Mental Health

Children with attention-deficit/hyperactivity disorder (ADHD) are mainly cared for in primary care settings by us. Management of this chronic neurodevelopmental condition that affects 5+% of children worldwide should include proper diagnosis, assessment for contributing and comorbid conditions, behavioral intervention (the primary treatment for preschoolers), ensuring good sleep and nutrition, and usually medication.

Because stimulants are very effective for reducing ADHD symptoms, we may readily begin these first-line medications even on the initial visit when the diagnosis is determined. But are we really thoughtful about knowing and explaining the potential short- and long-term side effects of these medications that may then be used for many years? Considerable discussion with the child and parents may be needed to address their concerns, balanced with benefits, and to make a plan for their access and use of stimulants (and other medications for ADHD not the topic here).

Consider the Side Effects

In children older than 6 years, some form of either a methylphenidate (MPH) or a dextroamphetamine (DA) class of stimulant have been shown to be equally effective in reducing symptoms of ADHD in about 77% of cases, but side effects are common, mostly mild, and mostly in the first months of use. These include reduced appetite, abdominal pain, headache, weight loss, tics, jitteriness, and delays in falling asleep. About half of all children treated will have one of these adverse effects over 5 years, with reduced appetite the most common. There is no difference in effectiveness or side effects by presentation type, i.e. hyperactive, inattentive, or combined, but the DA forms are associated with more side effects than MPH (10% vs. 6%). Medicated preschoolers have more and different side effects which, in addition to those above, may include listlessness, social withdrawal, and repetitive movements. Fortunately, we can reassure families that side effects can usually be readily managed by slower ramp up of dose, spacing to ensure appetite for meals, extra snacks, attention to bowel patterns and bedtime routines, or change in medication class.

Rates of tics while on stimulants are low irrespective of whether DA or MPH is used, and are usually transient, but difficult cases may occur, sometimes as part of Tourette’s, although not a contraindication. Additional side effects of concern are anxiety, irritability, sadness, and overfocusing that may require a change in class of stimulant or to a nonstimulant. Keep in mind that these symptoms may represent comorbid conditions to ADHD, warranting counseling intervention rather than being a medication side effect. Both initial assessment for ADHD and monitoring should look for comorbidities whether medication is used or not.

Measuring height, weight, pulse, and blood pressure should be part of ADHD care. How concerned should you and the family be about variations? Growth rate declines are more common in preschool children; in the PATS study height varied by 20.3%, and weight by 55.2%, more in heavier children. Growth can be protected by providing favored food for school, encouraging eating when hungry, and an evening fourth meal. You can reassure families that, even with continual use of stimulant medicines for years and initial deficits of 2 cm and 2.7 kg compared to expected, no significant differences remain in adulthood.

This longitudinal growth data was collected when short-acting stimulants were the usual, rather than the now common long-acting stimulants given 7 days per week, however. Children on transdermal MPH with 12-hour release over 3 years showed a small but significant delay in growth with the mean deficit rates 1.3 kg/year mainly in the first year, and 0.68 cm/year in height in the second year. If we see growth not recovering as it is expected to after the first year of treatment, we can advise shorter-acting forms, and medication “holidays” on weekends or vacations, that reduce but do not end the deficits. When concerned, a nonstimulant can be selected.

Blood pressure and pulse rate are predictably slightly increased on stimulants (about 2-4 mm Hg and about 3-6 bpm) but not clinically significantly. Although ECGs are not routinely recommended, careful consideration and consultation is warranted before starting stimulants for any patient with structural cardiac abnormalities, unexplained syncope, exertional chest pain, or a family history of sudden death in children or young adults. Neither current nor former users of stimulants for ADHD were found to have greater rates of cardiac events than the general population, however.
 

Misuse and abuse

Misuse and diversion of stimulants is common (e.g. 26% diverted MPH in the past month; 14% of 12th graders divert DA), often undetected, and potentially dangerous. And the problem is not limited to just the kids. Sixteen percent of parents reported diversion of stimulant medication to another household member, mainly to themselves. Stimulant overdose can occur, especially taken parenterally, and presents with dilated pupils, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and/or seizures. Fortunately, overdose of prescribed stimulants is rarely fatal if medically managed, but recent “fake” Adderall (not from pharmacies) has been circulating. These fake drugs may contain lethal amounts of fentanyl or methamphetamine. Point out to families that a peer-provided stimulant not prescribed for them may have underlying medical or psychiatric issues that increase adverse events. Selling stimulants can have serious legal implications, with punishments ranging from fines to incarceration. A record of arrest during adolescence increases the likelihood of high school dropout, lack of 4-year college education, and later employment barriers. Besides these serious outcomes, it is useful to remind patients that if they deviate from your recommended dosing that you, and others, will not prescribe for them in the future the medication that has been supporting their successful functioning.

You can be fooled about being able to tell if your patients are misusing or diverting the stimulants you prescribe. Most (59%) physicians suspect that more than one of their patients with ADHD has diverted or feigned symptoms (66%) to get a prescription. Women were less likely to suspect their patients than are men, though, so be vigilant! Child psychiatrists had the highest suspicion with their greater proportion of patients with ADHD plus conduct or substance use disorder, who account for 83% of misusers/diverters. We can use education about misuse, pill counts, contracts on dosing, or switching to long-acting or nonstimulants to curb this.
 

Additional concerns

With more ADHD diagnosis and stimulants used for many years should we worry about longer-term issues? There have been reports in rodent models and a few children of chromosomal changes with stimulant exposure, but reviewers do not interpret these as an individual cancer risk. Record review of patients who received stimulants showed lower numbers of cancer than expected. Nor is there evidence of reproductive effects of stimulants, although use during pregnancy is not cleared.

Stimulants carry a boxed warning as having high potential for abuse and psychological or physical dependence, which is unsurprising given their effects on brain reward pathways. However, neither past nor present use of stimulants for ADHD has been associated with greater substance use long term.

To top off these issues, recent shortages of stimulants complicate ADHD management. Most states require electronic prescribing, US rules only allowing one transfer of such e-prescriptions. With many pharmacies refusing to tell families about availability, we must make multiple calls to locate a source. Pharmacists could help us by looking up patient names of abusers on the registry and identifying sites with adequate supplies.

While we need to educate ourselves and our patients about potential and manifest side effects and risks of stimulants, we need to balance those concerns with their high effectiveness for improving daily functioning of our many patients with ADHD.

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Children with attention-deficit/hyperactivity disorder (ADHD) are mainly cared for in primary care settings by us. Management of this chronic neurodevelopmental condition that affects 5+% of children worldwide should include proper diagnosis, assessment for contributing and comorbid conditions, behavioral intervention (the primary treatment for preschoolers), ensuring good sleep and nutrition, and usually medication.

Because stimulants are very effective for reducing ADHD symptoms, we may readily begin these first-line medications even on the initial visit when the diagnosis is determined. But are we really thoughtful about knowing and explaining the potential short- and long-term side effects of these medications that may then be used for many years? Considerable discussion with the child and parents may be needed to address their concerns, balanced with benefits, and to make a plan for their access and use of stimulants (and other medications for ADHD not the topic here).

Consider the Side Effects

In children older than 6 years, some form of either a methylphenidate (MPH) or a dextroamphetamine (DA) class of stimulant have been shown to be equally effective in reducing symptoms of ADHD in about 77% of cases, but side effects are common, mostly mild, and mostly in the first months of use. These include reduced appetite, abdominal pain, headache, weight loss, tics, jitteriness, and delays in falling asleep. About half of all children treated will have one of these adverse effects over 5 years, with reduced appetite the most common. There is no difference in effectiveness or side effects by presentation type, i.e. hyperactive, inattentive, or combined, but the DA forms are associated with more side effects than MPH (10% vs. 6%). Medicated preschoolers have more and different side effects which, in addition to those above, may include listlessness, social withdrawal, and repetitive movements. Fortunately, we can reassure families that side effects can usually be readily managed by slower ramp up of dose, spacing to ensure appetite for meals, extra snacks, attention to bowel patterns and bedtime routines, or change in medication class.

Rates of tics while on stimulants are low irrespective of whether DA or MPH is used, and are usually transient, but difficult cases may occur, sometimes as part of Tourette’s, although not a contraindication. Additional side effects of concern are anxiety, irritability, sadness, and overfocusing that may require a change in class of stimulant or to a nonstimulant. Keep in mind that these symptoms may represent comorbid conditions to ADHD, warranting counseling intervention rather than being a medication side effect. Both initial assessment for ADHD and monitoring should look for comorbidities whether medication is used or not.

Measuring height, weight, pulse, and blood pressure should be part of ADHD care. How concerned should you and the family be about variations? Growth rate declines are more common in preschool children; in the PATS study height varied by 20.3%, and weight by 55.2%, more in heavier children. Growth can be protected by providing favored food for school, encouraging eating when hungry, and an evening fourth meal. You can reassure families that, even with continual use of stimulant medicines for years and initial deficits of 2 cm and 2.7 kg compared to expected, no significant differences remain in adulthood.

This longitudinal growth data was collected when short-acting stimulants were the usual, rather than the now common long-acting stimulants given 7 days per week, however. Children on transdermal MPH with 12-hour release over 3 years showed a small but significant delay in growth with the mean deficit rates 1.3 kg/year mainly in the first year, and 0.68 cm/year in height in the second year. If we see growth not recovering as it is expected to after the first year of treatment, we can advise shorter-acting forms, and medication “holidays” on weekends or vacations, that reduce but do not end the deficits. When concerned, a nonstimulant can be selected.

Blood pressure and pulse rate are predictably slightly increased on stimulants (about 2-4 mm Hg and about 3-6 bpm) but not clinically significantly. Although ECGs are not routinely recommended, careful consideration and consultation is warranted before starting stimulants for any patient with structural cardiac abnormalities, unexplained syncope, exertional chest pain, or a family history of sudden death in children or young adults. Neither current nor former users of stimulants for ADHD were found to have greater rates of cardiac events than the general population, however.
 

Misuse and abuse

Misuse and diversion of stimulants is common (e.g. 26% diverted MPH in the past month; 14% of 12th graders divert DA), often undetected, and potentially dangerous. And the problem is not limited to just the kids. Sixteen percent of parents reported diversion of stimulant medication to another household member, mainly to themselves. Stimulant overdose can occur, especially taken parenterally, and presents with dilated pupils, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and/or seizures. Fortunately, overdose of prescribed stimulants is rarely fatal if medically managed, but recent “fake” Adderall (not from pharmacies) has been circulating. These fake drugs may contain lethal amounts of fentanyl or methamphetamine. Point out to families that a peer-provided stimulant not prescribed for them may have underlying medical or psychiatric issues that increase adverse events. Selling stimulants can have serious legal implications, with punishments ranging from fines to incarceration. A record of arrest during adolescence increases the likelihood of high school dropout, lack of 4-year college education, and later employment barriers. Besides these serious outcomes, it is useful to remind patients that if they deviate from your recommended dosing that you, and others, will not prescribe for them in the future the medication that has been supporting their successful functioning.

You can be fooled about being able to tell if your patients are misusing or diverting the stimulants you prescribe. Most (59%) physicians suspect that more than one of their patients with ADHD has diverted or feigned symptoms (66%) to get a prescription. Women were less likely to suspect their patients than are men, though, so be vigilant! Child psychiatrists had the highest suspicion with their greater proportion of patients with ADHD plus conduct or substance use disorder, who account for 83% of misusers/diverters. We can use education about misuse, pill counts, contracts on dosing, or switching to long-acting or nonstimulants to curb this.
 

Additional concerns

With more ADHD diagnosis and stimulants used for many years should we worry about longer-term issues? There have been reports in rodent models and a few children of chromosomal changes with stimulant exposure, but reviewers do not interpret these as an individual cancer risk. Record review of patients who received stimulants showed lower numbers of cancer than expected. Nor is there evidence of reproductive effects of stimulants, although use during pregnancy is not cleared.

Stimulants carry a boxed warning as having high potential for abuse and psychological or physical dependence, which is unsurprising given their effects on brain reward pathways. However, neither past nor present use of stimulants for ADHD has been associated with greater substance use long term.

To top off these issues, recent shortages of stimulants complicate ADHD management. Most states require electronic prescribing, US rules only allowing one transfer of such e-prescriptions. With many pharmacies refusing to tell families about availability, we must make multiple calls to locate a source. Pharmacists could help us by looking up patient names of abusers on the registry and identifying sites with adequate supplies.

While we need to educate ourselves and our patients about potential and manifest side effects and risks of stimulants, we need to balance those concerns with their high effectiveness for improving daily functioning of our many patients with ADHD.

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Children with attention-deficit/hyperactivity disorder (ADHD) are mainly cared for in primary care settings by us. Management of this chronic neurodevelopmental condition that affects 5+% of children worldwide should include proper diagnosis, assessment for contributing and comorbid conditions, behavioral intervention (the primary treatment for preschoolers), ensuring good sleep and nutrition, and usually medication.

Because stimulants are very effective for reducing ADHD symptoms, we may readily begin these first-line medications even on the initial visit when the diagnosis is determined. But are we really thoughtful about knowing and explaining the potential short- and long-term side effects of these medications that may then be used for many years? Considerable discussion with the child and parents may be needed to address their concerns, balanced with benefits, and to make a plan for their access and use of stimulants (and other medications for ADHD not the topic here).

Consider the Side Effects

In children older than 6 years, some form of either a methylphenidate (MPH) or a dextroamphetamine (DA) class of stimulant have been shown to be equally effective in reducing symptoms of ADHD in about 77% of cases, but side effects are common, mostly mild, and mostly in the first months of use. These include reduced appetite, abdominal pain, headache, weight loss, tics, jitteriness, and delays in falling asleep. About half of all children treated will have one of these adverse effects over 5 years, with reduced appetite the most common. There is no difference in effectiveness or side effects by presentation type, i.e. hyperactive, inattentive, or combined, but the DA forms are associated with more side effects than MPH (10% vs. 6%). Medicated preschoolers have more and different side effects which, in addition to those above, may include listlessness, social withdrawal, and repetitive movements. Fortunately, we can reassure families that side effects can usually be readily managed by slower ramp up of dose, spacing to ensure appetite for meals, extra snacks, attention to bowel patterns and bedtime routines, or change in medication class.

Rates of tics while on stimulants are low irrespective of whether DA or MPH is used, and are usually transient, but difficult cases may occur, sometimes as part of Tourette’s, although not a contraindication. Additional side effects of concern are anxiety, irritability, sadness, and overfocusing that may require a change in class of stimulant or to a nonstimulant. Keep in mind that these symptoms may represent comorbid conditions to ADHD, warranting counseling intervention rather than being a medication side effect. Both initial assessment for ADHD and monitoring should look for comorbidities whether medication is used or not.

Measuring height, weight, pulse, and blood pressure should be part of ADHD care. How concerned should you and the family be about variations? Growth rate declines are more common in preschool children; in the PATS study height varied by 20.3%, and weight by 55.2%, more in heavier children. Growth can be protected by providing favored food for school, encouraging eating when hungry, and an evening fourth meal. You can reassure families that, even with continual use of stimulant medicines for years and initial deficits of 2 cm and 2.7 kg compared to expected, no significant differences remain in adulthood.

This longitudinal growth data was collected when short-acting stimulants were the usual, rather than the now common long-acting stimulants given 7 days per week, however. Children on transdermal MPH with 12-hour release over 3 years showed a small but significant delay in growth with the mean deficit rates 1.3 kg/year mainly in the first year, and 0.68 cm/year in height in the second year. If we see growth not recovering as it is expected to after the first year of treatment, we can advise shorter-acting forms, and medication “holidays” on weekends or vacations, that reduce but do not end the deficits. When concerned, a nonstimulant can be selected.

Blood pressure and pulse rate are predictably slightly increased on stimulants (about 2-4 mm Hg and about 3-6 bpm) but not clinically significantly. Although ECGs are not routinely recommended, careful consideration and consultation is warranted before starting stimulants for any patient with structural cardiac abnormalities, unexplained syncope, exertional chest pain, or a family history of sudden death in children or young adults. Neither current nor former users of stimulants for ADHD were found to have greater rates of cardiac events than the general population, however.
 

Misuse and abuse

Misuse and diversion of stimulants is common (e.g. 26% diverted MPH in the past month; 14% of 12th graders divert DA), often undetected, and potentially dangerous. And the problem is not limited to just the kids. Sixteen percent of parents reported diversion of stimulant medication to another household member, mainly to themselves. Stimulant overdose can occur, especially taken parenterally, and presents with dilated pupils, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and/or seizures. Fortunately, overdose of prescribed stimulants is rarely fatal if medically managed, but recent “fake” Adderall (not from pharmacies) has been circulating. These fake drugs may contain lethal amounts of fentanyl or methamphetamine. Point out to families that a peer-provided stimulant not prescribed for them may have underlying medical or psychiatric issues that increase adverse events. Selling stimulants can have serious legal implications, with punishments ranging from fines to incarceration. A record of arrest during adolescence increases the likelihood of high school dropout, lack of 4-year college education, and later employment barriers. Besides these serious outcomes, it is useful to remind patients that if they deviate from your recommended dosing that you, and others, will not prescribe for them in the future the medication that has been supporting their successful functioning.

You can be fooled about being able to tell if your patients are misusing or diverting the stimulants you prescribe. Most (59%) physicians suspect that more than one of their patients with ADHD has diverted or feigned symptoms (66%) to get a prescription. Women were less likely to suspect their patients than are men, though, so be vigilant! Child psychiatrists had the highest suspicion with their greater proportion of patients with ADHD plus conduct or substance use disorder, who account for 83% of misusers/diverters. We can use education about misuse, pill counts, contracts on dosing, or switching to long-acting or nonstimulants to curb this.
 

Additional concerns

With more ADHD diagnosis and stimulants used for many years should we worry about longer-term issues? There have been reports in rodent models and a few children of chromosomal changes with stimulant exposure, but reviewers do not interpret these as an individual cancer risk. Record review of patients who received stimulants showed lower numbers of cancer than expected. Nor is there evidence of reproductive effects of stimulants, although use during pregnancy is not cleared.

Stimulants carry a boxed warning as having high potential for abuse and psychological or physical dependence, which is unsurprising given their effects on brain reward pathways. However, neither past nor present use of stimulants for ADHD has been associated with greater substance use long term.

To top off these issues, recent shortages of stimulants complicate ADHD management. Most states require electronic prescribing, US rules only allowing one transfer of such e-prescriptions. With many pharmacies refusing to tell families about availability, we must make multiple calls to locate a source. Pharmacists could help us by looking up patient names of abusers on the registry and identifying sites with adequate supplies.

While we need to educate ourselves and our patients about potential and manifest side effects and risks of stimulants, we need to balance those concerns with their high effectiveness for improving daily functioning of our many patients with ADHD.

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients receiving long-acting injectable (LAI) antipsychotics upon hospital discharge were 75% less likely to be readmitted 30 days later compared with those who received an oral antipsychotic, new research showed.

Investigators reported the findings support the use of LAI antipsychotics over oral medication following a hospital stay for schizophrenia or schizoaffective disorder.

“I suspect the lower readmission rate that has been observed with long-acting injections has more to do with people forgetting to take a pill each and every day than with any inherent superiority of the injectable medication,” lead author Daniel Greer, PharmD, BCPP, clinical assistant professor at Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, said in a news release.

“Other studies on the use of antipsychotic medication have found that roughly three fourths of patients do not take oral medications exactly as directed, and it’s much easier to get a shot every few months than it is to take a pill every day, even though the shot requires a trip to the doctor,” Dr. Greer added.

The study was published online on January 17, 2024, in the Journal of Clinical Psychopharmacology.
 

Fewer Repeat Stays

Investigators compared 30-day readmission rates for all 343 patients with schizophrenia or schizoaffective disorder who were discharged from an inpatient psychiatric unit between August 2019 and June 2022.

A total of 240 patients (70%) were discharged on an oral antipsychotic, most commonly risperidone or olanzapine, and 103 (30%) were sent home on an LAI antipsychotic, most commonly aripiprazole lauroxil or haloperidol decanoate.

Within 30 days of discharge, 22 patients (6.4%) were readmitted for a schizophrenic or schizoaffective exacerbation — two in the LAI antipsychotic group and 20 in the oral antipsychotic group (1.9% vs 8.3%; P = .03).

The LAI antipsychotic group had a higher average daily chlorpromazine equivalent antipsychotic dose than the oral group (477.3 mg vs 278.6 mg; P < .001), which investigators said may indicate a difference in illness severity between the patient groups.

There was no significant between-group difference in the use of anticholinergic medications to treat extrapyramidal symptoms (22% in the LAI group and 31% in the oral group) despite the LAI group receiving greater doses.

That suggests “that both formulations may be equally as likely to cause these adverse effects,” the researchers noted.

Thirty-day readmission rates are important both medically and financially, investigators noted. In schizophrenia, access to medications and nonadherence are “significant problems.” LAI antipsychotic medications may alleviate some of these burdens but come with a high up-front cost.

“Medication access through pharmaceutical company free trial replacement programs may be an option for facilities with restricted formularies or limited medication funding to decrease 30-day readmissions,” investigators wrote.

“The cost of the injections is far lower than the cost of hospital treatments,” Dr. Greer added in the news release. “And each additional visit to the hospital increases the odds that there will be more visits in the future. Every time someone experiences psychosis, they lose gray matter, and they suffer damage that never heals. That’s why it’s so vital to minimize psychotic episodes.”

Chief limitations of the study included its single-center, retrospective chart review design and small sample size. Also, complete patient medication history was not obtained.

The study had no specific funding. The authors declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Various interventions that improve mood — such as psychological therapy, antidepressants, and exercise — reduce general inflammation and disease-specific biomarkers in people with inflammatory bowel disease (IBD), according to a new study.

“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.

“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”

The study was published online in eBioMedicine.
 

Analyzing Mood Interventions

Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.

Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.

The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.

Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.

Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.

In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.

“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.

Courtesy Dr. Mondelli

Cost Benefit

Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.

Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.

Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.

In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.

“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.

King’s College London

A version of this article appeared on Medscape.com.

Various interventions that improve mood — such as psychological therapy, antidepressants, and exercise — reduce general inflammation and disease-specific biomarkers in people with inflammatory bowel disease (IBD), according to a new study.

“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.

“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”

The study was published online in eBioMedicine.
 

Analyzing Mood Interventions

Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.

Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.

The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.

Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.

Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.

In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.

“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.

Courtesy Dr. Mondelli

Cost Benefit

Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.

Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.

Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.

In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.

“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.

King’s College London

A version of this article appeared on Medscape.com.

Various interventions that improve mood — such as psychological therapy, antidepressants, and exercise — reduce general inflammation and disease-specific biomarkers in people with inflammatory bowel disease (IBD), according to a new study.

“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.

“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”

The study was published online in eBioMedicine.
 

Analyzing Mood Interventions

Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.

Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.

The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.

Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.

Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.

In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.

“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.

Courtesy Dr. Mondelli

Cost Benefit

Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.

Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.

Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.

In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.

“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.

King’s College London

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

More than 1 in 10 individuals between 5 and 24 years of age live with at least one diagnosable mental disorder, suggests a new report that shines a light on the global mental health crisis among young people.

The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.

“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

The study was published online in JAMA Psychiatry.
 

State of Emergency

Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency. 

Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years. 

In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively. 

The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%). 

Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%). 

Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.

Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes. 
 

Youth Mental Health Is Not a Monolith

“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial. 

In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.” 

The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote. 

Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested. 

On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added. 

“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).” 

The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.

A version of this article appeared on Medscape.com.

More than 1 in 10 individuals between 5 and 24 years of age live with at least one diagnosable mental disorder, suggests a new report that shines a light on the global mental health crisis among young people.

The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.

“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

The study was published online in JAMA Psychiatry.
 

State of Emergency

Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency. 

Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years. 

In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively. 

The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%). 

Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%). 

Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.

Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes. 
 

Youth Mental Health Is Not a Monolith

“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial. 

In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.” 

The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote. 

Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested. 

On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added. 

“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).” 

The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.

A version of this article appeared on Medscape.com.

More than 1 in 10 individuals between 5 and 24 years of age live with at least one diagnosable mental disorder, suggests a new report that shines a light on the global mental health crisis among young people.

The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.

“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

The study was published online in JAMA Psychiatry.
 

State of Emergency

Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency. 

Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years. 

In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively. 

The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%). 

Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%). 

Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.

Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes. 
 

Youth Mental Health Is Not a Monolith

“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial. 

In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.” 

The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote. 

Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested. 

On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added. 

“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).” 

The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.

A version of this article appeared on Medscape.com.

TOPLINE:

Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.

METHODOLOGY:

• Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
• At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
• A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
• Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
• The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.

TAKEAWAY:

• At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
• The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
• A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
• Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.

IN PRACTICE:

“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.

SOURCE:

Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.

LIMITATIONS:

The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.

DISCLOSURES:

This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.

A version of this article appeared on Medscape.com.

TOPLINE:

Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.

METHODOLOGY:

• Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
• At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
• A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
• Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
• The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.

TAKEAWAY:

• At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
• The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
• A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
• Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.

IN PRACTICE:

“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.

SOURCE:

Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.

LIMITATIONS:

The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.

DISCLOSURES:

This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.

A version of this article appeared on Medscape.com.

TOPLINE:

Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.

METHODOLOGY:

• Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
• At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
• A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
• Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
• The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.

TAKEAWAY:

• At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
• The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
• A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
• Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.

IN PRACTICE:

“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.

SOURCE:

Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.

LIMITATIONS:

The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.

DISCLOSURES:

This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.