Obesity and overweight, with or without metabolic dysregulation, pose vexing problems for many patients with mood, anxiety, or psychotic disorders. More than one-half of individuals with severe mental illnesses are obese or overweight,¹ resulting from multiple factors that may include psychiatric symptoms (eg, anergia and hyperphagia), poor dietary choices, sedentary lifestyle, underlying inflammatory processes, medical comorbidities, and iatrogenic consequences of certain medications. Unfortunately, numerous psychotropic medications can increase weight and appetite due to a variety of mechanisms, including antihistaminergic effects, direct appetite-stimulating effects, and proclivities to cause insulin resistance. While individual agents can vary, a recent review identified an overall 2-fold increased risk for rapid, significant weight gain during treatment with antipsychotics as a class.² In addition to lifestyle modifications (diet and exercise), many pharmacologic strategies have been proposed to counter iatrogenic weight gain, including appetite suppressants (eg, pro-dopaminergic agents such as phentermine, stimulants, and amantadine), pro-anorectant anticonvulsants (eg, topiramate or zonisamide), opioid receptor antagonists (eg, olanzapine/samidorphan or naltrexone) and oral hypoglycemics such as metformin. However, the magnitude of impact for most of these agents to reverse iatrogenic weight gain tends to be modest, particularly once significant weight gain (ie, ≥7% of initial body weight) has already occurred.

Pharmacologic strategies to modulate or enhance the effects of insulin hold particular importance for combatting psychotropic-associated weight gain. Insulin transports glucose from the intravascular space to end organs for fuel consumption; to varying degrees, second-generation antipsychotics (SGAs) and some other psychotropic medications can cause insulin resistance. This in turn leads to excessive storage of under­utilized glucose in the liver (glycogenesis), the potential for developing fatty liver (ie, nonalcoholic steatohepatitis), and conversion of excess carbohydrates to fatty acids and triglycerides, with subsequent storage in adipose tissue. Medications that can enhance the activity of insulin (so-called incretin mimetics) can help to overcome insulin resistance caused by SGAs (and potentially by other psychotropic medications) and essentially lead to weight loss through enhanced “fuel efficiency.”

Metformin, typically dosed up to 1,000 mg twice daily with meals, has increasingly become recognized as a first-line strategy to attenuate weight gain and glycemic dysregulation from SGAs via its ability to reduce insulin resistance. Yet meta-analyses have shown that although results are significantly better than placebo, overall long-term weight loss from metformin alone tends to be rather modest (<4 kg) and associated with a reduction in body mass index (BMI) of only approximately 1 point.³ Psychiatrists (and other clinicians who prescribe psychotropic medications that can cause weight gain or metabolic dysregulation) therefore need to become familiar with alternative or adjunctive weight loss options. The use of a relatively new class of incretin mimetics called glucagon-like peptide 1 (GLP-1) agonists (Table) has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation.

What are GLP-1 agonists?

GLP-1 is a hormone secreted by L cells in the intestinal mucosa in response to food. GLP-1 agonists reduce blood sugar by increasing insulin secretion, decreasing glucagon release (thus downregulating further increases in blood sugar), and reducing insulin resistance. GLP-1 agonists also reduce appetite by directly stimulating the satiety center and slowing gastric emptying and GI motility. In addition to GLP-1 agonism, some medications in this family (notably tirzepatide) also agonize a second hormone, glucose-dependent insulinotropic polypeptide, which can further induce insulin secretion as well as decrease stomach acid secretion, potentially delivering an even more substantial reduction in appetite and weight.

Routes of administration and FDA indications

Due to limited bioavailability, most GLP-1 agonists require subcutaneous (SC) injections (the sole exception is the Rybelsus brand of semaglutide, which comes in a daily pill form). Most are FDA-approved not specifically for weight loss but for patients with type 2 diabetes (defined as a hemoglobin A1C ≥6.5% or a fasting blood glucose level ≥126 mg/dL). Weight loss represents a secondary outcome for GLP-1 agonists FDA-approved for glycemic control in patients with type 2 diabetes. The 2 current exceptions to this classification are the Wegovy brand of semaglutide (ie, dosing of 2.4 mg) and the Saxenda brand of liraglutide, both of which carry FDA indications for chronic weight management alone (when paired with dietary and lifestyle modification) in individuals who are obese (BMI >30 kg/m²) regardless of the presence or absence of diabetes, or for persons who are overweight (BMI >27 kg/m²) and have ≥1 weight-related comorbid condition (eg, hypertension, type 2 diabetes, or dyslipidemia). Although patients at risk for diabetes (ie, prediabetes, defined as a hemoglobin A1C 5.7% to 6.4% or a fasting blood glucose level 100 to 125 mg/dL) were included in FDA registration trials of Saxenda or Wegovy, prediabetes is not an FDA indication for any GLP-1 agonist.

Data in weight loss

Most of the existing empirical data on weight loss with GLP-1 agonists come from studies of individuals who are overweight or obese, with or without type 2 diabetes, rather than from studies using these agents to counteract iatrogenic weight gain. In a retrospective cohort study of patients with type 2 diabetes, coadministration with serotonergic antidepressants (eg, citalopram/escitalopram) was associated with attenuation of the weight loss effects of GLP-1 agonists.⁴

Liraglutide currently is the sole GLP-1 agonist studied for treating SGA-associated weight gain. A 16-week randomized trial compared once-daily SC injected liraglutide vs placebo in patients with schizophrenia who incurred weight gain and prediabetes after taking olanzapine or clozapine.⁵ Significantly more patients taking liraglutide than placebo developed normal glucose tolerance (64% vs 16%), and body weight decreased by a mean of 5.3 kg.

Continue to: In studies of semaglutide...

In studies of semaglutide for overweight/obese patients with type 2 diabetes or prediabetes, clinical trials of oral semaglutide (Rybelsus) found a mean weight loss over 26 weeks of -1.0 kg with dosing at 7 mg/d and -2.6 kg with dosing at 14 mg/d.⁶ A 68-week placebo-controlled trial of semaglutide (dosed at 2.4 mg SC weekly) for overweight/obese adults who did not have diabetes yielded a -15.3 kg weight loss (vs -2.6 kg with placebo); one-half of those who received semaglutide lost 15% of their initial body weight (Figure 1A and Figure 1B).⁷ Similar findings with semaglutide 2.4 mg SC weekly (Wegovy) were observed in overweight/obese adolescents, with 73% of participants losing ≥5% of their baseline weight.⁸ A comparative randomized trial in patients with type 2 diabetes also found modestly but significantly greater weight loss with oral semaglutide than with SC liraglutide.⁹

In a 72-week study of tirzepatide specifically for weight loss in nondiabetic patients who were overweight or obese, findings were especially dramatic (Figure 2A and Figure 2B).¹⁰ An overall 15% decrease in body weight was observed with 5 mg/week dosing alongside a 19.5% decrease in body weight with 10 mg/week dosing and a 20.9% weight reduction with 15 mg/week dosing.¹⁰ As noted in Figure 2B, the observed pattern of weight loss occurred along an exponential decay curve. Notably, a comparative study of tirzepatide vs once-weekly semaglutide (1 mg) in patients with type 2 diabetes¹¹ found significantly greater dose-dependent weight loss with tirzepatide than semaglutide (-1.9 kg at 5 mg, -3.6 kg at 10 mg, and -5.5 kg at 15 mg)—although the somewhat low dosing of semaglutide may have limited its optimal possible weight loss benefit.

Tolerability

Adverse effects with GLP-1 agonists are mainly gastrointestinal (eg, nausea, vomiting, abdominal pain, diarrhea, or constipation)^5-11 and generally transient. SC administration is performed in fatty tissue of the abdomen, thigh, or upper arm; site rotation is recommended to minimize injection site pain. All GLP-1 agonists carry manufacturers’ warning and precaution statements identifying the rare potential for acute pancreatitis, acute gall bladder disease, acute kidney injury, and hypoglycemia. Animal studies also have suggested an increased, dose-dependent risk for thyroid C-cell tumors with GLP-1 agonists; this has not been observed in human trials, although postmarketing pharmacovigilance reports have identified cases of medullary thyroid carcinoma in patients who took liraglutide. A manufacturer’s boxed warning indicates that a personal or family history of medullary carcinoma of the thyroid poses a contraindication for taking semaglutide, liraglutide, or tirzepatide.

Initial evidence prompts additional questions

GLP-1 agonists represent an emerging class of novel agents that can modulate glycemic dysregulation and overweight/obesity, often with dramatic results whose magnitude rivals the efficacy of bariatric surgery. Once-weekly formulations of semaglutide (Wegovy) and daily liraglutide (Saxenda) are FDA-approved for weight loss in patients who are overweight or obese while other existing formulations are approved solely for patients with type 2 diabetes, although it is likely that broader indications for weight loss (regardless of glycemic status) are forthcoming. Targeted use of GLP-1 agonists to counteract SGA-associated weight gain is supported by a handful of preliminary reports, with additional studies likely to come. Unanswered questions include:

• When should GLP-1 agonists be considered within a treatment algorithm for iatrogenic weight gain relative to other antidote strategies such as metformin or appetite-suppressing anticonvulsants?
• How effective might GLP-1 agonists be for iatrogenic weight gain from non-SGA psychotropic medications, such as serotonergic antidepressants?
• When and how can GLP-1 agonists be safely coprescribed with other nonincretin mimetic weight loss medications?
• When should psychiatrists prescribe GLP-1 agonists, or do so collaboratively with primary care physicians or endocrinologists, particularly in patients with metabolic syndrome?

Followers of the rapidly emerging literature in this area will likely find themselves best positioned to address these and other questions about optimal management of psychotropic-induced weight gain for the patients they treat.

Bottom Line

The use of glucagon-like peptide 1 (GLP-1) agonists, a relatively new class of incretin mimetics, has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation. Preliminary reports support the potential targeted use of GLP-1 agonists to counteract weight gain associated with second-generation antipsychotics.

Related Resources

• Singh F, Allen A, Ianni A. Managing metabolic syndrome in patients with schizophrenia. Current Psychiatry. 2020;19(12):20-24,26. doi:10.12788/cp.0064
• Ard J, Fitch A, Fruh S, et al. Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv Ther. 2021;38(6):2821- 2839. doi:10.1007/s12325-021-01710-0

Drug Brand Names

Amantadine • Gocovri
Citalopram • Celexa
Clozapine • Clozaril
Escitalopram • Lexapro
Liraglutide • Victoza, Saxenda
Metformin • Glucophage
Naltrexone • ReVia
Olanzapine • Zyprexa
Olanzapine/samidorphan • Lybalvi
Phentermine • Ionamin
Semaglutide • Rybelsus, Ozempic, Wegovy
Tirzepatide • Mounjaro
Topiramate • Topamax
Zonisamide • Zonegran

Obesity and overweight, with or without metabolic dysregulation, pose vexing problems for many patients with mood, anxiety, or psychotic disorders. More than one-half of individuals with severe mental illnesses are obese or overweight,¹ resulting from multiple factors that may include psychiatric symptoms (eg, anergia and hyperphagia), poor dietary choices, sedentary lifestyle, underlying inflammatory processes, medical comorbidities, and iatrogenic consequences of certain medications. Unfortunately, numerous psychotropic medications can increase weight and appetite due to a variety of mechanisms, including antihistaminergic effects, direct appetite-stimulating effects, and proclivities to cause insulin resistance. While individual agents can vary, a recent review identified an overall 2-fold increased risk for rapid, significant weight gain during treatment with antipsychotics as a class.² In addition to lifestyle modifications (diet and exercise), many pharmacologic strategies have been proposed to counter iatrogenic weight gain, including appetite suppressants (eg, pro-dopaminergic agents such as phentermine, stimulants, and amantadine), pro-anorectant anticonvulsants (eg, topiramate or zonisamide), opioid receptor antagonists (eg, olanzapine/samidorphan or naltrexone) and oral hypoglycemics such as metformin. However, the magnitude of impact for most of these agents to reverse iatrogenic weight gain tends to be modest, particularly once significant weight gain (ie, ≥7% of initial body weight) has already occurred.

Pharmacologic strategies to modulate or enhance the effects of insulin hold particular importance for combatting psychotropic-associated weight gain. Insulin transports glucose from the intravascular space to end organs for fuel consumption; to varying degrees, second-generation antipsychotics (SGAs) and some other psychotropic medications can cause insulin resistance. This in turn leads to excessive storage of under­utilized glucose in the liver (glycogenesis), the potential for developing fatty liver (ie, nonalcoholic steatohepatitis), and conversion of excess carbohydrates to fatty acids and triglycerides, with subsequent storage in adipose tissue. Medications that can enhance the activity of insulin (so-called incretin mimetics) can help to overcome insulin resistance caused by SGAs (and potentially by other psychotropic medications) and essentially lead to weight loss through enhanced “fuel efficiency.”

Metformin, typically dosed up to 1,000 mg twice daily with meals, has increasingly become recognized as a first-line strategy to attenuate weight gain and glycemic dysregulation from SGAs via its ability to reduce insulin resistance. Yet meta-analyses have shown that although results are significantly better than placebo, overall long-term weight loss from metformin alone tends to be rather modest (<4 kg) and associated with a reduction in body mass index (BMI) of only approximately 1 point.³ Psychiatrists (and other clinicians who prescribe psychotropic medications that can cause weight gain or metabolic dysregulation) therefore need to become familiar with alternative or adjunctive weight loss options. The use of a relatively new class of incretin mimetics called glucagon-like peptide 1 (GLP-1) agonists (Table) has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation.

What are GLP-1 agonists?

GLP-1 is a hormone secreted by L cells in the intestinal mucosa in response to food. GLP-1 agonists reduce blood sugar by increasing insulin secretion, decreasing glucagon release (thus downregulating further increases in blood sugar), and reducing insulin resistance. GLP-1 agonists also reduce appetite by directly stimulating the satiety center and slowing gastric emptying and GI motility. In addition to GLP-1 agonism, some medications in this family (notably tirzepatide) also agonize a second hormone, glucose-dependent insulinotropic polypeptide, which can further induce insulin secretion as well as decrease stomach acid secretion, potentially delivering an even more substantial reduction in appetite and weight.

Routes of administration and FDA indications

Due to limited bioavailability, most GLP-1 agonists require subcutaneous (SC) injections (the sole exception is the Rybelsus brand of semaglutide, which comes in a daily pill form). Most are FDA-approved not specifically for weight loss but for patients with type 2 diabetes (defined as a hemoglobin A1C ≥6.5% or a fasting blood glucose level ≥126 mg/dL). Weight loss represents a secondary outcome for GLP-1 agonists FDA-approved for glycemic control in patients with type 2 diabetes. The 2 current exceptions to this classification are the Wegovy brand of semaglutide (ie, dosing of 2.4 mg) and the Saxenda brand of liraglutide, both of which carry FDA indications for chronic weight management alone (when paired with dietary and lifestyle modification) in individuals who are obese (BMI >30 kg/m²) regardless of the presence or absence of diabetes, or for persons who are overweight (BMI >27 kg/m²) and have ≥1 weight-related comorbid condition (eg, hypertension, type 2 diabetes, or dyslipidemia). Although patients at risk for diabetes (ie, prediabetes, defined as a hemoglobin A1C 5.7% to 6.4% or a fasting blood glucose level 100 to 125 mg/dL) were included in FDA registration trials of Saxenda or Wegovy, prediabetes is not an FDA indication for any GLP-1 agonist.

Data in weight loss

Most of the existing empirical data on weight loss with GLP-1 agonists come from studies of individuals who are overweight or obese, with or without type 2 diabetes, rather than from studies using these agents to counteract iatrogenic weight gain. In a retrospective cohort study of patients with type 2 diabetes, coadministration with serotonergic antidepressants (eg, citalopram/escitalopram) was associated with attenuation of the weight loss effects of GLP-1 agonists.⁴

Liraglutide currently is the sole GLP-1 agonist studied for treating SGA-associated weight gain. A 16-week randomized trial compared once-daily SC injected liraglutide vs placebo in patients with schizophrenia who incurred weight gain and prediabetes after taking olanzapine or clozapine.⁵ Significantly more patients taking liraglutide than placebo developed normal glucose tolerance (64% vs 16%), and body weight decreased by a mean of 5.3 kg.

Continue to: In studies of semaglutide...

In studies of semaglutide for overweight/obese patients with type 2 diabetes or prediabetes, clinical trials of oral semaglutide (Rybelsus) found a mean weight loss over 26 weeks of -1.0 kg with dosing at 7 mg/d and -2.6 kg with dosing at 14 mg/d.⁶ A 68-week placebo-controlled trial of semaglutide (dosed at 2.4 mg SC weekly) for overweight/obese adults who did not have diabetes yielded a -15.3 kg weight loss (vs -2.6 kg with placebo); one-half of those who received semaglutide lost 15% of their initial body weight (Figure 1A and Figure 1B).⁷ Similar findings with semaglutide 2.4 mg SC weekly (Wegovy) were observed in overweight/obese adolescents, with 73% of participants losing ≥5% of their baseline weight.⁸ A comparative randomized trial in patients with type 2 diabetes also found modestly but significantly greater weight loss with oral semaglutide than with SC liraglutide.⁹

In a 72-week study of tirzepatide specifically for weight loss in nondiabetic patients who were overweight or obese, findings were especially dramatic (Figure 2A and Figure 2B).¹⁰ An overall 15% decrease in body weight was observed with 5 mg/week dosing alongside a 19.5% decrease in body weight with 10 mg/week dosing and a 20.9% weight reduction with 15 mg/week dosing.¹⁰ As noted in Figure 2B, the observed pattern of weight loss occurred along an exponential decay curve. Notably, a comparative study of tirzepatide vs once-weekly semaglutide (1 mg) in patients with type 2 diabetes¹¹ found significantly greater dose-dependent weight loss with tirzepatide than semaglutide (-1.9 kg at 5 mg, -3.6 kg at 10 mg, and -5.5 kg at 15 mg)—although the somewhat low dosing of semaglutide may have limited its optimal possible weight loss benefit.

Tolerability

Adverse effects with GLP-1 agonists are mainly gastrointestinal (eg, nausea, vomiting, abdominal pain, diarrhea, or constipation)^5-11 and generally transient. SC administration is performed in fatty tissue of the abdomen, thigh, or upper arm; site rotation is recommended to minimize injection site pain. All GLP-1 agonists carry manufacturers’ warning and precaution statements identifying the rare potential for acute pancreatitis, acute gall bladder disease, acute kidney injury, and hypoglycemia. Animal studies also have suggested an increased, dose-dependent risk for thyroid C-cell tumors with GLP-1 agonists; this has not been observed in human trials, although postmarketing pharmacovigilance reports have identified cases of medullary thyroid carcinoma in patients who took liraglutide. A manufacturer’s boxed warning indicates that a personal or family history of medullary carcinoma of the thyroid poses a contraindication for taking semaglutide, liraglutide, or tirzepatide.

Initial evidence prompts additional questions

GLP-1 agonists represent an emerging class of novel agents that can modulate glycemic dysregulation and overweight/obesity, often with dramatic results whose magnitude rivals the efficacy of bariatric surgery. Once-weekly formulations of semaglutide (Wegovy) and daily liraglutide (Saxenda) are FDA-approved for weight loss in patients who are overweight or obese while other existing formulations are approved solely for patients with type 2 diabetes, although it is likely that broader indications for weight loss (regardless of glycemic status) are forthcoming. Targeted use of GLP-1 agonists to counteract SGA-associated weight gain is supported by a handful of preliminary reports, with additional studies likely to come. Unanswered questions include:

• When should GLP-1 agonists be considered within a treatment algorithm for iatrogenic weight gain relative to other antidote strategies such as metformin or appetite-suppressing anticonvulsants?
• How effective might GLP-1 agonists be for iatrogenic weight gain from non-SGA psychotropic medications, such as serotonergic antidepressants?
• When and how can GLP-1 agonists be safely coprescribed with other nonincretin mimetic weight loss medications?
• When should psychiatrists prescribe GLP-1 agonists, or do so collaboratively with primary care physicians or endocrinologists, particularly in patients with metabolic syndrome?

Followers of the rapidly emerging literature in this area will likely find themselves best positioned to address these and other questions about optimal management of psychotropic-induced weight gain for the patients they treat.

Bottom Line

The use of glucagon-like peptide 1 (GLP-1) agonists, a relatively new class of incretin mimetics, has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation. Preliminary reports support the potential targeted use of GLP-1 agonists to counteract weight gain associated with second-generation antipsychotics.

Related Resources

• Singh F, Allen A, Ianni A. Managing metabolic syndrome in patients with schizophrenia. Current Psychiatry. 2020;19(12):20-24,26. doi:10.12788/cp.0064
• Ard J, Fitch A, Fruh S, et al. Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv Ther. 2021;38(6):2821- 2839. doi:10.1007/s12325-021-01710-0

Drug Brand Names

Amantadine • Gocovri
Citalopram • Celexa
Clozapine • Clozaril
Escitalopram • Lexapro
Liraglutide • Victoza, Saxenda
Metformin • Glucophage
Naltrexone • ReVia
Olanzapine • Zyprexa
Olanzapine/samidorphan • Lybalvi
Phentermine • Ionamin
Semaglutide • Rybelsus, Ozempic, Wegovy
Tirzepatide • Mounjaro
Topiramate • Topamax
Zonisamide • Zonegran

Obesity and overweight, with or without metabolic dysregulation, pose vexing problems for many patients with mood, anxiety, or psychotic disorders. More than one-half of individuals with severe mental illnesses are obese or overweight,¹ resulting from multiple factors that may include psychiatric symptoms (eg, anergia and hyperphagia), poor dietary choices, sedentary lifestyle, underlying inflammatory processes, medical comorbidities, and iatrogenic consequences of certain medications. Unfortunately, numerous psychotropic medications can increase weight and appetite due to a variety of mechanisms, including antihistaminergic effects, direct appetite-stimulating effects, and proclivities to cause insulin resistance. While individual agents can vary, a recent review identified an overall 2-fold increased risk for rapid, significant weight gain during treatment with antipsychotics as a class.² In addition to lifestyle modifications (diet and exercise), many pharmacologic strategies have been proposed to counter iatrogenic weight gain, including appetite suppressants (eg, pro-dopaminergic agents such as phentermine, stimulants, and amantadine), pro-anorectant anticonvulsants (eg, topiramate or zonisamide), opioid receptor antagonists (eg, olanzapine/samidorphan or naltrexone) and oral hypoglycemics such as metformin. However, the magnitude of impact for most of these agents to reverse iatrogenic weight gain tends to be modest, particularly once significant weight gain (ie, ≥7% of initial body weight) has already occurred.

Pharmacologic strategies to modulate or enhance the effects of insulin hold particular importance for combatting psychotropic-associated weight gain. Insulin transports glucose from the intravascular space to end organs for fuel consumption; to varying degrees, second-generation antipsychotics (SGAs) and some other psychotropic medications can cause insulin resistance. This in turn leads to excessive storage of under­utilized glucose in the liver (glycogenesis), the potential for developing fatty liver (ie, nonalcoholic steatohepatitis), and conversion of excess carbohydrates to fatty acids and triglycerides, with subsequent storage in adipose tissue. Medications that can enhance the activity of insulin (so-called incretin mimetics) can help to overcome insulin resistance caused by SGAs (and potentially by other psychotropic medications) and essentially lead to weight loss through enhanced “fuel efficiency.”

Metformin, typically dosed up to 1,000 mg twice daily with meals, has increasingly become recognized as a first-line strategy to attenuate weight gain and glycemic dysregulation from SGAs via its ability to reduce insulin resistance. Yet meta-analyses have shown that although results are significantly better than placebo, overall long-term weight loss from metformin alone tends to be rather modest (<4 kg) and associated with a reduction in body mass index (BMI) of only approximately 1 point.³ Psychiatrists (and other clinicians who prescribe psychotropic medications that can cause weight gain or metabolic dysregulation) therefore need to become familiar with alternative or adjunctive weight loss options. The use of a relatively new class of incretin mimetics called glucagon-like peptide 1 (GLP-1) agonists (Table) has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation.

What are GLP-1 agonists?

GLP-1 is a hormone secreted by L cells in the intestinal mucosa in response to food. GLP-1 agonists reduce blood sugar by increasing insulin secretion, decreasing glucagon release (thus downregulating further increases in blood sugar), and reducing insulin resistance. GLP-1 agonists also reduce appetite by directly stimulating the satiety center and slowing gastric emptying and GI motility. In addition to GLP-1 agonism, some medications in this family (notably tirzepatide) also agonize a second hormone, glucose-dependent insulinotropic polypeptide, which can further induce insulin secretion as well as decrease stomach acid secretion, potentially delivering an even more substantial reduction in appetite and weight.

Routes of administration and FDA indications

Due to limited bioavailability, most GLP-1 agonists require subcutaneous (SC) injections (the sole exception is the Rybelsus brand of semaglutide, which comes in a daily pill form). Most are FDA-approved not specifically for weight loss but for patients with type 2 diabetes (defined as a hemoglobin A1C ≥6.5% or a fasting blood glucose level ≥126 mg/dL). Weight loss represents a secondary outcome for GLP-1 agonists FDA-approved for glycemic control in patients with type 2 diabetes. The 2 current exceptions to this classification are the Wegovy brand of semaglutide (ie, dosing of 2.4 mg) and the Saxenda brand of liraglutide, both of which carry FDA indications for chronic weight management alone (when paired with dietary and lifestyle modification) in individuals who are obese (BMI >30 kg/m²) regardless of the presence or absence of diabetes, or for persons who are overweight (BMI >27 kg/m²) and have ≥1 weight-related comorbid condition (eg, hypertension, type 2 diabetes, or dyslipidemia). Although patients at risk for diabetes (ie, prediabetes, defined as a hemoglobin A1C 5.7% to 6.4% or a fasting blood glucose level 100 to 125 mg/dL) were included in FDA registration trials of Saxenda or Wegovy, prediabetes is not an FDA indication for any GLP-1 agonist.

Data in weight loss

Most of the existing empirical data on weight loss with GLP-1 agonists come from studies of individuals who are overweight or obese, with or without type 2 diabetes, rather than from studies using these agents to counteract iatrogenic weight gain. In a retrospective cohort study of patients with type 2 diabetes, coadministration with serotonergic antidepressants (eg, citalopram/escitalopram) was associated with attenuation of the weight loss effects of GLP-1 agonists.⁴

Liraglutide currently is the sole GLP-1 agonist studied for treating SGA-associated weight gain. A 16-week randomized trial compared once-daily SC injected liraglutide vs placebo in patients with schizophrenia who incurred weight gain and prediabetes after taking olanzapine or clozapine.⁵ Significantly more patients taking liraglutide than placebo developed normal glucose tolerance (64% vs 16%), and body weight decreased by a mean of 5.3 kg.

Continue to: In studies of semaglutide...

In studies of semaglutide for overweight/obese patients with type 2 diabetes or prediabetes, clinical trials of oral semaglutide (Rybelsus) found a mean weight loss over 26 weeks of -1.0 kg with dosing at 7 mg/d and -2.6 kg with dosing at 14 mg/d.⁶ A 68-week placebo-controlled trial of semaglutide (dosed at 2.4 mg SC weekly) for overweight/obese adults who did not have diabetes yielded a -15.3 kg weight loss (vs -2.6 kg with placebo); one-half of those who received semaglutide lost 15% of their initial body weight (Figure 1A and Figure 1B).⁷ Similar findings with semaglutide 2.4 mg SC weekly (Wegovy) were observed in overweight/obese adolescents, with 73% of participants losing ≥5% of their baseline weight.⁸ A comparative randomized trial in patients with type 2 diabetes also found modestly but significantly greater weight loss with oral semaglutide than with SC liraglutide.⁹

In a 72-week study of tirzepatide specifically for weight loss in nondiabetic patients who were overweight or obese, findings were especially dramatic (Figure 2A and Figure 2B).¹⁰ An overall 15% decrease in body weight was observed with 5 mg/week dosing alongside a 19.5% decrease in body weight with 10 mg/week dosing and a 20.9% weight reduction with 15 mg/week dosing.¹⁰ As noted in Figure 2B, the observed pattern of weight loss occurred along an exponential decay curve. Notably, a comparative study of tirzepatide vs once-weekly semaglutide (1 mg) in patients with type 2 diabetes¹¹ found significantly greater dose-dependent weight loss with tirzepatide than semaglutide (-1.9 kg at 5 mg, -3.6 kg at 10 mg, and -5.5 kg at 15 mg)—although the somewhat low dosing of semaglutide may have limited its optimal possible weight loss benefit.

Tolerability

Adverse effects with GLP-1 agonists are mainly gastrointestinal (eg, nausea, vomiting, abdominal pain, diarrhea, or constipation)^5-11 and generally transient. SC administration is performed in fatty tissue of the abdomen, thigh, or upper arm; site rotation is recommended to minimize injection site pain. All GLP-1 agonists carry manufacturers’ warning and precaution statements identifying the rare potential for acute pancreatitis, acute gall bladder disease, acute kidney injury, and hypoglycemia. Animal studies also have suggested an increased, dose-dependent risk for thyroid C-cell tumors with GLP-1 agonists; this has not been observed in human trials, although postmarketing pharmacovigilance reports have identified cases of medullary thyroid carcinoma in patients who took liraglutide. A manufacturer’s boxed warning indicates that a personal or family history of medullary carcinoma of the thyroid poses a contraindication for taking semaglutide, liraglutide, or tirzepatide.

Initial evidence prompts additional questions

GLP-1 agonists represent an emerging class of novel agents that can modulate glycemic dysregulation and overweight/obesity, often with dramatic results whose magnitude rivals the efficacy of bariatric surgery. Once-weekly formulations of semaglutide (Wegovy) and daily liraglutide (Saxenda) are FDA-approved for weight loss in patients who are overweight or obese while other existing formulations are approved solely for patients with type 2 diabetes, although it is likely that broader indications for weight loss (regardless of glycemic status) are forthcoming. Targeted use of GLP-1 agonists to counteract SGA-associated weight gain is supported by a handful of preliminary reports, with additional studies likely to come. Unanswered questions include:

• When should GLP-1 agonists be considered within a treatment algorithm for iatrogenic weight gain relative to other antidote strategies such as metformin or appetite-suppressing anticonvulsants?
• How effective might GLP-1 agonists be for iatrogenic weight gain from non-SGA psychotropic medications, such as serotonergic antidepressants?
• When and how can GLP-1 agonists be safely coprescribed with other nonincretin mimetic weight loss medications?
• When should psychiatrists prescribe GLP-1 agonists, or do so collaboratively with primary care physicians or endocrinologists, particularly in patients with metabolic syndrome?

Followers of the rapidly emerging literature in this area will likely find themselves best positioned to address these and other questions about optimal management of psychotropic-induced weight gain for the patients they treat.

Bottom Line

The use of glucagon-like peptide 1 (GLP-1) agonists, a relatively new class of incretin mimetics, has been associated with profound and often dramatic weight loss and improvement of glycemic parameters in patients with obesity and glycemic dysregulation. Preliminary reports support the potential targeted use of GLP-1 agonists to counteract weight gain associated with second-generation antipsychotics.

Related Resources

• Singh F, Allen A, Ianni A. Managing metabolic syndrome in patients with schizophrenia. Current Psychiatry. 2020;19(12):20-24,26. doi:10.12788/cp.0064
• Ard J, Fitch A, Fruh S, et al. Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv Ther. 2021;38(6):2821- 2839. doi:10.1007/s12325-021-01710-0

Drug Brand Names

Amantadine • Gocovri
Citalopram • Celexa
Clozapine • Clozaril
Escitalopram • Lexapro
Liraglutide • Victoza, Saxenda
Metformin • Glucophage
Naltrexone • ReVia
Olanzapine • Zyprexa
Olanzapine/samidorphan • Lybalvi
Phentermine • Ionamin
Semaglutide • Rybelsus, Ozempic, Wegovy
Tirzepatide • Mounjaro
Topiramate • Topamax
Zonisamide • Zonegran

Catatonia is often difficult to identify and treat. The excited catatonia subtype can be particularly challenging to diagnose because it can present with symptoms similar to those seen in mania or psychosis. In this article, we present 3 cases of excited catatonia that illustrate how to identify it, how to treat the catatonia as well as the underlying pathology, and factors to consider during this process to mitigate the risk of adverse outcomes. We also outline a treatment algorithm we used for the 3 cases. Although we describe using this approach for patients with excited catatonia, it is generalizable to other types of catatonia.

Many causes, varying presentations

Catatonia is a psychomotor syndrome characterized by mutism, negativism, stereotypy, waxy flexibility, and other symptoms.¹ It is defined by the presence of ≥3 of the 12 symptoms listed in the Table.² Causes of catatonia include metabolic abnormalities, endocrine disorders, drug intoxication, neurodevelopmental disorders, medication adverse effects, psychosis, and mood disorders.^1,3

A subtype of this syndrome, excited catatonia, can present with restlessness, agitation, emotional lability, poor sleep, and altered mental status in addition to the more typical symptoms.^1,4 Because excited catatonia can resemble mania or psychosis, it is particularly challenging to identify the underlying disorder causing it and appropriate treatment. Fink et al⁴ discussed how clinicians have interpreted the different presentations of excited catatonia to gain insight into the underlying diagnosis. If the patient’s thought process appears disorganized, psychosis may be suspected.⁴ If the patient is delusional and grandiose, they may be manic, and when altered mental status dominates the presentation, delirium may be the culprit.⁴

Regardless of the underlying cause, the first step is to treat the catatonia. Benzodiazepines and electroconvulsive therapy (ECT) are the most well validated treatments for catatonia and have been used to treat excited catatonia.¹ Excited catatonia is often misdiagnosed and subsequently mistreated. In the following 3 cases, excited catatonia was successfully identified and treated using the same approach (Figure).

Case 1

Mr. A, age 27, has a history of bipolar I disorder. He was brought to the hospital by ambulance after being found to be yelling and acting belligerently, and he was admitted to the inpatient psychiatry unit for manic decompensation due to medication nonadherence. He was started on divalproex sodium 500 mg twice a day for mood stabilization, risperidone 1 mg twice a day for adjunct mood stabilization and psychosis, and lorazepam 1 mg 3 times a day for agitation. Mr. A exhibited odd behavior; he would take off his clothes in the hallway, run around the unit, and randomly yell at staff or to himself. At other times, he would stay silent, repeat the same statements, or oddly posture in the hallway for minutes at a time. These behaviors were seen primarily in the hour or 2 preceding lorazepam administration and improved after he received lorazepam.

Mr. A’s treating team completed the Bush-Francis Catatonia Rating Scale (BFCRS), which yielded a positive catatonia screen of 7/14. As a result, divalproex sodium and risperidone were held, and lorazepam was increased to 2 mg twice a day.

After several days, Mr. A was no longer acting oddly and was able to speak more spontaneously; however, he began to exhibit overt signs of mania. He would speak rapidly and make grandiose claims about managing millions of dollars as the CEO of a famous company. Divalproex sodium was restarted at 500 mg twice a day and increased to 500 mg 3 times a day for mood stabilization. Mr. A continued to receive lorazepam 2 mg 3 times a day for catatonia, and risperidone was restarted at 1 mg twice a day to more effectively target his manic symptoms. Risperidone was increased to 2 mg twice a day. After this change, Mr. A’s grandiosity dissipated, his speech normalized, and his thought process became organized. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium 500 mg 3 times a day, and risperidone 2 mg twice a day. Mr. A’s length of stay (LOS) for this admission was 11 days.

Continue to: Case 2

Case 2

Mr. B, age 49, presented with irritability and odd posturing. He has a history of schizoaffective disorder, bipolar type for which he was receiving a maintenance regimen of lithium 600 mg/d at bedtime and risperidone 2 mg/d at bedtime. He had multiple previous psychiatric admissions for catatonia. On this admission, Mr. B was irritable and difficult to redirect. He yelled at staff members and had a stiff gait. The BFCRS yielded a positive screening score of 3/14 and a severity score of 8/23. As a result, the treatment team conducted a lorazepam challenge.

After Mr. B received lorazepam 1 mg IM, his thought organization and irritability improved, which allowed him to have a coherent conversation with the interviewer. His gait stiffness also improved. His risperidone and lithium were held, and oral lorazepam 1 mg 3 times a day was started for catatonia. Lorazepam was gradually increased to 4 mg 3 times a day. Mr. B became euthymic and redirectable, and had an improved gait. However, he was also tangential and hyperverbal; these symptoms were indicative of the underlying mania that precipitated his catatonia.

Divalproex sodium extended release (ER) was started and increased to 1,500 mg/d at bedtime for mood stabilization. Lithium was restarted and increased to 300 mg twice a day for adjunct mood stabilization. Risperidone was not restarted. Toward the end of his admission, Mr. B was noted to be overly sedated, so the lorazepam dosage was decreased. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium ER 1,500 mg/d at bedtime, and lithium 300 mg twice a day. At discharge, Mr. B was calm and euthymic, with a linear thought process. His LOS was 25 days.

Case 3

Mr. C, age 62, presented to the emergency department (ED) because he had exhibited erratic behavior and had not slept for the past week. He has a history of bipolar I disorder, hypothyroidism, diabetes, and hypertension. For many years, he had been stable on divalproex sodium ER 2,500 mg/d at bedtime for mood stabilization and clozapine 100 mg/d at bedtime for adjunct mood stabilization and psychosis. In the ED, Mr. C was irritable, distractible, and tangential. On admission, he was speaking slowly with increased speech latency in response to questions, exhibiting stereotypy, repeating statements over and over, and walking very slowly.

The BFCRS yielded a positive screening score of 5/14 and a severity score of 10/23. Lorazepam 1 mg IM was administered. After 15 minutes, Mr. C’s speech, gait, and distractibility improved. As a result, clozapine and divalproex sodium were held, and he was started on oral lorazepam 1 mg 3 times a day. After several days, Mr. C was speaking fluently and no longer exhibiting stereotypy or having outbursts where he would make repetitive statements. However, he was tangential and irritable at times, which were signs of his underlying mania. Divalproex sodium ER was restarted at 250 mg/d at bedtime for mood stabilization and gradually increased to 2,500 mg/d at bedtime. Clozapine was also restarted at 25 mg/d at bedtime and gradually increased to 200 mg/d at bedtime. The lorazepam was gradually tapered and discontinued over the course of 3 weeks due to oversedation.

Continue to: At discharge...

At discharge, Mr. C was euthymic, calm, linear, and goal-directed. He was discharged on divalproex sodium ER 2,500 mg/d at bedtime and clozapine 200 mg/d at bedtime. His LOS for this admission was 22 days.

A stepwise approach can improve outcomes

The Figure outlines the method we used to manage excited catatonia in these 3 cases. Each of these patients exhibited signs of excited catatonia, but because those symptoms were nearly identical to those of mania, it was initially difficult to identify catatonia. Excited catatonia was suspected after more typical catatonic symptoms—such as a stiff gait, slowed speech, and stereotypy—were observed. The BFCRS was completed to get an objective measure of the likelihood that the patient was catatonic. In all 3 cases, the BFCRS resulted in a positive screen for catatonia. Following this, the patients described in Case 2 and Case 3 received a lorazepam challenge, which confirmed their catatonia. No lorazepam challenge was performed in Case 1 because the patient was already receiving lorazepam when the BFCRS was completed. Although most catatonic patients will respond to a lorazepam challenge, not all will. Therefore, clinicians should maintain some degree of suspicion for catatonia if a patient has a positive screen on the BFCRS but a negative lorazepam challenge.

In all 3 cases, after catatonia was confirmed, the patient’s psychotropic medications were discontinued. In all 3 cases, the antipsychotic was held to prevent progression to neuroleptic malignant syndrome (NMS) or malignant catatonia. Rasmussen et al³ found that 3.6% of the catatonic patients in their sample who were treated with antipsychotics developed NMS. A review of prospective studies looking at patients treated with antipsychotics found the incidence of NMS was .07% to 1.8%.⁵ Because NMS is often clinically indistinguishable from malignant catatonia,^4,6 this incidence of NMS may have represented an increased incidence in malignant catatonia.

In all 3 cases, the mood stabilizer was held to prevent it from complicating the clinical picture. Discontinuing the mood stabilizer and focusing on treating the catatonia before targeting the underlying mania increased the likelihood of differentiating the patient’s catatonic symptoms from manic symptoms. This resulted in more precise medication selection and titration by allowing us to identify the specific symptoms that were being targeted by each medication.

Oral lorazepam was prescribed to target catatonia in all 3 cases, and the dosage was gradually increased until symptoms began to resolve. As the catatonia resolved, the manic symptoms became more easily identifiable, and at this point a mood stabilizer was started and titrated to a therapeutic dose to target the mania. In Case 1 and Case 3, the antipsychotic was restarted to treat the mania more effectively. It was not restarted in Case 2 because the patient’s mania was effectively being managed by 2 mood stabilizers. The risks and benefits of starting an antipsychotic in a catatonic or recently catatonic patient should be carefully considered. In the 2 cases where the antipsychotic was restarted, the patients were closely monitored, and there were no signs of NMS or malignant catatonia.

Continue to: As discharge approached...

As discharge approached, the dosages of oral lorazepam were reevaluated. Catatonic patients can typically tolerate high doses of benzodiazepines without becoming overly sedated, but each patient has a different threshold at which the dosage causes oversedation. In all 3 patients, lorazepam was initially titrated to a dose that treated their catatonic symptoms without causing intolerable sedation. In Case 2 and Case 3, as the catatonia began to resolve, the patients became increasingly sedated on their existing lorazepam dosage, so it was decreased. Because the patient in Case 1 did not become overly sedated, his lorazepam dosage did not need to be reduced.

For 2 of these patients, our approach resulted in a shorter LOS compared to their previous hospitalizations. The LOS in Case 2 was 25 days; 5 years earlier, he had a 49-day LOS for mania and catatonia. During the past admission, the identification and treatment of the catatonia was delayed, which resulted in the patient requiring multiple transfers to the medical unit for unstable vital signs. The LOS in Case 3 was 22 days; 6 months prior to this admission, the patient had 2 psychiatric admissions that totaled 37 days. Although the patient’s presentation in the 2 previous admissions was similar to his presentation as described in Case 3, catatonia had not been identified or treated in either admission. Since his catatonia and mania were treated in Case 3, he has not required a readmission. The patient in Case 1 was previously hospitalized, but information about the LOS of these admissions was not available. These results suggest that early identification and treatment of catatonia via the approach we used can improve patient outcomes.

Bottom Line

Excited catatonia can be challenging to diagnose and treat because it can present with symptoms similar to those seen in mania or psychosis. We describe 3 cases in which we used a stepwise approach to optimize treatment and improve outcomes for patients with excited catatonia. This approach may work equally well for other catatonia subtypes.

Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: how to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Crouse EL, Joel B. Moran JB. Catatonia: recognition, management, and prevention of complications. Current Psychiatry. 2018;17(12):45-49.

Drug Brand Names

Clozapine • Clozaril
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Risperidone • Risperdal
Divalproex sodium • Depakote

Catatonia is often difficult to identify and treat. The excited catatonia subtype can be particularly challenging to diagnose because it can present with symptoms similar to those seen in mania or psychosis. In this article, we present 3 cases of excited catatonia that illustrate how to identify it, how to treat the catatonia as well as the underlying pathology, and factors to consider during this process to mitigate the risk of adverse outcomes. We also outline a treatment algorithm we used for the 3 cases. Although we describe using this approach for patients with excited catatonia, it is generalizable to other types of catatonia.

Many causes, varying presentations

Catatonia is a psychomotor syndrome characterized by mutism, negativism, stereotypy, waxy flexibility, and other symptoms.¹ It is defined by the presence of ≥3 of the 12 symptoms listed in the Table.² Causes of catatonia include metabolic abnormalities, endocrine disorders, drug intoxication, neurodevelopmental disorders, medication adverse effects, psychosis, and mood disorders.^1,3

A subtype of this syndrome, excited catatonia, can present with restlessness, agitation, emotional lability, poor sleep, and altered mental status in addition to the more typical symptoms.^1,4 Because excited catatonia can resemble mania or psychosis, it is particularly challenging to identify the underlying disorder causing it and appropriate treatment. Fink et al⁴ discussed how clinicians have interpreted the different presentations of excited catatonia to gain insight into the underlying diagnosis. If the patient’s thought process appears disorganized, psychosis may be suspected.⁴ If the patient is delusional and grandiose, they may be manic, and when altered mental status dominates the presentation, delirium may be the culprit.⁴

Regardless of the underlying cause, the first step is to treat the catatonia. Benzodiazepines and electroconvulsive therapy (ECT) are the most well validated treatments for catatonia and have been used to treat excited catatonia.¹ Excited catatonia is often misdiagnosed and subsequently mistreated. In the following 3 cases, excited catatonia was successfully identified and treated using the same approach (Figure).

Case 1

Mr. A, age 27, has a history of bipolar I disorder. He was brought to the hospital by ambulance after being found to be yelling and acting belligerently, and he was admitted to the inpatient psychiatry unit for manic decompensation due to medication nonadherence. He was started on divalproex sodium 500 mg twice a day for mood stabilization, risperidone 1 mg twice a day for adjunct mood stabilization and psychosis, and lorazepam 1 mg 3 times a day for agitation. Mr. A exhibited odd behavior; he would take off his clothes in the hallway, run around the unit, and randomly yell at staff or to himself. At other times, he would stay silent, repeat the same statements, or oddly posture in the hallway for minutes at a time. These behaviors were seen primarily in the hour or 2 preceding lorazepam administration and improved after he received lorazepam.

Mr. A’s treating team completed the Bush-Francis Catatonia Rating Scale (BFCRS), which yielded a positive catatonia screen of 7/14. As a result, divalproex sodium and risperidone were held, and lorazepam was increased to 2 mg twice a day.

After several days, Mr. A was no longer acting oddly and was able to speak more spontaneously; however, he began to exhibit overt signs of mania. He would speak rapidly and make grandiose claims about managing millions of dollars as the CEO of a famous company. Divalproex sodium was restarted at 500 mg twice a day and increased to 500 mg 3 times a day for mood stabilization. Mr. A continued to receive lorazepam 2 mg 3 times a day for catatonia, and risperidone was restarted at 1 mg twice a day to more effectively target his manic symptoms. Risperidone was increased to 2 mg twice a day. After this change, Mr. A’s grandiosity dissipated, his speech normalized, and his thought process became organized. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium 500 mg 3 times a day, and risperidone 2 mg twice a day. Mr. A’s length of stay (LOS) for this admission was 11 days.

Continue to: Case 2

Case 2

Mr. B, age 49, presented with irritability and odd posturing. He has a history of schizoaffective disorder, bipolar type for which he was receiving a maintenance regimen of lithium 600 mg/d at bedtime and risperidone 2 mg/d at bedtime. He had multiple previous psychiatric admissions for catatonia. On this admission, Mr. B was irritable and difficult to redirect. He yelled at staff members and had a stiff gait. The BFCRS yielded a positive screening score of 3/14 and a severity score of 8/23. As a result, the treatment team conducted a lorazepam challenge.

After Mr. B received lorazepam 1 mg IM, his thought organization and irritability improved, which allowed him to have a coherent conversation with the interviewer. His gait stiffness also improved. His risperidone and lithium were held, and oral lorazepam 1 mg 3 times a day was started for catatonia. Lorazepam was gradually increased to 4 mg 3 times a day. Mr. B became euthymic and redirectable, and had an improved gait. However, he was also tangential and hyperverbal; these symptoms were indicative of the underlying mania that precipitated his catatonia.

Divalproex sodium extended release (ER) was started and increased to 1,500 mg/d at bedtime for mood stabilization. Lithium was restarted and increased to 300 mg twice a day for adjunct mood stabilization. Risperidone was not restarted. Toward the end of his admission, Mr. B was noted to be overly sedated, so the lorazepam dosage was decreased. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium ER 1,500 mg/d at bedtime, and lithium 300 mg twice a day. At discharge, Mr. B was calm and euthymic, with a linear thought process. His LOS was 25 days.

Case 3

Mr. C, age 62, presented to the emergency department (ED) because he had exhibited erratic behavior and had not slept for the past week. He has a history of bipolar I disorder, hypothyroidism, diabetes, and hypertension. For many years, he had been stable on divalproex sodium ER 2,500 mg/d at bedtime for mood stabilization and clozapine 100 mg/d at bedtime for adjunct mood stabilization and psychosis. In the ED, Mr. C was irritable, distractible, and tangential. On admission, he was speaking slowly with increased speech latency in response to questions, exhibiting stereotypy, repeating statements over and over, and walking very slowly.

The BFCRS yielded a positive screening score of 5/14 and a severity score of 10/23. Lorazepam 1 mg IM was administered. After 15 minutes, Mr. C’s speech, gait, and distractibility improved. As a result, clozapine and divalproex sodium were held, and he was started on oral lorazepam 1 mg 3 times a day. After several days, Mr. C was speaking fluently and no longer exhibiting stereotypy or having outbursts where he would make repetitive statements. However, he was tangential and irritable at times, which were signs of his underlying mania. Divalproex sodium ER was restarted at 250 mg/d at bedtime for mood stabilization and gradually increased to 2,500 mg/d at bedtime. Clozapine was also restarted at 25 mg/d at bedtime and gradually increased to 200 mg/d at bedtime. The lorazepam was gradually tapered and discontinued over the course of 3 weeks due to oversedation.

Continue to: At discharge...

At discharge, Mr. C was euthymic, calm, linear, and goal-directed. He was discharged on divalproex sodium ER 2,500 mg/d at bedtime and clozapine 200 mg/d at bedtime. His LOS for this admission was 22 days.

A stepwise approach can improve outcomes

The Figure outlines the method we used to manage excited catatonia in these 3 cases. Each of these patients exhibited signs of excited catatonia, but because those symptoms were nearly identical to those of mania, it was initially difficult to identify catatonia. Excited catatonia was suspected after more typical catatonic symptoms—such as a stiff gait, slowed speech, and stereotypy—were observed. The BFCRS was completed to get an objective measure of the likelihood that the patient was catatonic. In all 3 cases, the BFCRS resulted in a positive screen for catatonia. Following this, the patients described in Case 2 and Case 3 received a lorazepam challenge, which confirmed their catatonia. No lorazepam challenge was performed in Case 1 because the patient was already receiving lorazepam when the BFCRS was completed. Although most catatonic patients will respond to a lorazepam challenge, not all will. Therefore, clinicians should maintain some degree of suspicion for catatonia if a patient has a positive screen on the BFCRS but a negative lorazepam challenge.

In all 3 cases, after catatonia was confirmed, the patient’s psychotropic medications were discontinued. In all 3 cases, the antipsychotic was held to prevent progression to neuroleptic malignant syndrome (NMS) or malignant catatonia. Rasmussen et al³ found that 3.6% of the catatonic patients in their sample who were treated with antipsychotics developed NMS. A review of prospective studies looking at patients treated with antipsychotics found the incidence of NMS was .07% to 1.8%.⁵ Because NMS is often clinically indistinguishable from malignant catatonia,^4,6 this incidence of NMS may have represented an increased incidence in malignant catatonia.

In all 3 cases, the mood stabilizer was held to prevent it from complicating the clinical picture. Discontinuing the mood stabilizer and focusing on treating the catatonia before targeting the underlying mania increased the likelihood of differentiating the patient’s catatonic symptoms from manic symptoms. This resulted in more precise medication selection and titration by allowing us to identify the specific symptoms that were being targeted by each medication.

Oral lorazepam was prescribed to target catatonia in all 3 cases, and the dosage was gradually increased until symptoms began to resolve. As the catatonia resolved, the manic symptoms became more easily identifiable, and at this point a mood stabilizer was started and titrated to a therapeutic dose to target the mania. In Case 1 and Case 3, the antipsychotic was restarted to treat the mania more effectively. It was not restarted in Case 2 because the patient’s mania was effectively being managed by 2 mood stabilizers. The risks and benefits of starting an antipsychotic in a catatonic or recently catatonic patient should be carefully considered. In the 2 cases where the antipsychotic was restarted, the patients were closely monitored, and there were no signs of NMS or malignant catatonia.

Continue to: As discharge approached...

As discharge approached, the dosages of oral lorazepam were reevaluated. Catatonic patients can typically tolerate high doses of benzodiazepines without becoming overly sedated, but each patient has a different threshold at which the dosage causes oversedation. In all 3 patients, lorazepam was initially titrated to a dose that treated their catatonic symptoms without causing intolerable sedation. In Case 2 and Case 3, as the catatonia began to resolve, the patients became increasingly sedated on their existing lorazepam dosage, so it was decreased. Because the patient in Case 1 did not become overly sedated, his lorazepam dosage did not need to be reduced.

For 2 of these patients, our approach resulted in a shorter LOS compared to their previous hospitalizations. The LOS in Case 2 was 25 days; 5 years earlier, he had a 49-day LOS for mania and catatonia. During the past admission, the identification and treatment of the catatonia was delayed, which resulted in the patient requiring multiple transfers to the medical unit for unstable vital signs. The LOS in Case 3 was 22 days; 6 months prior to this admission, the patient had 2 psychiatric admissions that totaled 37 days. Although the patient’s presentation in the 2 previous admissions was similar to his presentation as described in Case 3, catatonia had not been identified or treated in either admission. Since his catatonia and mania were treated in Case 3, he has not required a readmission. The patient in Case 1 was previously hospitalized, but information about the LOS of these admissions was not available. These results suggest that early identification and treatment of catatonia via the approach we used can improve patient outcomes.

Bottom Line

Excited catatonia can be challenging to diagnose and treat because it can present with symptoms similar to those seen in mania or psychosis. We describe 3 cases in which we used a stepwise approach to optimize treatment and improve outcomes for patients with excited catatonia. This approach may work equally well for other catatonia subtypes.

Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: how to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Crouse EL, Joel B. Moran JB. Catatonia: recognition, management, and prevention of complications. Current Psychiatry. 2018;17(12):45-49.

Drug Brand Names

Clozapine • Clozaril
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Risperidone • Risperdal
Divalproex sodium • Depakote

Catatonia is often difficult to identify and treat. The excited catatonia subtype can be particularly challenging to diagnose because it can present with symptoms similar to those seen in mania or psychosis. In this article, we present 3 cases of excited catatonia that illustrate how to identify it, how to treat the catatonia as well as the underlying pathology, and factors to consider during this process to mitigate the risk of adverse outcomes. We also outline a treatment algorithm we used for the 3 cases. Although we describe using this approach for patients with excited catatonia, it is generalizable to other types of catatonia.

Many causes, varying presentations

Catatonia is a psychomotor syndrome characterized by mutism, negativism, stereotypy, waxy flexibility, and other symptoms.¹ It is defined by the presence of ≥3 of the 12 symptoms listed in the Table.² Causes of catatonia include metabolic abnormalities, endocrine disorders, drug intoxication, neurodevelopmental disorders, medication adverse effects, psychosis, and mood disorders.^1,3

A subtype of this syndrome, excited catatonia, can present with restlessness, agitation, emotional lability, poor sleep, and altered mental status in addition to the more typical symptoms.^1,4 Because excited catatonia can resemble mania or psychosis, it is particularly challenging to identify the underlying disorder causing it and appropriate treatment. Fink et al⁴ discussed how clinicians have interpreted the different presentations of excited catatonia to gain insight into the underlying diagnosis. If the patient’s thought process appears disorganized, psychosis may be suspected.⁴ If the patient is delusional and grandiose, they may be manic, and when altered mental status dominates the presentation, delirium may be the culprit.⁴

Regardless of the underlying cause, the first step is to treat the catatonia. Benzodiazepines and electroconvulsive therapy (ECT) are the most well validated treatments for catatonia and have been used to treat excited catatonia.¹ Excited catatonia is often misdiagnosed and subsequently mistreated. In the following 3 cases, excited catatonia was successfully identified and treated using the same approach (Figure).

Case 1

Mr. A, age 27, has a history of bipolar I disorder. He was brought to the hospital by ambulance after being found to be yelling and acting belligerently, and he was admitted to the inpatient psychiatry unit for manic decompensation due to medication nonadherence. He was started on divalproex sodium 500 mg twice a day for mood stabilization, risperidone 1 mg twice a day for adjunct mood stabilization and psychosis, and lorazepam 1 mg 3 times a day for agitation. Mr. A exhibited odd behavior; he would take off his clothes in the hallway, run around the unit, and randomly yell at staff or to himself. At other times, he would stay silent, repeat the same statements, or oddly posture in the hallway for minutes at a time. These behaviors were seen primarily in the hour or 2 preceding lorazepam administration and improved after he received lorazepam.

Mr. A’s treating team completed the Bush-Francis Catatonia Rating Scale (BFCRS), which yielded a positive catatonia screen of 7/14. As a result, divalproex sodium and risperidone were held, and lorazepam was increased to 2 mg twice a day.

After several days, Mr. A was no longer acting oddly and was able to speak more spontaneously; however, he began to exhibit overt signs of mania. He would speak rapidly and make grandiose claims about managing millions of dollars as the CEO of a famous company. Divalproex sodium was restarted at 500 mg twice a day and increased to 500 mg 3 times a day for mood stabilization. Mr. A continued to receive lorazepam 2 mg 3 times a day for catatonia, and risperidone was restarted at 1 mg twice a day to more effectively target his manic symptoms. Risperidone was increased to 2 mg twice a day. After this change, Mr. A’s grandiosity dissipated, his speech normalized, and his thought process became organized. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium 500 mg 3 times a day, and risperidone 2 mg twice a day. Mr. A’s length of stay (LOS) for this admission was 11 days.

Continue to: Case 2

Case 2

Mr. B, age 49, presented with irritability and odd posturing. He has a history of schizoaffective disorder, bipolar type for which he was receiving a maintenance regimen of lithium 600 mg/d at bedtime and risperidone 2 mg/d at bedtime. He had multiple previous psychiatric admissions for catatonia. On this admission, Mr. B was irritable and difficult to redirect. He yelled at staff members and had a stiff gait. The BFCRS yielded a positive screening score of 3/14 and a severity score of 8/23. As a result, the treatment team conducted a lorazepam challenge.

After Mr. B received lorazepam 1 mg IM, his thought organization and irritability improved, which allowed him to have a coherent conversation with the interviewer. His gait stiffness also improved. His risperidone and lithium were held, and oral lorazepam 1 mg 3 times a day was started for catatonia. Lorazepam was gradually increased to 4 mg 3 times a day. Mr. B became euthymic and redirectable, and had an improved gait. However, he was also tangential and hyperverbal; these symptoms were indicative of the underlying mania that precipitated his catatonia.

Divalproex sodium extended release (ER) was started and increased to 1,500 mg/d at bedtime for mood stabilization. Lithium was restarted and increased to 300 mg twice a day for adjunct mood stabilization. Risperidone was not restarted. Toward the end of his admission, Mr. B was noted to be overly sedated, so the lorazepam dosage was decreased. He was discharged on lorazepam 2 mg 3 times a day, divalproex sodium ER 1,500 mg/d at bedtime, and lithium 300 mg twice a day. At discharge, Mr. B was calm and euthymic, with a linear thought process. His LOS was 25 days.

Case 3

Mr. C, age 62, presented to the emergency department (ED) because he had exhibited erratic behavior and had not slept for the past week. He has a history of bipolar I disorder, hypothyroidism, diabetes, and hypertension. For many years, he had been stable on divalproex sodium ER 2,500 mg/d at bedtime for mood stabilization and clozapine 100 mg/d at bedtime for adjunct mood stabilization and psychosis. In the ED, Mr. C was irritable, distractible, and tangential. On admission, he was speaking slowly with increased speech latency in response to questions, exhibiting stereotypy, repeating statements over and over, and walking very slowly.

The BFCRS yielded a positive screening score of 5/14 and a severity score of 10/23. Lorazepam 1 mg IM was administered. After 15 minutes, Mr. C’s speech, gait, and distractibility improved. As a result, clozapine and divalproex sodium were held, and he was started on oral lorazepam 1 mg 3 times a day. After several days, Mr. C was speaking fluently and no longer exhibiting stereotypy or having outbursts where he would make repetitive statements. However, he was tangential and irritable at times, which were signs of his underlying mania. Divalproex sodium ER was restarted at 250 mg/d at bedtime for mood stabilization and gradually increased to 2,500 mg/d at bedtime. Clozapine was also restarted at 25 mg/d at bedtime and gradually increased to 200 mg/d at bedtime. The lorazepam was gradually tapered and discontinued over the course of 3 weeks due to oversedation.

Continue to: At discharge...

At discharge, Mr. C was euthymic, calm, linear, and goal-directed. He was discharged on divalproex sodium ER 2,500 mg/d at bedtime and clozapine 200 mg/d at bedtime. His LOS for this admission was 22 days.

A stepwise approach can improve outcomes

The Figure outlines the method we used to manage excited catatonia in these 3 cases. Each of these patients exhibited signs of excited catatonia, but because those symptoms were nearly identical to those of mania, it was initially difficult to identify catatonia. Excited catatonia was suspected after more typical catatonic symptoms—such as a stiff gait, slowed speech, and stereotypy—were observed. The BFCRS was completed to get an objective measure of the likelihood that the patient was catatonic. In all 3 cases, the BFCRS resulted in a positive screen for catatonia. Following this, the patients described in Case 2 and Case 3 received a lorazepam challenge, which confirmed their catatonia. No lorazepam challenge was performed in Case 1 because the patient was already receiving lorazepam when the BFCRS was completed. Although most catatonic patients will respond to a lorazepam challenge, not all will. Therefore, clinicians should maintain some degree of suspicion for catatonia if a patient has a positive screen on the BFCRS but a negative lorazepam challenge.

In all 3 cases, after catatonia was confirmed, the patient’s psychotropic medications were discontinued. In all 3 cases, the antipsychotic was held to prevent progression to neuroleptic malignant syndrome (NMS) or malignant catatonia. Rasmussen et al³ found that 3.6% of the catatonic patients in their sample who were treated with antipsychotics developed NMS. A review of prospective studies looking at patients treated with antipsychotics found the incidence of NMS was .07% to 1.8%.⁵ Because NMS is often clinically indistinguishable from malignant catatonia,^4,6 this incidence of NMS may have represented an increased incidence in malignant catatonia.

In all 3 cases, the mood stabilizer was held to prevent it from complicating the clinical picture. Discontinuing the mood stabilizer and focusing on treating the catatonia before targeting the underlying mania increased the likelihood of differentiating the patient’s catatonic symptoms from manic symptoms. This resulted in more precise medication selection and titration by allowing us to identify the specific symptoms that were being targeted by each medication.

Oral lorazepam was prescribed to target catatonia in all 3 cases, and the dosage was gradually increased until symptoms began to resolve. As the catatonia resolved, the manic symptoms became more easily identifiable, and at this point a mood stabilizer was started and titrated to a therapeutic dose to target the mania. In Case 1 and Case 3, the antipsychotic was restarted to treat the mania more effectively. It was not restarted in Case 2 because the patient’s mania was effectively being managed by 2 mood stabilizers. The risks and benefits of starting an antipsychotic in a catatonic or recently catatonic patient should be carefully considered. In the 2 cases where the antipsychotic was restarted, the patients were closely monitored, and there were no signs of NMS or malignant catatonia.

Continue to: As discharge approached...

As discharge approached, the dosages of oral lorazepam were reevaluated. Catatonic patients can typically tolerate high doses of benzodiazepines without becoming overly sedated, but each patient has a different threshold at which the dosage causes oversedation. In all 3 patients, lorazepam was initially titrated to a dose that treated their catatonic symptoms without causing intolerable sedation. In Case 2 and Case 3, as the catatonia began to resolve, the patients became increasingly sedated on their existing lorazepam dosage, so it was decreased. Because the patient in Case 1 did not become overly sedated, his lorazepam dosage did not need to be reduced.

For 2 of these patients, our approach resulted in a shorter LOS compared to their previous hospitalizations. The LOS in Case 2 was 25 days; 5 years earlier, he had a 49-day LOS for mania and catatonia. During the past admission, the identification and treatment of the catatonia was delayed, which resulted in the patient requiring multiple transfers to the medical unit for unstable vital signs. The LOS in Case 3 was 22 days; 6 months prior to this admission, the patient had 2 psychiatric admissions that totaled 37 days. Although the patient’s presentation in the 2 previous admissions was similar to his presentation as described in Case 3, catatonia had not been identified or treated in either admission. Since his catatonia and mania were treated in Case 3, he has not required a readmission. The patient in Case 1 was previously hospitalized, but information about the LOS of these admissions was not available. These results suggest that early identification and treatment of catatonia via the approach we used can improve patient outcomes.

Bottom Line

Excited catatonia can be challenging to diagnose and treat because it can present with symptoms similar to those seen in mania or psychosis. We describe 3 cases in which we used a stepwise approach to optimize treatment and improve outcomes for patients with excited catatonia. This approach may work equally well for other catatonia subtypes.

Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: how to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Crouse EL, Joel B. Moran JB. Catatonia: recognition, management, and prevention of complications. Current Psychiatry. 2018;17(12):45-49.

Drug Brand Names

Clozapine • Clozaril
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Risperidone • Risperdal
Divalproex sodium • Depakote

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

The homicide rate among children in the United States rose by more than 4% per year since 2013 but jumped nearly 28% from 2019 to 2020, new data show.

Although long-term trends varied by region and demographics, with some groups and areas seeing declines in killings, the increases were the highest among Black children and boys aged 11-17, according to the researchers, who attribute the surge in violent deaths to a recent rise in firearm-related killings in children. Gun violence is now the leading cause of death for children in the United States, claiming what the American Academy of Pediatrics has equated to a classroomful of lives each day.

“There are troubling recent rate increases among several groups, warranting immediate attention, with some racial and ethnic disparities persisting for more than 20 years,” said Rebecca F. Wilson, PhD, of the U.S. Centers for Disease Control and Prevention, who helped conduct the study.

Dr. Wilson and her colleagues, whose findings appear in JAMA Pediatrics, examined data on 38,362 homicide victims in the United States aged 0-17 years who were killed between 1999 and 2020.

The nation’s overall homicide rate for youth fell by 5.6% per year from 2007 to 2013 before reversing course. Between 2013 and 2020, the overall rate rose 4.3% annually.

The figures show that not all children are affected equally. The rate of child homicide has fallen significantly for girls, infants, and children ages 5 years and under – whose deaths often result from caregiver neglect or violence – as well as Asian or Pacific Islanders, Whites, and those living in the Northeast.

But the child homicide rate in the South increased 6.4% per year between 2013 and 2020, while that of children in both rural America and in cities is also rising after years of decline, according to the researchers.

The suspected perpetrator was known in about 64% of child killings. Nearly 80% of those perpetrators were male.

Dr. Wilson and her colleagues also note that the COVID-19 pandemic appears to have precipitated a wave of gun-related violence among children – a link borne out by another recent paper in JAMA Pediatrics. (Recent data suggest that intentional firearm injuries are often misclassified as accidental.)

The study found that gun-related injuries in youth remained elevated through 2021, with non-Hispanic Black children and those with public insurance making up greater proportions of victims during the pandemic. The researchers identified 1,815 firearm injuries per month before the pandemic and 2,759 per month during the outbreak, a 52% increase.

Although the two studies look at different data, both show that Black children are most affected by gun violence, experts said.

“This demonstrates a critical issue for the medical, public health, and legal communities: While homicide is often presented as a criminal justice problem, it is increasingly a racial justice problem,” said Katherine E. Hoops, MD, of the Center for Gun Violence Solutions at Johns Hopkins Bloomberg School of Public Health, Baltimore.

In an editorial about the homicide study, researchers at the University of Pennsylvania, Philadelphia, called the violent deaths “preventable and unacceptable.” Eliminating such deaths “must be among our first priorities,” they wrote.

The editorial authors also noted that researchers know relatively little about nonfatal violent injuries such as those involving firearms. “These injuries are important not only because they may have life-altering consequences for children and families but also because understanding only the most severe form of any health condition (death) will hamper our ability to design and evaluate prevention strategies,” they wrote.

Dr. Wilson’s group identified different causes of youth homicide for different age groups – and the potential interventions for each differ. Although the youngest children are more likely to die from abuse or neglect, those aged 6-10 years were most likely to die by firearm, often associated with abuse that ends in suicide. Meanwhile, adolescents aged 11-17 were more subject to peer violence.

For Dr. Hoops, “each of these differences has important policy implications, including the need for policies that address structural racism, poverty, and systematic disadvantage – but also firearm safe storage to prevent youth violence and suicide [and] reduction of access to lethal means, such as through extreme risk protective orders when someone is at risk of harming themselves or others.”

Dr. Wilson agreed. “We know child homicides are preventable,” she said. “The rate decrease for some groups is encouraging, yet more can be done to protect all children.”

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

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

Sleep-disordered breathing was significantly associated with increased odds of preeclampsia and with greater arterial stiffness in high-risk pregnancies, based on data from 181 individuals.

The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.

SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m² or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.

Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.

Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.

Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.

The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.

The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.

However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.

“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.

The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.

Sleep-disordered breathing was significantly associated with increased odds of preeclampsia and with greater arterial stiffness in high-risk pregnancies, based on data from 181 individuals.

The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.

SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m² or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.

Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.

Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.

Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.

The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.

The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.

However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.

“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.

The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.

Sleep-disordered breathing was significantly associated with increased odds of preeclampsia and with greater arterial stiffness in high-risk pregnancies, based on data from 181 individuals.

The intermittent hypoxia resulting from sleep-disordered breathing (SDB) has been linked to cardiovascular disease and hypertension, wrote Kim Phan, PhD, of McGill University, Montreal, and colleagues.

SDB has been associated with increased preeclampsia risk, and women with preeclampsia show increased arterial stiffness, but an association between SDB and arterial stiffness in pregnancy has not been explored, they said.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 181 women with high-risk singleton pregnancies recruited from two tertiary obstetrics clinics in Montreal. High-risk pregnancy was defined as meeting at least one of the following criteria: age 35 years and older, body mass index 25 kg/m² or higher, chronic hypertension, preexisting diabetes mellitus, preexisting renal disease, or personal or first-degree relative with a history of preeclampsia.

Participants were assessed at each trimester via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaire. Sleep-disordered breathing was defined as loud snoring or witnessed sleep apneas at least three times a week. Arterial stiffness was assessed via applanation tonometry every 4 weeks from baseline throughout pregnancy.

Overall, 23% of the study population met the criteria for SDB; SDB in the first or second trimester was associated with a significantly increased risk of preeclampsia (odds ratio 3.4). The effect of SDB on preeclampsia was increased in women who reported excessive daytime sleepiness, defined as scores higher than 10 on the Epworth Sleepiness Scale. The odds ratio for preeclampsia in the first or second trimester increased to 5.7 in women with hypersomnolence in addition to SDB. The risk of preeclampsia was even higher (OR 8.2) in the third trimester.

Self-reported total sleep time decreased in the second and third trimesters compared with the first, but reports of excessive daytime sleepiness remained consistent throughout the pregnancies, the researchers noted.

The results highlight the need to screen pregnant women for SDB in all three trimesters; however, “future studies will need to assess the incremental benefit of integrating SDB into risk assessment calculators in pregnancy,” the researchers wrote in their discussion. Randomized trials are needed to determine the value of interventions such as continuous positive airway pressure to reduce arterial stiffness and the risks of hypertensive disorders of pregnancy, they said. More data also are needed to examine the role of excessive daytime sleepiness as a modifier of arterial stiffness and preeclampsia risk, they noted.

The findings were limited by the prospective design, which prevents conclusions of causality, the researchers noted. Other limitations included the focus on high-risk pregnancy, which may limit generalizability, and the use of symptoms, not sleep recordings, to identify SDB, they said.

However, the results show an independent association between SDB and arterial stiffness during pregnancy, and offer potentially useful insights into the mechanisms of SDB-associated cardiovascular conditions, they noted.

“This work may inform future studies exploring the value of using arterial stiffness, as an early noninvasive indicator of subclinical vascular dysfunction in pregnant women with SDB,” they concluded.

The study was supported by the Fonds de recherche du Quebec – Sante (FRQS), Heart and Stroke Foundation of Canada, McGill University’s academic enrichment fund, and the Canadian Foundation for Women’s Health. The researchers had no financial conflicts to disclose.

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

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

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

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

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.

Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. We are currently facing what many are calling a “tripledemic” as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.

During the first week of December, cases of influenza were rising across the country¹ and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
 

Influenza

Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.

RSV

In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.²

COVID-19

Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.

There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.

If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.³

With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.

Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
 

In summary

Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.

2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.

3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.

This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.

Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. We are currently facing what many are calling a “tripledemic” as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.

During the first week of December, cases of influenza were rising across the country¹ and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
 

Influenza

Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.

RSV

In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.²

COVID-19

Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.

There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.

If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.³

With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.

Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
 

In summary

Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.

2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.

3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.

This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.

Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. We are currently facing what many are calling a “tripledemic” as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.

During the first week of December, cases of influenza were rising across the country¹ and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
 

Influenza

Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.

RSV

In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.²

COVID-19

Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.

There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.

If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.³

With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.

Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
 

In summary

Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.

2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.

3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.