough level.” EKGs should be performed at baseline and after any titration of clomipramine dose.

He also discussed pediatric OCD patients with OCD and tics. About one-third of Tourette syndrome patients experience OCD at some point. Tics often improve, whereas OCD more often persists. Tics that co-occur with OCD are associated with a lesser response to SSRI treatment, but not CBT treatment. Similarly, patients with hoarding tendencies are about one-third less likely to respond to SSRIs, CBT, or combination therapy.

Dr. Strawn discussed the concept of accommodation, in which family members cope with a patient’s behavior by altering routines to minimize distress and impairment. This may take the form of facilitating rituals, providing reassurance about a patient’s fears, acquiescing to demands, reducing the child’s day-to-day responsibilities, or helping the child complete tasks. Such actions are well intentioned, but they undermine cognitive control, negatively reinforce symptom engagement, and are associated with functional impairment. Reassurance is the most important behavior, occurring in more than half of patients, and it’s measurable. Parental involvement with rituals is also a concern. “This is associated with higher levels of child OCD severity, as well as parental psychopathology, and lower family cohesion. So oftentimes, there’s a real need to incorporate a family component for the therapeutic aspect of OCD treatment in children and adolescents,” said Dr. Strawn.

New developments in neurobiology and neuropsychology have changed the view of exposure. The old model emphasized the child’s fear rating as an index of corrective learning. The idea was that habituation would decrease anxiety and distress from future exposures. The new model revolves around inhibitory learning theory, which focuses on the variability of distress and aims to increase tolerance of distress. Another goal is to develop new, non-threat associations.

Finally, Dr. Strawn pointed out predictors of poor outcomes in pediatric OCD, including factors such as compulsion severity, oppositional behavior, frequent handwashing, functional impairment, lack of insight, externalizing symptoms, and possibly hoarding. Problematic family characteristics include higher levels of accommodation, parental anxiety, low family cohesion, and high levels of conflict. “The last three really represent a very concerning triad of family behaviors that may necessitate specific family work in order to facilitate the recovery of the pediatric patient,” Dr. Strawn said.

During the question-and-answer session after the talk, Dr. Strawn was asked whether there might be an inflammatory component to OCD, and whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) might be a prodromal condition. He noted that some studies have shown a relationship, but results have been mixed, with lots of heterogeneity within the studied populations. To be suspicious that a patient had OCD resulting from PANDAS would require a high threshold, including an acute onset of symptoms. “This is a situation also where I would tend to involve consultation with some other specialties, including neurology. And obviously there would be follow-up in terms of the general workup,” he said.

Dr. Strawn has received research funding from Allergan, Otsuka, and Myriad Genetics. He has consulted for Myriad Genetics, and is a speaker for CMEology and the Neuroscience Education Institute.

Schizophrenia is a complex disease caused by dysfunction in specific brain regions or circuits. In fact, schizophrenia is not a single disease but several hundred different diseases, according to Henry A. Nasrallah, MD, who spoke on the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The underlying causes of schizophrenia can be either genetic or environmental, but all involve changes in brain development in the fetus or newborn. Psychosis can occur in a range of disorders, including epilepsy, Parkinson’s disease, cerebral tumors, and narcolepsy, to name just a few. Although it starts out as a neurodevelopmental disorder, schizophrenia becomes neurodegenerative after onset, with each new psychotic episode leading to further damage, said Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati. Further damage leaves patients with greater and greater disability over time, said Dr. Nasrallah at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

The course of illness in some ways resembles the cascading disability associated with strokes. Schizophrenia relapses lead to subcortical atrophy, ventricular enlargement, and further loss of white matter. The accumulating damage is a result of microglia activation, which leads to neuroinflammation and oxidative stress. Mitochondria may also produce insufficient amounts of the antioxidant glutathione.

This pattern in schizophrenia makes it all the more important to ensure that patients stay on medication to prevent future episodes. “The main reason for relapse in schizophrenia is poor adherence to antipsychotic medications, due to anosognosia, memory impairment, avolition, and substance use. It is absolutely necessary to realize that, while oral antipsychotics are effective in the hospital due to enforced compliance by the nursing staff, patients should be switched to long-acting injectable antipsychotics (LAIs) upon discharge from the first episode, which astonishingly is rarely done by 99% of clinicians,” said Dr. Nasrallah in an interview.

That frequent failure leads to further neurodegeneration and increasing disability, which in turn can lead to high rates of homelessness, suicide, and as well as incarceration, because many state hospitals that used to provide medical care for relapsing individuals have been closed down. All of these consequences place great financial and emotional burdens on families and loved ones.
 

Reconceptualizing the illness

Dr. Nasrallah also advocated that schizophrenia should be classified as a neurologic disorder instead of a psychiatric disorder. He said that the neuropsychiatric mechanisms behind these related diseases support that classification, and neurologic disorders receive much more insurance coverage.

The neuroinflammatory mechanisms underlying schizophrenia suggest that therapies such as omega-3 fatty acids could provide benefit during the prodromal stages of illness. Antioxidants like N-acetyl cysteine could potentially be useful during psychotic episodes, since it boosts levels of glutathione to reduce damaging free radicals. Other approaches could prevent microglia activation, which appears to initiate neurodegeneration.

Another consequence of psychosis is programmed cell death, or apoptosis, in response to reduced levels of neurotropic agents. That could potentially be countered using agents to prevent apoptosis.

Dr. Nasrallah believes clinicians should not use first-generation antipsychotics such as haloperidol, because research has shown that those drugs, while effective, also destroy neurons. Second-generation antipsychotics (SGAs) are safer and avoid that neurotoxicity, and they also have a neuroprotective effect. The SGAs may owe their improved efficacy and safety to the fact that they don’t bind as strongly to dopamine receptors, and they are stronger 5-hydroxytryptamine_2A antagonists, according to Dr. Nasrallah. A meta-analysis of 18 studies showed that patients on SGAs maintained gray matter volume, and may even achieve increases in the hippocampus and the prefrontal cortex.

In the Q&A session after the presentation, Dr. Nasrallah was asked whether treatment should be kept up for the rest of the patient’s life, or whether medication should be tapered – and perhaps stopped. He likened treatment of schizophrenia to diabetes or high blood pressure.

“It’s an illness. A lot of medical disorders require lifetime treatment, and there is no difference between psychiatry and the rest of medicine,” he said. “You have to continue the medication at the dose that worked in the acute episode, hopefully the lowest possible dose.”

Dr. Nasrallah did concede that it can be challenging to get patients to accept permanent treatment, and he shared his own strategy to achieve that outcome. “I don’t tell the patient, ‘You’re going to take this the rest of your life.’ It depresses them. So I say, ‘Let’s keep this on board for a year, and I’ll see you regularly, and I’ll monitor you, and we’ll see how it goes, and then we will make another decision at the end of the year.’ ”

During that year, Dr. Nasrallah educates the patient and develops a rapport. “I will show them a lot of data and information about the illness and the hazards of stopping [treatment]. And by the end of the year, most of my patients say: ‘Yeah, I agree. Let’s continue the good thing and let’s not fix something that’s not broken.’ ”

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has also served on a speaker’s bureau for most of those companies, in addition to that of Noven.

Schizophrenia is a complex disease caused by dysfunction in specific brain regions or circuits. In fact, schizophrenia is not a single disease but several hundred different diseases, according to Henry A. Nasrallah, MD, who spoke on the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The underlying causes of schizophrenia can be either genetic or environmental, but all involve changes in brain development in the fetus or newborn. Psychosis can occur in a range of disorders, including epilepsy, Parkinson’s disease, cerebral tumors, and narcolepsy, to name just a few. Although it starts out as a neurodevelopmental disorder, schizophrenia becomes neurodegenerative after onset, with each new psychotic episode leading to further damage, said Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati. Further damage leaves patients with greater and greater disability over time, said Dr. Nasrallah at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

The course of illness in some ways resembles the cascading disability associated with strokes. Schizophrenia relapses lead to subcortical atrophy, ventricular enlargement, and further loss of white matter. The accumulating damage is a result of microglia activation, which leads to neuroinflammation and oxidative stress. Mitochondria may also produce insufficient amounts of the antioxidant glutathione.

This pattern in schizophrenia makes it all the more important to ensure that patients stay on medication to prevent future episodes. “The main reason for relapse in schizophrenia is poor adherence to antipsychotic medications, due to anosognosia, memory impairment, avolition, and substance use. It is absolutely necessary to realize that, while oral antipsychotics are effective in the hospital due to enforced compliance by the nursing staff, patients should be switched to long-acting injectable antipsychotics (LAIs) upon discharge from the first episode, which astonishingly is rarely done by 99% of clinicians,” said Dr. Nasrallah in an interview.

That frequent failure leads to further neurodegeneration and increasing disability, which in turn can lead to high rates of homelessness, suicide, and as well as incarceration, because many state hospitals that used to provide medical care for relapsing individuals have been closed down. All of these consequences place great financial and emotional burdens on families and loved ones.
 

Reconceptualizing the illness

Dr. Nasrallah also advocated that schizophrenia should be classified as a neurologic disorder instead of a psychiatric disorder. He said that the neuropsychiatric mechanisms behind these related diseases support that classification, and neurologic disorders receive much more insurance coverage.

The neuroinflammatory mechanisms underlying schizophrenia suggest that therapies such as omega-3 fatty acids could provide benefit during the prodromal stages of illness. Antioxidants like N-acetyl cysteine could potentially be useful during psychotic episodes, since it boosts levels of glutathione to reduce damaging free radicals. Other approaches could prevent microglia activation, which appears to initiate neurodegeneration.

Another consequence of psychosis is programmed cell death, or apoptosis, in response to reduced levels of neurotropic agents. That could potentially be countered using agents to prevent apoptosis.

Dr. Nasrallah believes clinicians should not use first-generation antipsychotics such as haloperidol, because research has shown that those drugs, while effective, also destroy neurons. Second-generation antipsychotics (SGAs) are safer and avoid that neurotoxicity, and they also have a neuroprotective effect. The SGAs may owe their improved efficacy and safety to the fact that they don’t bind as strongly to dopamine receptors, and they are stronger 5-hydroxytryptamine_2A antagonists, according to Dr. Nasrallah. A meta-analysis of 18 studies showed that patients on SGAs maintained gray matter volume, and may even achieve increases in the hippocampus and the prefrontal cortex.

In the Q&A session after the presentation, Dr. Nasrallah was asked whether treatment should be kept up for the rest of the patient’s life, or whether medication should be tapered – and perhaps stopped. He likened treatment of schizophrenia to diabetes or high blood pressure.

“It’s an illness. A lot of medical disorders require lifetime treatment, and there is no difference between psychiatry and the rest of medicine,” he said. “You have to continue the medication at the dose that worked in the acute episode, hopefully the lowest possible dose.”

Dr. Nasrallah did concede that it can be challenging to get patients to accept permanent treatment, and he shared his own strategy to achieve that outcome. “I don’t tell the patient, ‘You’re going to take this the rest of your life.’ It depresses them. So I say, ‘Let’s keep this on board for a year, and I’ll see you regularly, and I’ll monitor you, and we’ll see how it goes, and then we will make another decision at the end of the year.’ ”

During that year, Dr. Nasrallah educates the patient and develops a rapport. “I will show them a lot of data and information about the illness and the hazards of stopping [treatment]. And by the end of the year, most of my patients say: ‘Yeah, I agree. Let’s continue the good thing and let’s not fix something that’s not broken.’ ”

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has also served on a speaker’s bureau for most of those companies, in addition to that of Noven.

Schizophrenia is a complex disease caused by dysfunction in specific brain regions or circuits. In fact, schizophrenia is not a single disease but several hundred different diseases, according to Henry A. Nasrallah, MD, who spoke on the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The underlying causes of schizophrenia can be either genetic or environmental, but all involve changes in brain development in the fetus or newborn. Psychosis can occur in a range of disorders, including epilepsy, Parkinson’s disease, cerebral tumors, and narcolepsy, to name just a few. Although it starts out as a neurodevelopmental disorder, schizophrenia becomes neurodegenerative after onset, with each new psychotic episode leading to further damage, said Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati. Further damage leaves patients with greater and greater disability over time, said Dr. Nasrallah at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

The course of illness in some ways resembles the cascading disability associated with strokes. Schizophrenia relapses lead to subcortical atrophy, ventricular enlargement, and further loss of white matter. The accumulating damage is a result of microglia activation, which leads to neuroinflammation and oxidative stress. Mitochondria may also produce insufficient amounts of the antioxidant glutathione.

This pattern in schizophrenia makes it all the more important to ensure that patients stay on medication to prevent future episodes. “The main reason for relapse in schizophrenia is poor adherence to antipsychotic medications, due to anosognosia, memory impairment, avolition, and substance use. It is absolutely necessary to realize that, while oral antipsychotics are effective in the hospital due to enforced compliance by the nursing staff, patients should be switched to long-acting injectable antipsychotics (LAIs) upon discharge from the first episode, which astonishingly is rarely done by 99% of clinicians,” said Dr. Nasrallah in an interview.

That frequent failure leads to further neurodegeneration and increasing disability, which in turn can lead to high rates of homelessness, suicide, and as well as incarceration, because many state hospitals that used to provide medical care for relapsing individuals have been closed down. All of these consequences place great financial and emotional burdens on families and loved ones.
 

Reconceptualizing the illness

Dr. Nasrallah also advocated that schizophrenia should be classified as a neurologic disorder instead of a psychiatric disorder. He said that the neuropsychiatric mechanisms behind these related diseases support that classification, and neurologic disorders receive much more insurance coverage.

The neuroinflammatory mechanisms underlying schizophrenia suggest that therapies such as omega-3 fatty acids could provide benefit during the prodromal stages of illness. Antioxidants like N-acetyl cysteine could potentially be useful during psychotic episodes, since it boosts levels of glutathione to reduce damaging free radicals. Other approaches could prevent microglia activation, which appears to initiate neurodegeneration.

Another consequence of psychosis is programmed cell death, or apoptosis, in response to reduced levels of neurotropic agents. That could potentially be countered using agents to prevent apoptosis.

Dr. Nasrallah believes clinicians should not use first-generation antipsychotics such as haloperidol, because research has shown that those drugs, while effective, also destroy neurons. Second-generation antipsychotics (SGAs) are safer and avoid that neurotoxicity, and they also have a neuroprotective effect. The SGAs may owe their improved efficacy and safety to the fact that they don’t bind as strongly to dopamine receptors, and they are stronger 5-hydroxytryptamine_2A antagonists, according to Dr. Nasrallah. A meta-analysis of 18 studies showed that patients on SGAs maintained gray matter volume, and may even achieve increases in the hippocampus and the prefrontal cortex.

In the Q&A session after the presentation, Dr. Nasrallah was asked whether treatment should be kept up for the rest of the patient’s life, or whether medication should be tapered – and perhaps stopped. He likened treatment of schizophrenia to diabetes or high blood pressure.

“It’s an illness. A lot of medical disorders require lifetime treatment, and there is no difference between psychiatry and the rest of medicine,” he said. “You have to continue the medication at the dose that worked in the acute episode, hopefully the lowest possible dose.”

Dr. Nasrallah did concede that it can be challenging to get patients to accept permanent treatment, and he shared his own strategy to achieve that outcome. “I don’t tell the patient, ‘You’re going to take this the rest of your life.’ It depresses them. So I say, ‘Let’s keep this on board for a year, and I’ll see you regularly, and I’ll monitor you, and we’ll see how it goes, and then we will make another decision at the end of the year.’ ”

During that year, Dr. Nasrallah educates the patient and develops a rapport. “I will show them a lot of data and information about the illness and the hazards of stopping [treatment]. And by the end of the year, most of my patients say: ‘Yeah, I agree. Let’s continue the good thing and let’s not fix something that’s not broken.’ ”

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has also served on a speaker’s bureau for most of those companies, in addition to that of Noven.

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.

Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.

IED is also more common than people generally suspect, with an estimated 4% lifetime incidence, according to Dr. Coccaro, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.

The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.

Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.

“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.

The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”

Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.

Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.

Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.

Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.

Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”

During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.

“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.

For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.

Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
 

Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.

Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.

IED is also more common than people generally suspect, with an estimated 4% lifetime incidence, according to Dr. Coccaro, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.

The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.

Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.

“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.

The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”

Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.

Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.

Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.

Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.

Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”

During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.

“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.

For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.

Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
 

Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.

Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.

IED is also more common than people generally suspect, with an estimated 4% lifetime incidence, according to Dr. Coccaro, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.

The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.

Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.

“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.

The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”

Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.

Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.

Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.

Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.

Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”

During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.

“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.

For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.

Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
 

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

Adding or switching biologics is a common practice in the treatment of patients with inflammatory bowel disease (IBD), but there is a dearth of clinical data on whether patients should receive their first or second biologic as monotherapy or combined with immunomodulatory therapies. It’s a clinical conundrum made more difficult by the increasing number of biologics and drugs available to treat IBD, and the fact that some first-line biologics may fail because of immune responses.

The authors of a new review by Roni Aoun, MD, published in the Journal of Clinical Gastroenterology sought to provide some much-needed advice on these issues, surveying the literature that does exist in order to offer evidence-based recommendations for how and when biologics should be used.
 

A confusing array of therapeutic choices

The review arrives at a moment when IBD treatments have hit a therapeutic plateau, producing remission rates of only around 30%-35%, despite new treatments and mechanisms of action. “That’s just not where we want to be [so] there’s a lot of interest in how we can make our therapies better,” said David Rubin, MD, a professor of medicine and the codirector of the Digestive Diseases Center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation.

Dr. Rubin, who did not participate in authoring the review, added that the field also faces questions of what patients should receive after their first has either failed to work entirely or the initial response has waned.

“Understanding sequencing is important,” he said. “The best way to assess that right now has been through claims data, which are notoriously missing important information like [disease activity].”

The landmark SONIC and SUCCESS studies concluded that combining antibodies with immunomodulatory drugs was the best approach, but times have changed since these results were published. One recent study showed that the patient’s HLA subtype can be associated with anti–tumor necrosis factor (TNF) immune responses.

“We now know that you can be much more specific and precise about this. You can predict the likelihood someone’s going to have antidrug antibodies against an anti-TNF [agent],” said Dr. Rubin.

Factors that go into the decision of whether or not to prescribe an immunomodulator include the class of biologic, whether it is a first or second biologic, the presence or absence of antidrug antibodies, patient preference, and any comorbid conditions.

Anti-TNF agents often lose efficacy, with one study finding an average 41% loss of response to certolizumab, 33% to infliximab, and 30% to adalimumab. Another problem is posed by the intrinsic risk of immunogenicity with biologics, with rates reported to be as high as 65.3% for infliximab and 38% for adalimumab.

Immunogenicity to one anti-TNF agent often predicts immunogenicity to other anti-TNF biologics. Some data suggest that, in patients who produced antibodies to an initial anti-TNF agent, combination therapy can provide benefit with a second anti-TNF biologic. However, there are some scenarios that call for monotherapy, such as when a patient can’t take immunomodulators or when over-suppression could be risky. According to Dr. Aoun and colleagues, limited data and lessons from clinical practice suggest that monotherapy anti-TNF biologics with proactive therapeutic drug monitoring is a reasonable approach in these cases. Monitoring may also reduce the risk of immunogenicity.
 

What the authors recommended

For those reasons, if the first biologic is an anti-TNF agent, the authors recommend an immunomodulator combined with anti-TNF agents for induction or maintenance treatment of either ulcerative colitis or Crohn’s disease. If immunogenicity is present after a loss of response, they recommend a second anti-TNF agent with an immunomodulator. If there is no immunogenicity and the failure is mechanistic, they recommend switching to vedolizumab monotherapy or ustekinumab monotherapy. Immunomodulators can be prescribed on an individualized basis.

When vedolizumab or ustekinumab are the patient’s first biologic, they should be used as monotherapy. Both have very low rates of immunogenicity, and an immunomodulator is unlikely to confer a meaningful benefit, according to the review authors, who nonetheless called for prospective trials to explore these questions further. If there is a loss of response, they recommend anti-TNF agents combined with an immunomodulator, or monotherapy if the second agent is ustekinumab or vedolizumab.

In severe IBD cases, when combining agents with different mechanisms of action, or in patients who have immunogenicity to more than one class of biologic, the authors don’t provide general recommendations. Instead, they noted that the risks and benefits to individual patients should be weighed for combinations with immunomodulators.

The authors declare that they have nothing to disclose. Dr. Rubin has consulted for Janssen, AbbVie, and Takeda.

In a real-life setting, fecal calprotectin (FC) home testing performed well at predicting disease endoscopic activity in patients with inflammatory bowel disease (IBD) being treated with adalimumab.

The study, published in the European Journal of Gastroenterology & Hepatology, could be a boon to patients and physicians employing the treat-to-target (T2T) strategy, which relies on disease monitoring through methods like endoscopy, histology, and serum and fecal biomarkers.

One goal of T2T is to identify patients who are asymptomatic in order to prevent or minimize flare-ups. Colonoscopy is the preferred approach for achieving this, but cost, risk, and patient reluctance limit its use. FC has gained attention in recent years, as it outperforms serum biomarkers in its correlation with clinical, endoscopic, and histological disease activity. Consecutive FC measurements predict disease relapse among asymptomatic patients with high specificity and sensitivity. There’s also evidence that it could be useful for perioperative monitoring.

FC is typically assessed in a lab, but the recent availability of smartphone-based tests has allowed patients to collect and test their stool at home. The method has been tested through clinical research, but real-world data have so far been lacking.
 

First real-life results

In what they described as the first real-life study of its kind, researchers offered at-home FC testing every 4 months to all 72 current IBD patients taking adalimumab at the University Hospital of Heraklion, University of Crete, Irakleio, Greece; seven patients (10%) declined to take part in at-home FC testing. Of the remaining 65, the mean age was 42.3 years, and 58% were male; 89% had a diagnosis of Crohn’s disease. The mean disease duration was 13.3 years.

Abnormal FC values were confirmed with a follow-up test 1 month later, after which point a colonoscopy was scheduled to inform treatment modification. Twenty-four patients (37% of the population) had two positive tests, and 19 who were able underwent colonoscopy. Twelve patients (19%) underwent adalimumab dose intensification, 9 (14%) switched to a different biologic, and 2 (3%) had surgery.

The group of patients who required treatment modification had a significantly higher median FC concentration of 761 mcg/g (37% had values ≥ 1,000 mcg/g), compared with a median concentration of 108 mcg/g for those who did not have their dose modified (P < .0001). With a cutoff of 250 mcg/g, FC correctly identified a need for treatment with an area under the receiver operating characteristic curve (AUC) value of 0.90 (95% confidence interval, 0.80-0.96).

FC was significantly correlated to endoscopic activity (r = 0.543, P < .001), and patients with endoscopic disease had higher median FC concentrations (689 vs. 99 mcg/g; P < .001).

The researchers calculated that a cutoff value of FC levels greater than 413 mcg/g is optimal for predicting endoscopic disease, with a sensitivity of 75%, a specificity of 76%, a positive likelihood ratio of 3.12, and a negative likelihood ratio of 0.33.
 

Diabeteslike home monitoring for IBD?

“Home monitoring of disease activity and drug levels will be a paradigm shift in management of IBD, because it will place in the patient’s hands the opportunity to assess their disease activity and to have a better understanding of what’s going on when they have symptoms or concerns about their disease control,” commented David Rubin, MD, who did not participate in the study.

He noted that patients are often unsure whether a new symptom is the beginning of another episode of IBD or something unrelated.

“One of the biggest challenges of having IBD is just the perception of loss of control of the disease and knowing when things are going to happen,” said Dr. Rubin, a professor of medicine and the codirector of the digestive diseases center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation. “I often explain to people that using a tool like this would be similar to patients with diabetes checking their blood sugar – getting a feel for what’s actually happening closer to the time that it’s happening, rather than waiting for it to progress. I really think that the general idea of home monitoring is going to be a major advance in our field.”

Although the new study proved the technique’s acceptability and efficacy, it isn’t without pitfalls, according to Dr. Rubin. False positives or negatives are a concern, and other factors might influence the results. For example, proton pump inhibitors can increase FC levels. Another concern is that some patients can become obsessed with their FC levels, and may want to test themselves at any sign of illness. They may develop unrealistic expectations about the impact of medications on their FC levels.

“That’s going to open up a whole dialogue with people, so that we all are on the same page about it. But I think that the benefits of having this far outweigh those potential risks,” said Dr. Rubin.

The authors reported no conflicts of interest. Dr. Rubin has consulted for TECHLAB.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

In a real-life setting, fecal calprotectin (FC) home testing performed well at predicting disease endoscopic activity in patients with inflammatory bowel disease (IBD) being treated with adalimumab.

The study, published in the European Journal of Gastroenterology & Hepatology, could be a boon to patients and physicians employing the treat-to-target (T2T) strategy, which relies on disease monitoring through methods like endoscopy, histology, and serum and fecal biomarkers.

One goal of T2T is to identify patients who are asymptomatic in order to prevent or minimize flare-ups. Colonoscopy is the preferred approach for achieving this, but cost, risk, and patient reluctance limit its use. FC has gained attention in recent years, as it outperforms serum biomarkers in its correlation with clinical, endoscopic, and histological disease activity. Consecutive FC measurements predict disease relapse among asymptomatic patients with high specificity and sensitivity. There’s also evidence that it could be useful for perioperative monitoring.

FC is typically assessed in a lab, but the recent availability of smartphone-based tests has allowed patients to collect and test their stool at home. The method has been tested through clinical research, but real-world data have so far been lacking.
 

First real-life results

In what they described as the first real-life study of its kind, researchers offered at-home FC testing every 4 months to all 72 current IBD patients taking adalimumab at the University Hospital of Heraklion, University of Crete, Irakleio, Greece; seven patients (10%) declined to take part in at-home FC testing. Of the remaining 65, the mean age was 42.3 years, and 58% were male; 89% had a diagnosis of Crohn’s disease. The mean disease duration was 13.3 years.

Abnormal FC values were confirmed with a follow-up test 1 month later, after which point a colonoscopy was scheduled to inform treatment modification. Twenty-four patients (37% of the population) had two positive tests, and 19 who were able underwent colonoscopy. Twelve patients (19%) underwent adalimumab dose intensification, 9 (14%) switched to a different biologic, and 2 (3%) had surgery.

The group of patients who required treatment modification had a significantly higher median FC concentration of 761 mcg/g (37% had values ≥ 1,000 mcg/g), compared with a median concentration of 108 mcg/g for those who did not have their dose modified (P < .0001). With a cutoff of 250 mcg/g, FC correctly identified a need for treatment with an area under the receiver operating characteristic curve (AUC) value of 0.90 (95% confidence interval, 0.80-0.96).

FC was significantly correlated to endoscopic activity (r = 0.543, P < .001), and patients with endoscopic disease had higher median FC concentrations (689 vs. 99 mcg/g; P < .001).

The researchers calculated that a cutoff value of FC levels greater than 413 mcg/g is optimal for predicting endoscopic disease, with a sensitivity of 75%, a specificity of 76%, a positive likelihood ratio of 3.12, and a negative likelihood ratio of 0.33.
 

Diabeteslike home monitoring for IBD?

“Home monitoring of disease activity and drug levels will be a paradigm shift in management of IBD, because it will place in the patient’s hands the opportunity to assess their disease activity and to have a better understanding of what’s going on when they have symptoms or concerns about their disease control,” commented David Rubin, MD, who did not participate in the study.

He noted that patients are often unsure whether a new symptom is the beginning of another episode of IBD or something unrelated.

“One of the biggest challenges of having IBD is just the perception of loss of control of the disease and knowing when things are going to happen,” said Dr. Rubin, a professor of medicine and the codirector of the digestive diseases center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation. “I often explain to people that using a tool like this would be similar to patients with diabetes checking their blood sugar – getting a feel for what’s actually happening closer to the time that it’s happening, rather than waiting for it to progress. I really think that the general idea of home monitoring is going to be a major advance in our field.”

Although the new study proved the technique’s acceptability and efficacy, it isn’t without pitfalls, according to Dr. Rubin. False positives or negatives are a concern, and other factors might influence the results. For example, proton pump inhibitors can increase FC levels. Another concern is that some patients can become obsessed with their FC levels, and may want to test themselves at any sign of illness. They may develop unrealistic expectations about the impact of medications on their FC levels.

“That’s going to open up a whole dialogue with people, so that we all are on the same page about it. But I think that the benefits of having this far outweigh those potential risks,” said Dr. Rubin.

The authors reported no conflicts of interest. Dr. Rubin has consulted for TECHLAB.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

In a real-life setting, fecal calprotectin (FC) home testing performed well at predicting disease endoscopic activity in patients with inflammatory bowel disease (IBD) being treated with adalimumab.

The study, published in the European Journal of Gastroenterology & Hepatology, could be a boon to patients and physicians employing the treat-to-target (T2T) strategy, which relies on disease monitoring through methods like endoscopy, histology, and serum and fecal biomarkers.

One goal of T2T is to identify patients who are asymptomatic in order to prevent or minimize flare-ups. Colonoscopy is the preferred approach for achieving this, but cost, risk, and patient reluctance limit its use. FC has gained attention in recent years, as it outperforms serum biomarkers in its correlation with clinical, endoscopic, and histological disease activity. Consecutive FC measurements predict disease relapse among asymptomatic patients with high specificity and sensitivity. There’s also evidence that it could be useful for perioperative monitoring.

FC is typically assessed in a lab, but the recent availability of smartphone-based tests has allowed patients to collect and test their stool at home. The method has been tested through clinical research, but real-world data have so far been lacking.
 

First real-life results

In what they described as the first real-life study of its kind, researchers offered at-home FC testing every 4 months to all 72 current IBD patients taking adalimumab at the University Hospital of Heraklion, University of Crete, Irakleio, Greece; seven patients (10%) declined to take part in at-home FC testing. Of the remaining 65, the mean age was 42.3 years, and 58% were male; 89% had a diagnosis of Crohn’s disease. The mean disease duration was 13.3 years.

Abnormal FC values were confirmed with a follow-up test 1 month later, after which point a colonoscopy was scheduled to inform treatment modification. Twenty-four patients (37% of the population) had two positive tests, and 19 who were able underwent colonoscopy. Twelve patients (19%) underwent adalimumab dose intensification, 9 (14%) switched to a different biologic, and 2 (3%) had surgery.

The group of patients who required treatment modification had a significantly higher median FC concentration of 761 mcg/g (37% had values ≥ 1,000 mcg/g), compared with a median concentration of 108 mcg/g for those who did not have their dose modified (P < .0001). With a cutoff of 250 mcg/g, FC correctly identified a need for treatment with an area under the receiver operating characteristic curve (AUC) value of 0.90 (95% confidence interval, 0.80-0.96).

FC was significantly correlated to endoscopic activity (r = 0.543, P < .001), and patients with endoscopic disease had higher median FC concentrations (689 vs. 99 mcg/g; P < .001).

The researchers calculated that a cutoff value of FC levels greater than 413 mcg/g is optimal for predicting endoscopic disease, with a sensitivity of 75%, a specificity of 76%, a positive likelihood ratio of 3.12, and a negative likelihood ratio of 0.33.
 

Diabeteslike home monitoring for IBD?

“Home monitoring of disease activity and drug levels will be a paradigm shift in management of IBD, because it will place in the patient’s hands the opportunity to assess their disease activity and to have a better understanding of what’s going on when they have symptoms or concerns about their disease control,” commented David Rubin, MD, who did not participate in the study.

He noted that patients are often unsure whether a new symptom is the beginning of another episode of IBD or something unrelated.

“One of the biggest challenges of having IBD is just the perception of loss of control of the disease and knowing when things are going to happen,” said Dr. Rubin, a professor of medicine and the codirector of the digestive diseases center at the University of Chicago, and the chair of the scientific advisory committee for the Crohn’s & Colitis Foundation. “I often explain to people that using a tool like this would be similar to patients with diabetes checking their blood sugar – getting a feel for what’s actually happening closer to the time that it’s happening, rather than waiting for it to progress. I really think that the general idea of home monitoring is going to be a major advance in our field.”

Although the new study proved the technique’s acceptability and efficacy, it isn’t without pitfalls, according to Dr. Rubin. False positives or negatives are a concern, and other factors might influence the results. For example, proton pump inhibitors can increase FC levels. Another concern is that some patients can become obsessed with their FC levels, and may want to test themselves at any sign of illness. They may develop unrealistic expectations about the impact of medications on their FC levels.

“That’s going to open up a whole dialogue with people, so that we all are on the same page about it. But I think that the benefits of having this far outweigh those potential risks,” said Dr. Rubin.

The authors reported no conflicts of interest. Dr. Rubin has consulted for TECHLAB.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.