Mental Health

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

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

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

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

Bacterial and nonbacterial components of the gut microbiome and their function can accurately differentiate children with autism spectrum disorder (ASD) from neurotypical children, new research shows. 

The findings could form the basis for development of a noninvasive diagnostic test for ASD and also provide novel therapeutic targets, wrote investigators, led by Siew C. Ng, MBBS, PhD, with the Microbiota I-Center (MagIC), the Chinese University of Hong Kong.

Their study was published online in Nature Microbiology. 
 

Beyond Bacteria

The gut microbiome has been shown to play a central role in modulating the gut-brain axis, potentially influencing the development of ASD. 

However, most studies in ASD have focused on the bacterial component of the microbiome. Whether nonbacterial microorganisms (such as gut archaea, fungi, and viruses) or function of the gut microbiome are altered in ASD remains unclear. 

To investigate, the researchers performed metagenomic sequencing on fecal samples from 1627 boys and girls aged 1-13 years with and without ASD from five cohorts in China. 

After controlling for diet, medication, and comorbidity, they identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways that were altered in children with ASD. 

Machine-learning models using single-kingdom panels (archaea, bacteria, fungi, viruses) achieved area under the curve (AUC) values ranging from 0.68 to 0.87 in differentiating children with ASD from neurotypical control children. 

A model based on a panel of 31 multikingdom and functional markers achieved “high predictive value” for ASD, achieving an AUC of 0.91, with comparable performance among boys and girls. 

“The reproducible performance of the models across ages, sexes, and cohorts highlights their potential as promising diagnostic tools for ASD,” the investigators wrote. 

They also noted that the accuracy of the model was largely driven by the biosynthesis pathways of ubiquinol-7 and thiamine diphosphate, which were less abundant in children with ASD, and may serve as therapeutic targets. 
 

‘Exciting’ Possibilities 

“This study broadens our understanding by including fungi, archaea, and viruses, where previous studies have largely focused on the role of gut bacteria in autism,” Bhismadev Chakrabarti, PhD, research director of the Centre for Autism at the University of Reading, United Kingdom, said in a statement from the nonprofit UK Science Media Centre. 

“The results are broadly in line with previous studies that show reduced microbial diversity in autistic individuals. It also examines one of the largest samples seen in a study like this, which further strengthens the results,” Dr. Chakrabarti added. 

He said this research may provide “new ways of detecting autism, if microbial markers turn out to strengthen the ability of genetic and behavioral tests to detect autism. A future platform that can combine genetic, microbial, and simple behavioral assessments could help address the detection gap.

“One limitation of this data is that it cannot assess any causal role for the microbiota in the development of autism,” Dr. Chakrabarti noted. 

This study was supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China, The D. H. Chen Foundation, and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program. Dr. Ng has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie; has received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; is a scientific cofounder and shareholder of GenieBiome; receives patent royalties through her affiliated institutions; and is named as a co-inventor of patent applications that cover the therapeutic and diagnostic use of microbiome. Dr. Chakrabarti has no relevant conflicts of interest.
 

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

It is a great day when a patient shows up at clinical appointment already motivated to make lifestyle behavior changes. Often, they have been inspired by health information they consumed elsewhere, such as from a book, movie, documentary, TV show, a friend, or something out in the community.

Currently, one of the more public representations of health and longevity promotion is Blue Zones. The organization, named for specific areas of the world — the so-called blue zones, where people experience less disease and live longer lives — has created considerable public awareness for healthy living. Today, there are more than 75 Blue Zones Project communities across the United States, where community leaders, businesses, organizations, and citizens collaborate to make healthier choices the easier choices. A recent Netflix special, Live to 100: Secrets of the Blue Zones, further propelled blue zones into the public consciousness.

For clinicians trained in lifestyle medicine, Blue Zones’ consumer awareness is an opportunity. There is considerable crossover between the lifestyle habits advocated by Blue Zones, known as the Power9, and the six pillars of lifestyle medicine. The Blue Zones emphasis on “plant-slant” diet, natural movement, purpose and contribution, downshifting, and family and community intersect with the lifestyle medicine pillars of whole-food, plant-predominant eating patterns, regular physical activity, stress management, restorative sleep, and positive social connections. Both Blue Zones and lifestyle medicine share a goal of creating healthier and stronger individuals and communities.

For those reasons, it made perfect sense that Blue Zones and the American College of Lifestyle Medicine (ACLM) recently announced a partnership to synergize both organizations’ strengths and resources. Among other things, the collaboration will establish a new certification status of Blue Zones–Certified Physician or Blue Zones–Certified Healthcare Professional, available in 2025 exclusively to clinicians who already are or become certified in lifestyle medicine.

Because of Blue Zones’ considerable consumer awareness, physicians and other health professionals who earn the certification will stand out to potential patients as clinicians with the training and knowledge to help them make sustainable lifestyle behavior changes. A challenging part of any clinician’s job is educating and convincing patients on the proven health benefits of lifestyle behavior change within the time restraints of a routine clinical visit. Patients familiar with Blue Zones are more likely to arrive already interested in changing lifestyle behavior, and clinicians should have the skills to help them achieve their goals.

In addition, community infrastructure developed through Blue Zones that supports healthful lifestyle choices is significant for patients. Lack of resources in their home, work, and community environments is a common obstacle that patients cite when discussing lifestyle change with a clinician. Bicycle lanes for commuting, parks with exercise equipment, accessible healthy food options, and community events to facilitate positive social connections enhance lifestyle-medicine prescriptions. Workplaces, restaurants, places of worship, and grocery stores are examples of community stakeholders that collaborate in Blue Zones communities to promote healthy lifestyle decisions. Although lifestyle medicine clinicians can and do identify creative ways to support patients in communities without strong healthy choice infrastructure, the Blue Zones road map is a welcome companion.

The timing is right for this synthesis of Blue Zones and lifestyle medicine. As consumer interest in Blue Zones has risen, so has clinician interest in evidence-based lifestyle medicine. Since certification in lifestyle medicine began in 2017, almost 6700 physicians and other health professionals have become certified worldwide. More than 43,000 health care professionals have registered for ACLM’s complimentary lifestyle and food-as-medicine courses highlighted by the White House Conference on Hunger, Nutrition, and Health. 

What if more patients came to us motivated to make lifestyle changes because of awareness infused in their work and supported in their surrounding community? Matching lifestyle medicine certification with Blue Zone communities equips clinicians to help these patients achieve what they really want: to live longer and better.

Dr. Collings is Director of Lifestyle Medicine, Silicon Valley Medical Development, and Past President, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It is a great day when a patient shows up at clinical appointment already motivated to make lifestyle behavior changes. Often, they have been inspired by health information they consumed elsewhere, such as from a book, movie, documentary, TV show, a friend, or something out in the community.

Currently, one of the more public representations of health and longevity promotion is Blue Zones. The organization, named for specific areas of the world — the so-called blue zones, where people experience less disease and live longer lives — has created considerable public awareness for healthy living. Today, there are more than 75 Blue Zones Project communities across the United States, where community leaders, businesses, organizations, and citizens collaborate to make healthier choices the easier choices. A recent Netflix special, Live to 100: Secrets of the Blue Zones, further propelled blue zones into the public consciousness.

For clinicians trained in lifestyle medicine, Blue Zones’ consumer awareness is an opportunity. There is considerable crossover between the lifestyle habits advocated by Blue Zones, known as the Power9, and the six pillars of lifestyle medicine. The Blue Zones emphasis on “plant-slant” diet, natural movement, purpose and contribution, downshifting, and family and community intersect with the lifestyle medicine pillars of whole-food, plant-predominant eating patterns, regular physical activity, stress management, restorative sleep, and positive social connections. Both Blue Zones and lifestyle medicine share a goal of creating healthier and stronger individuals and communities.

For those reasons, it made perfect sense that Blue Zones and the American College of Lifestyle Medicine (ACLM) recently announced a partnership to synergize both organizations’ strengths and resources. Among other things, the collaboration will establish a new certification status of Blue Zones–Certified Physician or Blue Zones–Certified Healthcare Professional, available in 2025 exclusively to clinicians who already are or become certified in lifestyle medicine.

Because of Blue Zones’ considerable consumer awareness, physicians and other health professionals who earn the certification will stand out to potential patients as clinicians with the training and knowledge to help them make sustainable lifestyle behavior changes. A challenging part of any clinician’s job is educating and convincing patients on the proven health benefits of lifestyle behavior change within the time restraints of a routine clinical visit. Patients familiar with Blue Zones are more likely to arrive already interested in changing lifestyle behavior, and clinicians should have the skills to help them achieve their goals.

In addition, community infrastructure developed through Blue Zones that supports healthful lifestyle choices is significant for patients. Lack of resources in their home, work, and community environments is a common obstacle that patients cite when discussing lifestyle change with a clinician. Bicycle lanes for commuting, parks with exercise equipment, accessible healthy food options, and community events to facilitate positive social connections enhance lifestyle-medicine prescriptions. Workplaces, restaurants, places of worship, and grocery stores are examples of community stakeholders that collaborate in Blue Zones communities to promote healthy lifestyle decisions. Although lifestyle medicine clinicians can and do identify creative ways to support patients in communities without strong healthy choice infrastructure, the Blue Zones road map is a welcome companion.

The timing is right for this synthesis of Blue Zones and lifestyle medicine. As consumer interest in Blue Zones has risen, so has clinician interest in evidence-based lifestyle medicine. Since certification in lifestyle medicine began in 2017, almost 6700 physicians and other health professionals have become certified worldwide. More than 43,000 health care professionals have registered for ACLM’s complimentary lifestyle and food-as-medicine courses highlighted by the White House Conference on Hunger, Nutrition, and Health. 

What if more patients came to us motivated to make lifestyle changes because of awareness infused in their work and supported in their surrounding community? Matching lifestyle medicine certification with Blue Zone communities equips clinicians to help these patients achieve what they really want: to live longer and better.

Dr. Collings is Director of Lifestyle Medicine, Silicon Valley Medical Development, and Past President, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It is a great day when a patient shows up at clinical appointment already motivated to make lifestyle behavior changes. Often, they have been inspired by health information they consumed elsewhere, such as from a book, movie, documentary, TV show, a friend, or something out in the community.

Currently, one of the more public representations of health and longevity promotion is Blue Zones. The organization, named for specific areas of the world — the so-called blue zones, where people experience less disease and live longer lives — has created considerable public awareness for healthy living. Today, there are more than 75 Blue Zones Project communities across the United States, where community leaders, businesses, organizations, and citizens collaborate to make healthier choices the easier choices. A recent Netflix special, Live to 100: Secrets of the Blue Zones, further propelled blue zones into the public consciousness.

For clinicians trained in lifestyle medicine, Blue Zones’ consumer awareness is an opportunity. There is considerable crossover between the lifestyle habits advocated by Blue Zones, known as the Power9, and the six pillars of lifestyle medicine. The Blue Zones emphasis on “plant-slant” diet, natural movement, purpose and contribution, downshifting, and family and community intersect with the lifestyle medicine pillars of whole-food, plant-predominant eating patterns, regular physical activity, stress management, restorative sleep, and positive social connections. Both Blue Zones and lifestyle medicine share a goal of creating healthier and stronger individuals and communities.

For those reasons, it made perfect sense that Blue Zones and the American College of Lifestyle Medicine (ACLM) recently announced a partnership to synergize both organizations’ strengths and resources. Among other things, the collaboration will establish a new certification status of Blue Zones–Certified Physician or Blue Zones–Certified Healthcare Professional, available in 2025 exclusively to clinicians who already are or become certified in lifestyle medicine.

Because of Blue Zones’ considerable consumer awareness, physicians and other health professionals who earn the certification will stand out to potential patients as clinicians with the training and knowledge to help them make sustainable lifestyle behavior changes. A challenging part of any clinician’s job is educating and convincing patients on the proven health benefits of lifestyle behavior change within the time restraints of a routine clinical visit. Patients familiar with Blue Zones are more likely to arrive already interested in changing lifestyle behavior, and clinicians should have the skills to help them achieve their goals.

In addition, community infrastructure developed through Blue Zones that supports healthful lifestyle choices is significant for patients. Lack of resources in their home, work, and community environments is a common obstacle that patients cite when discussing lifestyle change with a clinician. Bicycle lanes for commuting, parks with exercise equipment, accessible healthy food options, and community events to facilitate positive social connections enhance lifestyle-medicine prescriptions. Workplaces, restaurants, places of worship, and grocery stores are examples of community stakeholders that collaborate in Blue Zones communities to promote healthy lifestyle decisions. Although lifestyle medicine clinicians can and do identify creative ways to support patients in communities without strong healthy choice infrastructure, the Blue Zones road map is a welcome companion.

The timing is right for this synthesis of Blue Zones and lifestyle medicine. As consumer interest in Blue Zones has risen, so has clinician interest in evidence-based lifestyle medicine. Since certification in lifestyle medicine began in 2017, almost 6700 physicians and other health professionals have become certified worldwide. More than 43,000 health care professionals have registered for ACLM’s complimentary lifestyle and food-as-medicine courses highlighted by the White House Conference on Hunger, Nutrition, and Health. 

What if more patients came to us motivated to make lifestyle changes because of awareness infused in their work and supported in their surrounding community? Matching lifestyle medicine certification with Blue Zone communities equips clinicians to help these patients achieve what they really want: to live longer and better.

Dr. Collings is Director of Lifestyle Medicine, Silicon Valley Medical Development, and Past President, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

TOPLINE:

High-dose antipsychotics, particularly quetiapine, clozapine, and olanzapine, are linked to increased pneumonia risk in patients with schizophrenia, new data show. Monotherapy with high anticholinergic burden also raises pneumonia risk.

METHODOLOGY: 

• Using several nationwide data registers, investigators pulled data on individuals who received inpatient care for schizophrenia or schizoaffective disorder (n = 61,889) between 1972 and 2014.
• Data on drug use were gathered from a prescription register and included dispensing dates, cost, dose, package size, and drug formulation. Data on dates and causes of death were obtained from the Causes of Death register.
• After entering the cohort, follow-up started in January 1996 or after the first diagnosis of schizophrenia for those diagnosed between 1996 and 2014.
• The primary outcome was hospitalization caused by pneumonia as the main diagnosis for hospital admission.

TAKEAWAY: 

• During 22 years of follow-up, 8917 patients (14.4%) had one or more hospitalizations for pneumonia, and 1137 (12.8%) died within 30 days of admission.
• Pneumonia risk was the highest with the use of high-dose (> 440 mg/d) quetiapine (P = .003), followed by high- (≥ 330 mg/d) and medium-dose (180 to < 330 mg/d) clozapine (both P < .001) and high-dose (≥ 11 mg/d) olanzapine (P = .02).
• Compared with no antipsychotic use, antipsychotic monotherapy was associated with an increased pneumonia risk (P = .03), whereas antipsychotic polytherapy was not.
• Only the use of antipsychotics with high anticholinergic potency was associated with pneumonia risk (P < .001).

IN PRACTICE:

“Identification of antipsychotic drugs that are associated with pneumonia risk may better inform prevention programs (eg, vaccinations),” the researchers noted. “Second, the availability of pneumonia risk estimates for individual antipsychotics and for groups of antipsychotics may foster personalized prescribing guidelines.”

SOURCE:

The study was led by Jurjen Luykx, MD, Amsterdam University Medical Center, Amsterdam, the Netherlands. It was published online in JAMA Psychiatry.

LIMITATIONS:

The investigators could not correct for all possible risk factors that may increase pneumonia risk in individuals with schizophrenia, such as smoking and lifestyle habits. Also, cases of pneumonia that didn’t require hospital admission couldn’t be included in the analysis, so the findings may generalize only to cases of severe pneumonia.

DISCLOSURES:

The study was funded by the Finnish Ministry of Social Affairs and Health.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

High-dose antipsychotics, particularly quetiapine, clozapine, and olanzapine, are linked to increased pneumonia risk in patients with schizophrenia, new data show. Monotherapy with high anticholinergic burden also raises pneumonia risk.

METHODOLOGY: 

• Using several nationwide data registers, investigators pulled data on individuals who received inpatient care for schizophrenia or schizoaffective disorder (n = 61,889) between 1972 and 2014.
• Data on drug use were gathered from a prescription register and included dispensing dates, cost, dose, package size, and drug formulation. Data on dates and causes of death were obtained from the Causes of Death register.
• After entering the cohort, follow-up started in January 1996 or after the first diagnosis of schizophrenia for those diagnosed between 1996 and 2014.
• The primary outcome was hospitalization caused by pneumonia as the main diagnosis for hospital admission.

TAKEAWAY: 

• During 22 years of follow-up, 8917 patients (14.4%) had one or more hospitalizations for pneumonia, and 1137 (12.8%) died within 30 days of admission.
• Pneumonia risk was the highest with the use of high-dose (> 440 mg/d) quetiapine (P = .003), followed by high- (≥ 330 mg/d) and medium-dose (180 to < 330 mg/d) clozapine (both P < .001) and high-dose (≥ 11 mg/d) olanzapine (P = .02).
• Compared with no antipsychotic use, antipsychotic monotherapy was associated with an increased pneumonia risk (P = .03), whereas antipsychotic polytherapy was not.
• Only the use of antipsychotics with high anticholinergic potency was associated with pneumonia risk (P < .001).

IN PRACTICE:

“Identification of antipsychotic drugs that are associated with pneumonia risk may better inform prevention programs (eg, vaccinations),” the researchers noted. “Second, the availability of pneumonia risk estimates for individual antipsychotics and for groups of antipsychotics may foster personalized prescribing guidelines.”

SOURCE:

The study was led by Jurjen Luykx, MD, Amsterdam University Medical Center, Amsterdam, the Netherlands. It was published online in JAMA Psychiatry.

LIMITATIONS:

The investigators could not correct for all possible risk factors that may increase pneumonia risk in individuals with schizophrenia, such as smoking and lifestyle habits. Also, cases of pneumonia that didn’t require hospital admission couldn’t be included in the analysis, so the findings may generalize only to cases of severe pneumonia.

DISCLOSURES:

The study was funded by the Finnish Ministry of Social Affairs and Health.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

High-dose antipsychotics, particularly quetiapine, clozapine, and olanzapine, are linked to increased pneumonia risk in patients with schizophrenia, new data show. Monotherapy with high anticholinergic burden also raises pneumonia risk.

METHODOLOGY: 

• Using several nationwide data registers, investigators pulled data on individuals who received inpatient care for schizophrenia or schizoaffective disorder (n = 61,889) between 1972 and 2014.
• Data on drug use were gathered from a prescription register and included dispensing dates, cost, dose, package size, and drug formulation. Data on dates and causes of death were obtained from the Causes of Death register.
• After entering the cohort, follow-up started in January 1996 or after the first diagnosis of schizophrenia for those diagnosed between 1996 and 2014.
• The primary outcome was hospitalization caused by pneumonia as the main diagnosis for hospital admission.

TAKEAWAY: 

• During 22 years of follow-up, 8917 patients (14.4%) had one or more hospitalizations for pneumonia, and 1137 (12.8%) died within 30 days of admission.
• Pneumonia risk was the highest with the use of high-dose (> 440 mg/d) quetiapine (P = .003), followed by high- (≥ 330 mg/d) and medium-dose (180 to < 330 mg/d) clozapine (both P < .001) and high-dose (≥ 11 mg/d) olanzapine (P = .02).
• Compared with no antipsychotic use, antipsychotic monotherapy was associated with an increased pneumonia risk (P = .03), whereas antipsychotic polytherapy was not.
• Only the use of antipsychotics with high anticholinergic potency was associated with pneumonia risk (P < .001).

IN PRACTICE:

“Identification of antipsychotic drugs that are associated with pneumonia risk may better inform prevention programs (eg, vaccinations),” the researchers noted. “Second, the availability of pneumonia risk estimates for individual antipsychotics and for groups of antipsychotics may foster personalized prescribing guidelines.”

SOURCE:

The study was led by Jurjen Luykx, MD, Amsterdam University Medical Center, Amsterdam, the Netherlands. It was published online in JAMA Psychiatry.

LIMITATIONS:

The investigators could not correct for all possible risk factors that may increase pneumonia risk in individuals with schizophrenia, such as smoking and lifestyle habits. Also, cases of pneumonia that didn’t require hospital admission couldn’t be included in the analysis, so the findings may generalize only to cases of severe pneumonia.

DISCLOSURES:

The study was funded by the Finnish Ministry of Social Affairs and Health.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

Clinical Case: Sol is a 10 year-old cisgender White girl who appears sad at her annual well visit. On further inquiry she describes that her father is angry that there is no snow, her mother keeps talking about the forests disappearing, and local flooding closed down her favorite family restaurant for good. She is worried “the planet is in trouble and there’s nothing we can do” so much that she gets stomachaches when she thinks about it.

Climate Anxiety

Climate change is a complex phenomenon that has been subject to decades of political disagreement. Lobbying by groups like the fossil fuel industry, state legislation to implement recycling, oil spills and pollution disasters, and outspoken icons like former US Vice President Al Gore and Swedish activist Greta Thunberg have kept the climate crisis a hot topic. What was once a slow burn has begun to boil as climate-related disasters occur — wildfires, droughts, floods, and increasingly powerful and frequent severe weather events — alongside increasing temperatures globally. With heroic efforts, the UN-convened Paris Agreement was adopted by 196 nations in 2015 with ambitious goals to reduce global greenhouse emissions and limit Earth’s rising temperature.¹ Yet doomsday headlines on this topic remain a regular occurrence.

Between sensationalized news coverage, political controversy, and international disasters, it is no wonder some youth are overwhelmed. When it comes to the effects of climate change on youth mental health, there are direct and indirect consequences.² Direct effects could include a family losing their home to flooding or wildfires, resulting in post-traumatic stress symptoms or an anxiety disorder. Indirect effects might include a drought that results in loss of agricultural income leading to a forced migration, family stress and/or separation, and disordered substance use.

Managing Climate Anxiety

Climate anxiety presents with many of the typical features of other anxieties. These include worries that cycle repetitively and intrusively through the mind, somatic distress such as headaches or stomachaches, and avoidance of things that remind one of the uncertainty and distress associated with climate change. Because the climate crisis is so global and complex, hopelessness and fatigue are not uncommon.

However, climate anxiety can often be ameliorated with the typical approaches to treating anxiety. Borrowing from cognitive-behavioral and mindfulness-based interventions, many recommendations have been offered to help with eco-anxiety. External validation of youth’s concerns and fears is a starting point that might build a teen’s capacity to tolerate distressing emotions about global warming.

Once reactions to climate change are acknowledged and accepted, space is created for reflection. This might include a balance of hope and pragmatic action. For example, renewable energy sources have made up an increasing share of the market over time with the world adding 50% more renewable capacity in 2023.⁷ Seventy-two percent of Americans acknowledge global warming, 75% feel schools should teach about consequences and solutions for global warming, and 79% support investment in renewable energy.⁸

Climate activism itself has been shown to buffer climate anxiety, particularly when implemented collectively rather than individually.⁴ Nature connectedness, or cognitive and emotional connections with nature, not only has many direct mental health benefits, but is also associated with climate activism.⁹ Many other integrative interventions can improve well-being while reducing ecological harm. Nutrition, physical activity, mindfulness, and sleep are youth mental health interventions with a strong evidence base that also reduce the carbon footprint and pollution attributable to psychiatric pharmaceuticals. Moreover, these climate-friendly interventions can improve family-connectedness, thus boosting resilience.

Without needing to become eco-warriors, healthcare providers can model sustainable practices while caring for patients. This might include having more plants in the office, recycling and composting at work, adding solar panels to the rooftop, or joining local parks prescription programs (see mygreendoctor.org, a nonprofit owned by the Florida Medical Association).
 

Next Steps

Sol is relieved to hear that many kids her age share her family’s concerns. A conversation about how to manage distressing emotions and physical feelings leads to a referral for brief cognitive behavioral interventions. Her parents join your visit to hear her concerns. They want to begin a family plan for climate action. You recommend the books How to Change Everything: The Young Human’s Guide to Protecting the Planet and Each Other by Naomi Klein and The Parents’ Guide to Climate Revolution: 100 Ways to Build a Fossil-Free Future, Raise Empowered Kids, and Still Get a Good Night’s Sleep by Mary DeMocker.

Dr. Rosenfeld is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington.

References

1. Maizland L. Global Climate Agreements: Successes and Failures. Council on Foreign Relations. https://www.cfr.org/backgrounder/paris-global-climate-change-agreements.

2. van Nieuwenhuizen A et al. The effects of climate change on child and adolescent mental health: Clinical considerations. Curr Psychiatry Rep. 2021 Dec 7;23(12):88. doi: 10.1007/s11920-021-01296-y.

3. Window to Reach Climate Goals ‘Rapidly Closing’, UN Report Warns. United Nations. https://news.un.org/en/story/2023/09/1140527.

4. Schwartz SEO et al. Climate change anxiety and mental health: Environmental activism as buffer. Curr Psychol. 2022 Feb 28:1-14. doi: 10.1007/s12144-022-02735-6.

5. Pihkala P. Anxiety and the ecological crisis: an analysis of eco-anxiety and climate anxiety. Sustainability. 2020;12:7836. doi: 10.3390/su12197836.

6. Hickman C et al. Climate Anxiety in Children and Young People and Their Beliefs About Government Responses to Climate Change: A Global Survey. Lancet Planet Health. 2021 Dec;5(12):e863-e873. doi: 10.1016/S2542-5196(21)00278-3.

7. IEA (2021), Global Energy Review 2021, IEA, Paris. https://www.iea.org/reports/global-energy-review-2021/renewables.

8. Marlon J et al. Yale Climate Opinion Maps 2023. https://climatecommunication.yale.edu/visualizations-data/ycom-us/.

9. Thomson EE, Roach SP. The Relationships Among Nature Connectedness, Climate Anxiety, Climate Action, Climate Knowledge, and Mental Health. Front Psychol. 2023 Nov 15:14:1241400. doi: 10.3389/fpsyg.2023.1241400.

Clinical Case: Sol is a 10 year-old cisgender White girl who appears sad at her annual well visit. On further inquiry she describes that her father is angry that there is no snow, her mother keeps talking about the forests disappearing, and local flooding closed down her favorite family restaurant for good. She is worried “the planet is in trouble and there’s nothing we can do” so much that she gets stomachaches when she thinks about it.

Climate Anxiety

Climate change is a complex phenomenon that has been subject to decades of political disagreement. Lobbying by groups like the fossil fuel industry, state legislation to implement recycling, oil spills and pollution disasters, and outspoken icons like former US Vice President Al Gore and Swedish activist Greta Thunberg have kept the climate crisis a hot topic. What was once a slow burn has begun to boil as climate-related disasters occur — wildfires, droughts, floods, and increasingly powerful and frequent severe weather events — alongside increasing temperatures globally. With heroic efforts, the UN-convened Paris Agreement was adopted by 196 nations in 2015 with ambitious goals to reduce global greenhouse emissions and limit Earth’s rising temperature.¹ Yet doomsday headlines on this topic remain a regular occurrence.

Between sensationalized news coverage, political controversy, and international disasters, it is no wonder some youth are overwhelmed. When it comes to the effects of climate change on youth mental health, there are direct and indirect consequences.² Direct effects could include a family losing their home to flooding or wildfires, resulting in post-traumatic stress symptoms or an anxiety disorder. Indirect effects might include a drought that results in loss of agricultural income leading to a forced migration, family stress and/or separation, and disordered substance use.

Managing Climate Anxiety

Climate anxiety presents with many of the typical features of other anxieties. These include worries that cycle repetitively and intrusively through the mind, somatic distress such as headaches or stomachaches, and avoidance of things that remind one of the uncertainty and distress associated with climate change. Because the climate crisis is so global and complex, hopelessness and fatigue are not uncommon.

However, climate anxiety can often be ameliorated with the typical approaches to treating anxiety. Borrowing from cognitive-behavioral and mindfulness-based interventions, many recommendations have been offered to help with eco-anxiety. External validation of youth’s concerns and fears is a starting point that might build a teen’s capacity to tolerate distressing emotions about global warming.

Once reactions to climate change are acknowledged and accepted, space is created for reflection. This might include a balance of hope and pragmatic action. For example, renewable energy sources have made up an increasing share of the market over time with the world adding 50% more renewable capacity in 2023.⁷ Seventy-two percent of Americans acknowledge global warming, 75% feel schools should teach about consequences and solutions for global warming, and 79% support investment in renewable energy.⁸

Climate activism itself has been shown to buffer climate anxiety, particularly when implemented collectively rather than individually.⁴ Nature connectedness, or cognitive and emotional connections with nature, not only has many direct mental health benefits, but is also associated with climate activism.⁹ Many other integrative interventions can improve well-being while reducing ecological harm. Nutrition, physical activity, mindfulness, and sleep are youth mental health interventions with a strong evidence base that also reduce the carbon footprint and pollution attributable to psychiatric pharmaceuticals. Moreover, these climate-friendly interventions can improve family-connectedness, thus boosting resilience.

Without needing to become eco-warriors, healthcare providers can model sustainable practices while caring for patients. This might include having more plants in the office, recycling and composting at work, adding solar panels to the rooftop, or joining local parks prescription programs (see mygreendoctor.org, a nonprofit owned by the Florida Medical Association).
 

Next Steps

Sol is relieved to hear that many kids her age share her family’s concerns. A conversation about how to manage distressing emotions and physical feelings leads to a referral for brief cognitive behavioral interventions. Her parents join your visit to hear her concerns. They want to begin a family plan for climate action. You recommend the books How to Change Everything: The Young Human’s Guide to Protecting the Planet and Each Other by Naomi Klein and The Parents’ Guide to Climate Revolution: 100 Ways to Build a Fossil-Free Future, Raise Empowered Kids, and Still Get a Good Night’s Sleep by Mary DeMocker.

Dr. Rosenfeld is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington.

References

1. Maizland L. Global Climate Agreements: Successes and Failures. Council on Foreign Relations. https://www.cfr.org/backgrounder/paris-global-climate-change-agreements.

2. van Nieuwenhuizen A et al. The effects of climate change on child and adolescent mental health: Clinical considerations. Curr Psychiatry Rep. 2021 Dec 7;23(12):88. doi: 10.1007/s11920-021-01296-y.

3. Window to Reach Climate Goals ‘Rapidly Closing’, UN Report Warns. United Nations. https://news.un.org/en/story/2023/09/1140527.

4. Schwartz SEO et al. Climate change anxiety and mental health: Environmental activism as buffer. Curr Psychol. 2022 Feb 28:1-14. doi: 10.1007/s12144-022-02735-6.

5. Pihkala P. Anxiety and the ecological crisis: an analysis of eco-anxiety and climate anxiety. Sustainability. 2020;12:7836. doi: 10.3390/su12197836.

6. Hickman C et al. Climate Anxiety in Children and Young People and Their Beliefs About Government Responses to Climate Change: A Global Survey. Lancet Planet Health. 2021 Dec;5(12):e863-e873. doi: 10.1016/S2542-5196(21)00278-3.

7. IEA (2021), Global Energy Review 2021, IEA, Paris. https://www.iea.org/reports/global-energy-review-2021/renewables.

8. Marlon J et al. Yale Climate Opinion Maps 2023. https://climatecommunication.yale.edu/visualizations-data/ycom-us/.

9. Thomson EE, Roach SP. The Relationships Among Nature Connectedness, Climate Anxiety, Climate Action, Climate Knowledge, and Mental Health. Front Psychol. 2023 Nov 15:14:1241400. doi: 10.3389/fpsyg.2023.1241400.

Clinical Case: Sol is a 10 year-old cisgender White girl who appears sad at her annual well visit. On further inquiry she describes that her father is angry that there is no snow, her mother keeps talking about the forests disappearing, and local flooding closed down her favorite family restaurant for good. She is worried “the planet is in trouble and there’s nothing we can do” so much that she gets stomachaches when she thinks about it.

Climate Anxiety

Climate change is a complex phenomenon that has been subject to decades of political disagreement. Lobbying by groups like the fossil fuel industry, state legislation to implement recycling, oil spills and pollution disasters, and outspoken icons like former US Vice President Al Gore and Swedish activist Greta Thunberg have kept the climate crisis a hot topic. What was once a slow burn has begun to boil as climate-related disasters occur — wildfires, droughts, floods, and increasingly powerful and frequent severe weather events — alongside increasing temperatures globally. With heroic efforts, the UN-convened Paris Agreement was adopted by 196 nations in 2015 with ambitious goals to reduce global greenhouse emissions and limit Earth’s rising temperature.¹ Yet doomsday headlines on this topic remain a regular occurrence.

Between sensationalized news coverage, political controversy, and international disasters, it is no wonder some youth are overwhelmed. When it comes to the effects of climate change on youth mental health, there are direct and indirect consequences.² Direct effects could include a family losing their home to flooding or wildfires, resulting in post-traumatic stress symptoms or an anxiety disorder. Indirect effects might include a drought that results in loss of agricultural income leading to a forced migration, family stress and/or separation, and disordered substance use.

Managing Climate Anxiety

Climate anxiety presents with many of the typical features of other anxieties. These include worries that cycle repetitively and intrusively through the mind, somatic distress such as headaches or stomachaches, and avoidance of things that remind one of the uncertainty and distress associated with climate change. Because the climate crisis is so global and complex, hopelessness and fatigue are not uncommon.

However, climate anxiety can often be ameliorated with the typical approaches to treating anxiety. Borrowing from cognitive-behavioral and mindfulness-based interventions, many recommendations have been offered to help with eco-anxiety. External validation of youth’s concerns and fears is a starting point that might build a teen’s capacity to tolerate distressing emotions about global warming.

Once reactions to climate change are acknowledged and accepted, space is created for reflection. This might include a balance of hope and pragmatic action. For example, renewable energy sources have made up an increasing share of the market over time with the world adding 50% more renewable capacity in 2023.⁷ Seventy-two percent of Americans acknowledge global warming, 75% feel schools should teach about consequences and solutions for global warming, and 79% support investment in renewable energy.⁸

Climate activism itself has been shown to buffer climate anxiety, particularly when implemented collectively rather than individually.⁴ Nature connectedness, or cognitive and emotional connections with nature, not only has many direct mental health benefits, but is also associated with climate activism.⁹ Many other integrative interventions can improve well-being while reducing ecological harm. Nutrition, physical activity, mindfulness, and sleep are youth mental health interventions with a strong evidence base that also reduce the carbon footprint and pollution attributable to psychiatric pharmaceuticals. Moreover, these climate-friendly interventions can improve family-connectedness, thus boosting resilience.

Without needing to become eco-warriors, healthcare providers can model sustainable practices while caring for patients. This might include having more plants in the office, recycling and composting at work, adding solar panels to the rooftop, or joining local parks prescription programs (see mygreendoctor.org, a nonprofit owned by the Florida Medical Association).
 

Next Steps

Sol is relieved to hear that many kids her age share her family’s concerns. A conversation about how to manage distressing emotions and physical feelings leads to a referral for brief cognitive behavioral interventions. Her parents join your visit to hear her concerns. They want to begin a family plan for climate action. You recommend the books How to Change Everything: The Young Human’s Guide to Protecting the Planet and Each Other by Naomi Klein and The Parents’ Guide to Climate Revolution: 100 Ways to Build a Fossil-Free Future, Raise Empowered Kids, and Still Get a Good Night’s Sleep by Mary DeMocker.

Dr. Rosenfeld is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington.

References

1. Maizland L. Global Climate Agreements: Successes and Failures. Council on Foreign Relations. https://www.cfr.org/backgrounder/paris-global-climate-change-agreements.

2. van Nieuwenhuizen A et al. The effects of climate change on child and adolescent mental health: Clinical considerations. Curr Psychiatry Rep. 2021 Dec 7;23(12):88. doi: 10.1007/s11920-021-01296-y.

3. Window to Reach Climate Goals ‘Rapidly Closing’, UN Report Warns. United Nations. https://news.un.org/en/story/2023/09/1140527.

4. Schwartz SEO et al. Climate change anxiety and mental health: Environmental activism as buffer. Curr Psychol. 2022 Feb 28:1-14. doi: 10.1007/s12144-022-02735-6.

5. Pihkala P. Anxiety and the ecological crisis: an analysis of eco-anxiety and climate anxiety. Sustainability. 2020;12:7836. doi: 10.3390/su12197836.

6. Hickman C et al. Climate Anxiety in Children and Young People and Their Beliefs About Government Responses to Climate Change: A Global Survey. Lancet Planet Health. 2021 Dec;5(12):e863-e873. doi: 10.1016/S2542-5196(21)00278-3.

7. IEA (2021), Global Energy Review 2021, IEA, Paris. https://www.iea.org/reports/global-energy-review-2021/renewables.

8. Marlon J et al. Yale Climate Opinion Maps 2023. https://climatecommunication.yale.edu/visualizations-data/ycom-us/.

9. Thomson EE, Roach SP. The Relationships Among Nature Connectedness, Climate Anxiety, Climate Action, Climate Knowledge, and Mental Health. Front Psychol. 2023 Nov 15:14:1241400. doi: 10.3389/fpsyg.2023.1241400.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

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

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

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

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

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