Monday, September 30, 2024

Dementia Diagnosis More Common in Older Adults After Falls Than Other Injuries

A study published today in JAMA Network Open has found that more than 1 in 10 older adults who go to the emergency department (ED) after falling are diagnosed with Alzheimer’s disease and related dementias within a year of their ED visit—a rate higher than observed for other injuries such as a transportation accident.

Alexander J. Ordoobadi, M.D., of Brigham and Women’s Hospital, and colleagues examined Medicaid Fee-for-Service data from 2014 and 2015 for more than 2.4 million patients ages 66 and older who had a traumatic injury that resulted in a visit to an ED. None of the patients had an existing diagnosis of dementia at the time of their hospital visit.

Overall, about half of study patients experienced a fall, while the other half experienced other traumatic events such as cutting/piercing, overexertion, or transportation mishaps. The researchers found that 10.1% of patients with falls were diagnosed with dementia within one year of their fall, compared with 6.1% of patients with other traumatic injuries. After adjusting for variables like patient demographics and medical comorbidities, the researchers calculated that a traumatic fall was associated with a 21% increased risk of a new dementia diagnosis.

Furthermore, falls were associated with a 27% increased risk of a new dementia diagnosis among older adults who lived at home, compared with a 10% increased risk of those who lived in a skilled nursing facility.

The researchers found that 11% of the new dementia diagnoses in the study occurred during the patients’ hospital visit, suggesting that dementia was likely present but undiagnosed at the time of their fall. They noted the possibility that some of the patients who fell also may have had mild cognitive impairment, a precursor to dementia, at the time of their fall.

“The association between falls and incident dementia diagnosis highlights the need for cognitive screening for older adults who experience a fall that results in an ED visit or hospital admission,” Ordoobadi and colleagues wrote. “Implementing cognitive screening after falls will require a multidisciplinary effort involving the breadth of clinicians who care for older adults after a fall, ranging from trauma surgeons to geriatricians and primary care physicians.”

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Short Physical Performance Battery and Mediation of the Effect of Mild Cognitive Impairment on Falls by Community-Dwelling Older Adults.”

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Friday, September 27, 2024

FDA Approves Cobenfy, Antipsychotic With a New Approach to Schizophrenia

The Food and Drug Administration (FDA) yesterday approved Cobenfy (xanomeline and trospium chloride), the first antipsychotic drug approved to treat schizophrenia that does not target dopamine receptors, which has long been the standard of care.

Cobenfy introduces a new approach to treating schizophrenia by selectively targeting muscarinic acetylcholine receptors in the brain; these receptors play a role in cognitive processing.

The FDA’s approval of Cobenfy is supported by data from the EMERGENT clinical program, which includes three placebo-controlled efficacy and safety trials and two open-label trials evaluating the long-term safety and tolerability of Cobenfy for up to one year, according to Bristol Myers Squibb, which manufactures the drug.

In the Phase 3 EMERGENT-2 and EMERGENT-3 trials, Cobenfy met its primary endpoint, demonstrating statistically significant reductions of schizophrenia symptoms compared with placebo, as measured by the Positive and Negative Syndrome Scale total score change from baseline to week five.

According to the FDA, the prescribing information includes warnings that Cobenfy can cause urinary retention, increased heart rate, decreased gastric movement, or swelling of the face and lips. Cobenfy is not recommended for patients with known liver impairment. The most common side effects of Cobenfy are nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, increased heartbeat, dizziness, and gastroesophageal reflux disease.

“This drug takes the first new approach to schizophrenia treatment in decades,” said Tiffany Farchione, M.D., director of the division of psychiatry, office of neuroscience, in the FDA’s Center for Drug Evaluation and Research. “This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.”

Cobenfy is expected to be available by late October, at a cost of about $22,500 per year.

For related information, see the Psychiatric News article “Potential Schizophrenia Medications Point to New Disease Model.”

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Thursday, September 26, 2024

Psychotherapies That Address Suicidality Directly or Indirectly Are Comparably Effective

Psychotherapy can be effective at reducing suicidal ideation and suicide attempts in at-risk individuals—even if the psychotherapy does not directly focus on suicidality, according to a meta-analysis published yesterday in JAMA Psychiatry.

Wouter van Ballegooijen, Ph.D., of Amsterdam University Medical Center, and colleagues combined data from 147 clinical studies (totaling more than 11,000 study participants) comparing psychotherapy (such as cognitive behavioral therapy or family therapy) with control treatments and in which suicidal ideation and/or suicide attempts were reported as outcomes. The studies encompassed both psychotherapies directed at suicidality and those that focused on another psychiatric disorder like depression and indirectly addressed suicidality.

Overall, both direct and indirect psychotherapy were associated with comparable, modest reductions in the severity of suicidal ideation. Direct and indirect psychotherapy were also associated with a 28% and a 32% reduced risk of suicide attempt, respectively.

An analysis of individual therapy types suggested that for direct suicide psychotherapy, cognitive-behavioral therapy was most effective at reducing suicidal ideation while dialectical behavior therapy was best at reducing suicide attempt risk—although van Ballegooijen and colleagues cautioned that the sample sizes for individual treatments were small.

“Suicide prevention strategies could make use of indirect effects. The average proportion of individuals with past-year suicide ideation, plans, or attempts seeking or engaging with mental health services is estimated to be around 30%, and perceived stigma is one of the reasons for this low percentage,” the researchers wrote. “[T]reatments targeting less stigmatizing problems may be a way to provide effective interventions to people who would not likely seek treatment for suicidal ideation or self-harm.

“On the other hand, direct interventions may have additional merit for health care professionals, because they could provide tangible tools and strategies and enhance clinicians’ confidence when dealing with suicidal ideation and attempts,” they added.

For related information, see the Psychiatric News article “Innovative Suicide Prevention Program Using Psychotherapy Shows Early Success.”

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Wednesday, September 25, 2024

National Survey Reveals Clinical, Social Challenges for People With Schizophrenia Spectrum Disorders

People with schizophrenia spectrum disorders (SSD) have high rates of comorbid mental and/or substance use disorders and poor social and economic functioning, yet only a quarter received minimally adequate treatment in the previous year, according to a report in Psychiatric Services.

“These findings further suggest that existing treatment and social welfare approaches are not meeting the needs of many people with schizophrenia spectrum disorders,” wrote Natalie Bareis, L.M.S.W., Ph.D., of the department of psychiatry at Columbia University Irving Medical Center, and colleagues.

The report made use of data from the Mental and Substance Use Disorders Prevalence Study (MDPS), a nationally representative survey funded by the Substance Abuse and Mental Health Services Administration and designed to obtain unbiased and inclusive estimates of the prevalence of mental and substance use disorders among U.S. adults ages 18 to 65 living in households.

The MDPS used trained clinicians to administer the Structured Clinical Interview for DSM-5 to 4,764 individuals. A total of 114 individuals were identified with SSD. Among those, more than half (52%) had a major depressive episode in the previous year, while 35% had one or more comorbid psychiatric disorders. More than one-third had a substance use disorder; the most common were alcohol use (23%) and cannabis use (20%) disorders.

Compared with those without SSD, those with SSD were less likely to have completed college (4% vs. 32%) and less likely to be employed (17% vs. 61%). Those with SSD were also less likely to be married or in a romantic relationship.

Overall, 71% of individuals with lifetime schizophrenia spectrum disorders reported some mental health treatment in the past year—56% had at least one outpatient visit, 9% had an inpatient or residential stay, and 58% were currently taking a psychotropic medication. However, just 26% received minimally adequate treatment—defined as taking one or more antipsychotic medications and having four or more outpatient mental health visits in the past year—despite the fact that most of the individuals had health insurance.

The authors noted that there are several effective, evidenced-based interventions for SSD, including assertive community treatment and coordinated specialty care. “Policies to improve access to and use of existing evidence-based interventions are essential,” they wrote. “Innovative interventions and implementation strategies, along with research to examine their effectiveness, will be critical to improve outcomes for people with schizophrenia spectrum disorders.”

For related information, see the Psychiatric News article “Study Calculates Disability Caused by Schizophrenia.”

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Tuesday, September 24, 2024

Few Jails Offer OUD Medications to Anyone Who Needs Them

Fewer than half of jails in the United States have medications for opioid use disorder (OUD) available within their facilities, according to a National Institute on Drug Abuse (NIDA)–funded study published today in JAMA Network Open. The study also found that only a fraction of jails offered the medications to anyone who had a known diagnosis of an OUD who requested them.

“Offering substance use disorder treatment in justice settings helps to break the debilitating—and often fatal—cycle of addiction and incarceration,” NIDA Director Nora D. Volkow, M.D., said in a press release. “Though someone may be in jail for only a short time, connecting them to addiction treatment while they are there is critical to reduce risk of relapse and overdose, and to help them achieve long-term recovery.”

Elizabeth Flanagan Balawajder, M.P.H., of the University of Chicago, and colleagues analyzed survey responses from 927 jails across the country (prisons were not included). The survey featured 23 multiple-choice questions on jail characteristics and health care offerings.

Overall, 70% of jails surveyed offered some type of substance use disorder support (such as a 12-step program), but only 43.8% offered one or more OUD medications (buprenorphine, naltrexone, or methadone). Further, just 12.8% of jails provided an OUD medication to anyone who requested one; most jails had restrictions, such as requiring that the individual was already taking a medication at the time of booking.

The analysis also showed that smaller jails, jails in areas of greater social vulnerability, and jails that did not have either direct employees or contracted vendors managing health care were less likely to provide OUD medications. The overdose mortality rate of the jail’s county was not associated with the availability of OUD medications, however.

“It is hard to believe but true that in 2024, with all the evidence that [medications for OUD] are associated with reduced death in persons with OUD and the incredibly high level of diagnosed individuals in our jail and community settings, we continue to see a lack of provision of these lifesaving medications to people who need and want them,” Sandra Springer, M.D., of Yale School of Medicine, wrote in an invited commentary. “The medications work, but we as a society need to help remove barriers for people to access these evidenced-based medications wherever they are to end the opioid overdose epidemic now.”

For related information, see the APA blog post “How to Help Those with Opioid Use Disorder in Jails & Prisons.”

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Monday, September 23, 2024

Perceived CTE Linked to Suicidality in Former Football Pros

Former professional football players who believe they have chronic traumatic encephalopathy (CTE) are more than twice as likely to report suicidality, a study in JAMA Neurology has found.

However, there is a catch: chronic traumatic encephalopathy neuropathological changes (CTE-NC) can only be determined at autopsy, so there is no way to tell whether living former football players who perceive themselves as having CTE actually have biological changes indicative of the condition.

“Football players, lay people, clinicians, and popular media outlets often refer to CTE as a singular entity occurring in living and deceased individuals to represent CTE-NC and/or TES [traumatic encephalopathy syndrome – a proposed clinical diagnosis characterized by cognitive impairment and problems controlling behavior] interchangeably,” wrote Rachel Grashow, Ph.D., M.S., of the Harvard T.H. Chan School of Public Health and colleagues. “CTE is often presented as manifesting in living people as cognitive impairment, mood disorders, and suicidality, even though depression and suicidality are not part of the TES core clinical features.”

The researchers examined data from 1,980 participants in the Football Players Health Study, a longitudinal cohort of 4,180 former professional football players launched in 2015. Without providing a definition of CTE, researchers asked the participants in the study sample whether they thought they had the condition. The participants also completed the 9-item Patient Health Questionnaire, which includes a question on recent suicidality.

Overall, 34.4% of the participants in the study sample reported perceived CTE, and of those, 25.4% reported suicidality, compared with 5% of participants without perceived CTE. After adjusting for other predictors of suicidality such as depression, the researchers found that participants with perceived CTE had 2.06 times the odds of reporting suicidality compared with those without perceived CTE.

Participants with perceived CTE were also more likely to have:

  • Higher concussion signs and symptoms
  • Subjective cognitive difficulties
  • Worse symptoms of depression
  • Higher pain intensity
  • Difficulties regulating actions or emotions
  • Low testosterone

The researchers urged caution in interpreting the results because of the way the media and public discourse routinely implicate “CTE” as the underlying cause of suicide and psychiatric problems among former professional football players.

“While the exact effect of this media coverage remains uncertain, it is possible that this has contributed to former [football] players and their physicians concluding that CTE is directly responsible for myriad postcareer health problems,” Grashow and colleagues wrote. “[I]t is critical that the results presented here not contribute to personal, scientific, or societal misattribution of suicidal ideation as a premortem manifestation of CTE-NC.”

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project.”

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Friday, September 20, 2024

Continuation, Maintenance ECT Lower Risk of Readmission After Acute ECT

Patients who receive continuation and/or maintenance electroconvulsive therapy (ECT) treatment after their acute ECT treatment are at lower risk of hospital readmission compared with those who receive acute treatment alone, according to a study in JAMA Psychiatry. The study also found that less than 8% of patients with schizophrenia, schizoaffective disorder, or depression who receive acute ECT receive continuation or maintenance ECT.

Anders Jørgensen, M.D., Ph.D., of Psychiatric Center Copenhagen, and colleagues examined data from 19,994 patients in the Danish Patient Registry who initiated treatment with ECT from 2003 to 2022. They defined ECT treatment as:

  • Acute: Three or more treatments with less than seven days between adjacent treatments
  • Continuation: Three or more treatments with at least seven days and less than 90 days between adjacent treatments after an acute ECT series within a 180-day time frame
  • Maintenance: Ongoing ECT treatments with intervals of at least seven days and less than 90 days between adjacent treatments on day 181 and beyond

Among the 19,994 patients, 7.7% received continuation or maintenance ECT at any time point (5.1% continuation ECT only and 2.6% maintenance ECT). Patients with schizophrenia or schizoaffective disorder were more likely to receive continuation or maintenance ECT than patients with other disorders.

Patients who received continuation or maintenance ECT had a 32% lower risk of hospitalization within six months and a 38% lower risk of hospitalization in the second six months after finishing acute ECT than those who received acute ECT only. Continuation or maintenance ECT did not appear to reduce the risk of suicidal ideation, however.

“The results uniformly point to the clinical advantages of [continuation or maintenance] ECT, as measured by the risk of readmission, and indicate that this treatment option may be underused,” the researchers wrote. “In terms of costs of hospitalization and ECT, [continuation or maintenance] ECT was cost-effective when comparing expenses before vs after the acute ECT series.”

For related information, see the Psychiatric Services article “Barriers to the Implementation of Electroconvulsive Therapy (ECT): Results From a Nationwide Survey of ECT Practitioners.”

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Thursday, September 19, 2024

Professional Monitoring Programs May Help Physicians Return to Safe Practice

Monitoring programs for licensed health care professionals who have engaged in unprofessional sexual behavior can help them successfully return to practice while ensuring patient safety, according to research issued by the Journal of the American Academy of Psychiatry and the Law.

Currently, 47 of 50 states have professional health monitoring programs (PHPs) that provide confidential support services for physicians and sometimes other health care professionals with potentially impairing conditions such as a substance use disorder (SUD) and who may be facing disciplinary action. Potential components of a PHP contract are tailored to individual needs but may include psychiatric and/or SUD treatment, a worksite monitor, chaperone reports, polygraph testing, drug testing, participation in mutual support meetings, and courses on workplace professionalism.

Alexandria G. Polles, M.D., of the Professionals Resource Network, in Fernandina Beach, Florida, and colleagues combed the Florida PHP database between 1982 and 2018, identifying 570 cases in which a physician or other health clinician engaged in unprofessional sexual behavior. Of these, 232 individuals were referred to take part in a PHP, while the rest were deemed ineligible and handled by the licensing board, legal system, or other entities.

Most clinicians referred to the monitoring program for sexual misconduct were married, middle-aged, heterosexual men; 67% were physicians; and consistent with previous studies, the three most common physician specialties involved were adult primary care (23%), psychiatry (11%), and obstetrics-gynecology (4%). Among the monitored group, personality, mood, paraphilias/other sexual, drug use, and alcohol use disorders were most common. The majority of sexual misconduct was directed to current or former patients, and 23% of all incidents involved minors.

Overall, three-quarters of the cases involving monitoring were deemed “very successful” (the individual completed the monitoring contract and there was no further aberrant behavior) or “successful” (completed the monitoring with modification of or extension to the requirements). Only 12% discontinued monitoring against recommendation and relinquished their license, while just 3% were denied licensure or had their license revoked. Compared with health professionals not eligible for a PHP, those with monitoring were less likely to face legal involvement and have their license restricted, relinquished, or revoked.

“Unprofessional sexual behavior by licensed health care professionals is a serious offense that merits full investigation and appropriate consequences. In cases where evaluation results and treatment response suggest that the practitioner would be successful returning to practice without recurrent [unprofessional sexual behavior], referral … may be beneficial,” the researchers wrote. Program “monitoring agreement parameters provide additional safeguards to protect the public from harm while supporting licensed health care practitioners in their return to practice and overall wellbeing.”

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Wednesday, September 18, 2024

Hormone Therapy May Reduce Relapse Risk for Menopausal Age Women With Schizophrenia

Adding menopausal hormone therapy (MHT) to antipsychotic medication can lower the risk of relapse or any psychiatric hospitalization in women between 40 and 62 years of age who have schizophrenia, according to a report in AJP in Advance.

“At menopausal age, antipsychotic effectiveness decreases and relapse risk increases,” wrote Bodyl A. Brand, M.Sc., of the University Medical Center Groningen, the Netherlands, and colleagues. “Higher dosages do not effectively prevent relapse, while they do increase the risk for side effects…. The current study provides evidence that, while accounting for antipsychotic use, augmentation with MHT may provide a better strategy for relapse prevention.”

The researchers analyzed data from 3,488 women in Finland diagnosed with schizophrenia or schizoaffective disorder (SSD) and hospitalized for psychosis who initiated systemic MHT between 1995 and 2017.

The researchers used a within-person study design that compared the rates of health outcomes during periods when the women were taking MHT and periods when they were not. The primary outcome was relapse, defined as hospitalization due to psychosis; the secondary outcome was hospitalization due to any psychiatric reason.

A total of 1,849 women (52.7%) had at least one hospitalization for psychosis during follow-up. Overall, women using MHT were 16% less likely to relapse than those not using MHT. Hospitalization for any psychiatric reason was also lower when MHT was used.

The reduced risk of relapse was greatest for women who started MHT between ages 50 and 55, followed by women who began between ages 40 and 49; there was no reduced risk for women who started between ages 56 and 62.

There were some slight differences in effectiveness among various hormonal formulations. Estradiol alone as well as estrogen plus levonorgestrel, medroxyprogesterone acetate, or norethisterone were associated with between 15% and 25% reduced relapse risk, while estriol, tibolone, and estrogen plus dydrogesterone were not associated with decreased relapse risk. Oral and transdermal formulations appeared to be similarly effective.

“To maximize benefits and minimize risks of MHT, treatment should be individualized using the best available evidence, with periodic reevaluation of continuation,” the authors concluded. “Women with SSD of menopausal age form an exceptional group which is susceptible to psychosis relapse, but also to side effects of antipsychotic medication…. Considering its potential and safety, continued efforts are needed to make MHT more accessible and acceptable in this vulnerable group of women.”

For related information, see the Psychiatric News article “Can Hormonal Treatments Help Your Patients?”

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Tuesday, September 17, 2024

Most Adults in a Religious Community Would Seek Mental Health Care if Faith Leader Advised It

Nearly seven in 10 adults who belong to a religious community would likely seek mental health care if a leader in their religious community recommended it, according to APA’s latest Healthy Minds poll.

The online poll, conducted on behalf of APA by Morning Consult on August 16 and 17, asked 2,201 adults for their thoughts on faith and mental health and found:

  • 72% of Black adults, 70% of White adults, and 63% of Hispanic adults who belonged to a religious community would seek mental health care if a religious leader recommended it.
  • 57% of adults who belonged to a religious community said they would likely reach out to a faith leader if they were struggling with their mental health.
  • 52% of adults who belonged to a religious community said their religious community discusses mental health openly and without stigma.

“Many of us rely on our faith communities for support in times of mental and emotional difficulty, whether we are struggling ourselves or we are supporting a loved one with a mental health condition,” said Marketa M. Wills, M.D., M.B.A., CEO and Medical Director of APA. “When a faith leader supports and encourages conversations around mental health, it makes a difference to that community, and as psychiatrists we welcome that approach.”

In conjunction with the poll, the APA Foundation is releasing the second edition of its resource guide “Mental Health: A Guide for Faith Leaders.” The resource guide provides faith leaders with insights and tools to understand mental health concerns and support congregants with mental health challenges, adapting the APA Foundation’s existing Notice. Talk. Act.® framework for a faith community setting and offering advice to faith leaders on caring for themselves to avoid compassion fatigue. The updated guide also provides some noteworthy post-pandemic tools and resources.

For related information, see the Psychiatric News article “Partnership Between Psychiatrists, Faith Leaders Untapped Key to Expanding Reach of MH Care.”

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Monday, September 16, 2024

Emotional Tone of Written Statements Can Predict Worsening Depressive Symptoms

The emotional tone, or sentiment, conveyed in writing can be predictive not only of an individual’s current mood but also future changes in mood, according to a report published today in PNAS. Further, both human reviewers and AI tools were able to predict future depressive symptoms based on a sentiment analysis of written statements.

Jihyun K. Hur, M.A., of Yale University, and colleagues developed nine open-ended questions based on the nine-item Patient Health Questionnaire (PHQ-9), which screens for depressive symptoms. The questions were phrased to remove any negative framing. For example, the question related to fatigue was: “Sometimes we feel tired and exhausted, and sometimes we feel full of energy. How would you describe your energy level in the past 2 weeks?”

Hur and colleagues then invited 467 participants to answer the open-ended mood questions; the participants also completed the standard PHQ-9 a day before and three weeks after they offered their written narratives. The researchers also enrolled 470 additional participants to act as sentiment raters; each rater was given a random subset of responses and asked to rate the positivity and negativity of each statement from zero to 10 using predefined criteria. The sentiment of written responses was also assessed by Linguistic Inquiry and Word Count (a text assessment tool) and ChatGPT (a large language learning model) using the same criteria.

Not surprisingly, individuals with higher baseline PHQ-9 scores were more likely to write narratives with high negative sentiment across all three rating methods. However, even after factoring in individuals’ baseline mood symptoms, high negativity ratings as calculated by human raters or ChatGPT were reliably associated with worsening depressive symptoms at the three-week follow-up.

“These findings underscore the potential of using automated text analysis tools to improve psychological assessments at minimal cost. Our analysis expenses were almost free, less than 0.1 cents per individual based on current GPT-3.5 prices,” Hur and colleagues wrote. “Future research is needed to examine whether our approach can be used to monitor and predict symptoms in clinical populations diagnosed with depressive disorders including those with severe symptoms.”

For related information, see the Psychiatric Services article “Machine Learning–Based Evaluation of Suicide Risk Assessment in Crisis Counseling Calls.”

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Friday, September 13, 2024

Brief Inpatient CBT Significantly Lowers Future Suicide Attempt Risk, Study Finds.

Adding four sessions of cognitive-behavioral therapy (CBT) to standard suicide prevention treatment at an inpatient hospital can significantly reduce the risk of future suicide attempts, reports a study in JAMA Psychiatry. Among psychiatric inpatients without a substance use disorder (SUD), brief CBT was also found to significantly reduce the risk of hospital readmission.

Gretchen J. Diefenbach, Ph.D., of Yale University School of Medicine, and colleagues randomized 200 adults admitted to a private psychiatric hospital in Connecticut to receive either treatment as usual (n = 106) or usual treatment plus brief CBT (n = 94) during their stay. Study participants—recruited between January 2020 and February 2023—all had a suicide attempt within one week of admission or current suicidal ideation along with a suicide attempt in the past two years. Although adults with current mania or a history of schizophrenia were excluded from participation, individuals with an existing SUD were included, comprising 60% of participants.

Usual treatment entailed 24-hour multidisciplinary care that included safety planning, psychosocial services, and medications as needed. The CBT group also received up to four individual CBT sessions (depending on length of stay) that included components such as developing a crisis response plan, inventorying reasons for living, creating a hope kit, and reducing access to lethal means.

The researchers conducted monthly follow-up assessments with participants upon discharge for six months; overall, 114 participants completed the full six months of assessments.

At six months, participants who had received brief CBT had 60% lower odds of a suicide attempt compared with those only receiving usual treatment. Participants in the CBT group also reported lower levels of suicidal ideation, although only at one and two months post-discharge.

Brief CBT was also associated with 71% decreased odds of psychiatric readmission at six months among participants who did not have an SUD at admission. “These findings are consistent with previous research identifying SUD as a suicide risk factor and poor prognostic indicator,” Diefenbach and colleagues wrote. “Research is needed to disentangle the complex and bidirectional interplay between substance use and its medical, social, and psychiatric correlates to inform the development of SUD-specific treatment enhancements in the future.”

The researchers acknowledged that broad uptake of inpatient CBT is a challenge. “In addition to short lengths of stay, workflows can be chaotic, with frequent, often abrupt changes in schedules and discharge plans,” they wrote. “Dissemination of this treatment protocol may not be possible without substantial hospital investment, for example, by creating new positions for specialist suicide prevention staff, who have been trained to administer the [brief] CBT-inpatient protocol with high fidelity.

“Alternatively, adaptations … such as administration by nonexpert clinicians, utilizing a group format, or integrating the use of technology such as mobile applications, may be needed before widespread uptake can occur.”

For related information, see the Psychiatric News article “Peer Specialists Can Aid in Suicide Prevention.”

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Thursday, September 12, 2024

Prescription Amphetamines Pose Dose-Dependent Risk for First-Time Psychosis or Mania

Young people taking prescription amphetamines were nearly three times more likely to develop first-episode psychosis or incident mania than those taking methylphenidate, according to a study issued today by AJP in Advance.

The Food and Drug Administration added warnings to prescription stimulant labels in 2007 after studies showed they increased risk of psychotic or manic symptoms, even among patients with no history of these symptoms. Despite a more than five-fold increase in prescribing rates in the past two decades, “there are currently no published studies to guide prescribers on dose levels and other factors that impact the rare but serious risk,” wrote Lauren V. Moran, M.D., M.P.H., of McLean Hospital in Belmont, Massachusetts, and colleagues.

Moran and colleagues analyzed health records for first-time inpatients aged 16 to 35 years at McLean Hospital between 2005 and 2019. They matched 1,374 individuals who were experiencing initial psychosis or new onset mania with 2,748 admitted with other diagnoses.

After factoring in other substance use, patient psychiatric history, and other variables, the researchers found that patients with any past-month prescription amphetamine use were 2.7 times more likely to develop psychosis or mania than those with no use. Patients taking high doses of amphetamines—defined as >30 mg dextroamphetamine or equivalent (40 mg of mixed amphetamine salts or 100 mg of lisdexamfetamine)—were 5.3 times more likely to have psychosis or mania. Patients aged 23 years or older had higher odds of psychosis or mania than younger patients, possibly due to the higher average amphetamine dose researchers observed in the older group.

Moreover, patients taking prescription amphetamines were 2.85 times more likely to experience incident psychosis or mania than those taking methylphenidate. Those taking methylphenidate did not have increased odds of psychosis or mania than those not taking these medications, researchers noted.

“Our results suggest that prescription amphetamine dose is the most important modifiable factor associated with stimulant-related psychosis or mania…. Our findings suggest that clinicians can mitigate the risk of psychosis or mania by avoiding doses above 30 mg dextroamphetamine equivalents,” Moran and colleagues wrote. “In patients who experience impairment from ADHD symptoms who may benefit from doses above 30 mg dextroamphetamine equivalents, careful monitoring with screening for symptoms of psychosis or mania is critically warranted.

“This is of particular importance given that psychosis and mania are often associated with lack of insight,” the researchers continued. “Symptoms that develop in the context of prescription amphetamine use could emerge without the patient’s awareness, leading to a delay in detection.”

For related information, see the Psychiatric News article “Study Finds Higher Risk of Psychosis With Amphetamines for ADHD.”

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Wednesday, September 11, 2024

COVID Lockdowns May Have Accelerated Brain Aging in Adolescents, Especially Females

Young females may have experienced significant brain changes as a result of disruptions of social life caused by the COVID-19 pandemic, according to a report in PNAS.

An analysis of MRI images taken before and after the pandemic revealed accelerated thinning in regions of the frontal cortex among a sample of children and adolescents. This thinning was observed in both sexes but was more widespread and of greater magnitude in females.

“As accelerated cortical thinning during brain development is associated with increased risk in the development of neuropsychiatric and behavioral disorders, the findings from this study highlight the importance of providing ongoing monitoring and support to adolescents who experienced the pandemic lockdowns,” wrote Patricia Kuhl, Ph.D., and colleagues at the University of Washington.

The researchers collected MRI data in 2018 from 160 Seattle-area adolescents aged 9, 11, 13, 15, and 17; none of the adolescents had a diagnosis of a developmental or psychiatric disorder or were taking psychotropic medication. The authors collected MRI data again in 2021 and early 2022 from 130 of these youths, now aged 12, 14, 16, 18, and 20.

Kuhl and colleagues used a subset of the pre-COVID-19 MRI data to model the expected change in cortical thickness between the ages of 9 and 17. They then compared this model of normal change over time to the observed cortical thinning of 54 participants who were 12, 14, or 16 during the second MRI scan and whose baseline scans were not used to generate the model.

The comparison revealed widespread cortical thinning throughout the female brain in post-COVID-19 scans, occurring in 30 brain regions associated with social cognition; in males, thinning was limited to two brain regions associated with visual processing of faces. Among females, the magnitude of accelerated thinning was equal to 4.2 years of aging, compared with 1.4 years in males.

The authors noted that accelerated brain development has long been associated with social stress such as deprivation and neglect; they suggested that, for females, peer relationships are vital for the development of self-identity because they rely on these relationships for emotional support more than males. “The effect of the resulting isolation on the needs of male and female adolescents may have been very different, with females perhaps experiencing more stress than males associated with this prolonged isolation,” they wrote.

Kuhl and colleagues concluded: “…[T]hese findings add evidence for the necessity of new public health campaigns to provide support for adolescents and young adults struggling with mental health challenges, as the pandemic lockdowns dramatically increased the incidence of these types of disorders.”

For related information, see the Psychiatric News article “After the Pandemic, What Will the ‘New Normal’ Be in Psychiatry?”

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Tuesday, September 10, 2024

Cerebrospinal Fluid May Not Be Contained to Cerebrospinal Region

A study published in Science Advances provides evidence that cerebrospinal fluid (CSF) is not contained to the brain and spinal cord—it can potentially travel throughout the nervous system.

“Our results support a contiguous and continuous CSF flow system from the CNS [central nervous system] to the distal ends of peripheral nerves, a function likely integral in sustaining peripheral nerves through delivery of nutrients and removal of waste,” wrote Alexander P. Ligocki, Ph.D., of the University of Florida, and colleagues.

Ligocki and colleagues injected tiny gold particles (about 2 nanometers in size) containing a tracer dye into the lateral ventricles—CSF-filled chambers within the brain—of laboratory mice. While the particles initially dispersed across the brain and spinal cord, within four to six hours they had spread into peripheral nerves such as the trigeminal nerve that controls facial sensations and the sciatic nerve that runs down the back of each leg. The particles were contained in the endoneurium—a fluid-filled sheath of connective tissue that surrounds nerve bundles.

Larger, 15-nanometer gold particles did not escape the central nervous system but collected in the brainstem and spinal cord near the origins of peripheral nerves. The researchers also injected the tiny gold particles into the veins of the mice and did not observe any tracer dye in peripheral nerves, indicating the particles were not passing through the blood-brain barrier and traveling through the blood stream.

“The presence of a contiguous CSF flow route from the CNS along peripheral nerves has far-reaching implications for peripheral nerve health and neuropathologies,” Ligocki and colleagues wrote. They noted, for example, that a continuous flow system may explain why diseases like Alzheimer’s or Parkinson’s can be associated with loss of feeling in the hands or feet—because disturbances in CSF pressure in the brain will spread throughout the body.

“Furthermore, our results suggest that infusion into the CSF compartment may be an efficacious method for direct delivery of drugs and therapeutic agents to peripheral nerves,” the researchers added.

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Monday, September 9, 2024

APA Applauds New Final Rules Strengthening Mental Health Parity

Today, the Biden-Harris administration issued final rules that strengthen the 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) with the goal of improving people’s access to quality mental health and substance use disorder care. Issued by the U.S. Departments of Labor, Treasury, and Health and Human Services, the rules reinforce that insurance plans must ensure that mental health care benefits are no more restrictive than those medical and/or surgical benefits.

“APA has always been a strong advocate for mental health parity, and since its enactment, APA has worked tirelessly to advocate for compliance with and enforcement of the federal parity law,” APA CEO and Medical Director Marketa M. Wills, M.D., M.B.A., said in a statement applauding the rules. "This is a big step forward to hold insurance plans accountable by ensuring the law’s intent is fulfilled and that more individuals will be able to access the mental health and substance use treatment they need.”

Specific provisions in the final rules—which represent the first significant update to the MHPAEA in nearly a decade—include:

Health plans must evaluate their provider networks, out-of-network payment rules, and prior authorization policies, and make changes to reach compliance with the MHPAEA where needed—such as adding more mental health care providers or increasing reimbursement rates.

Health plans cannot use more restrictive prior authorization or other medical management techniques, nor make use of any discriminatory information, to reduce access to mental health and substance use disorder benefits relative to other medical benefits.

Non-federal government health plans (e.g., plans offered to state and local government employees) are no longer exempt from MHPAEA compliance. This change will improve parity for around 120,000 individuals across 200 health plans.

Most of these provisions will take effect on January 1, 2025.

For related information, see the Psychiatric News article “Government Proposes New Rules to Strengthen Parity Law.”

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Friday, September 6, 2024

Researchers Propose Olanzapine and Perphenazine as First-Line Schizophrenia Treatments

Along with aripiprazole and risperidone, olanzapine and perphenazine should be considered first-line antipsychotics for patients with schizophrenia, according to a clinical perspective published in Schizophrenia.

“Clinicians face challenges in balancing efficacy and side effects when prescribing antipsychotics to treatment-naive patients,” wrote Matej Markota, M.D., and colleagues at Mayo Clinic in Rochester, Minnesota. “Existing algorithms approach this issue by assigning high significance to a few side effects, such as weight gain and/or tardive dyskinesia, commonly leading to exclusion of agents such as olanzapine and first-generation antipsychotics (FGAs), respectively, as first-line treatments.”

In the article, Markota and colleagues suggested physicians should focus instead on three overlapping factors:

  • Overall efficacy, particularly long-term efficacy since schizophrenia is a disorder requiring long-duration treatment.
  • All-cause discontinuation as a surrogate for side-effect burden rather than weighing one or two side effects.
  • Mortality risk, which factors in medication effectiveness, discontinuation rate, and long-term burden of reported side effects, such as the cardiovascular implications of excess weight gain.

When considering those factors, the researchers noted that clinical trials have shown olanzapine demonstrates superior efficacy as well as low discontinuation rates compared with risperidone or aripiprazole. Olanzapine does have a high risk of weight gain, but available data does not suggest it increases mortality relative to other medications. Given its demonstrated effects on hostility, the researchers believe olanzapine is a preferred first-line choice for patients for whom aggression may be a concern, with clozapine as a second-line medication.

Meanwhile, perphenazine has typically been overlooked due to the risks of extrapyramidal symptoms like tardive dyskinesia (TD) among first-generation antipsychotics. “However, there is considerable variability in TD risk within FGA and second-generation antipsychotic classes, a nuance frequently ignored by other algorithms,” Markota and colleagues wrote. “Perphenazine has one of the lowest known risks of TD among FGAs.” This medication also has a favorable metabolic and weight gain profile, they noted.

Markota and colleagues stressed that their medication rationale was for a “general” patient: “[W]hen idiographic factors of individuals dictate a different approach, the considerations discussed here should defer to individualized plans, and patients and practitioners should engage in shared decision-making at every step.”

For related information, see the Psychiatric News article “Clozapine Found Most Effective in Patients With Schizophrenia and Conduct Disorder.”

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Thursday, September 5, 2024

Researchers Find Lack of Systemic Adverse Event Reporting in Psychedelics Research

About 4% of individuals with a neuropsychiatric disorder had a serious adverse event—including worsening depression, suicidal behavior, psychosis, or convulsions—after being given a “classic” psychedelic as part of a research study, according to a meta-analysis that spanned some 75 years issued by JAMA Psychiatry. The meta-analysis identified no such adverse events among healthy participants; at the same time, tracking of such events should be improved, the study researchers wrote.

“Recording aversive experiences as adverse events is pragmatic and necessary. In particular, the presence and absence of any [adverse events] … such as precipitation of an affective or psychotic illness, persisting perceptual disturbances, and cardiac toxicity, should be clearly reported,” wrote Jared T. Hinkle, M.D., Ph.D., of Johns Hopkins University School of Medicine, and colleagues. “…Our results broadly indicate that while medically or psychiatrically significant adverse events, for example, psychosis [or] suicidality, are relatively rare, these events are often serious when they occur."

Hinkle and colleagues examined 214 clinical or research studies going back to 1951, for which 53% (114 studies) reported analyzable adverse event data. These studies included 1,726 healthy participants, 934 participants receiving outpatient psychiatric care, and 844 participants receiving inpatient psychiatric care; all participants received high doses of one of the four most actively studied psychedelics: LSD (lysergic acid diethylamide), psilocybin, DMT (dimethyltryptamine), or 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine). All studies involving inpatients were done prior to 1970, researchers noted.

Results were as follows:

  • In contemporary research studies (since 2005), there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders.
  • Of 584 outpatient participants administered high-dose psilocybin, three exhibited delayed suicidal behaviors; all three individuals had treatment-resistant depression.
  • Reports of other adverse events requiring medical intervention, such as paranoia or headache, were rare.
  • Just two serious acute events (within 48 hours of psychedelic effect) were identified in outpatient participants: One person given LSD in a study of anxiety experienced “acute transient anxiety and delusions” refractory to lorazepam, which required olanzapine and overnight observation, and one participant with depression and a history suggestive of orthostasis given DMT experienced a substantial blood pressure drop.

The researchers cautioned that only 29% of contemporary studies with adverse event data reported all adverse events, as opposed to only listing adverse drug reactions. This could explain the lower-than-expected reported rate of certain adverse events—for example, visual hallucinations—among participants. The researchers also noted that individuals with psychotic or manic disorders are typically excluded from contemporary research studies.

“Although psychedelic treatments were initially very well tolerated in participants with psychiatric conditions, the rate of potentially life-threatening delayed adverse events was higher in participants with psychiatric conditions than those without. The reasons for this remain undetermined,” Hinkle, a PGY-2 psychiatry resident at Johns Hopkins Hospital, told Psychiatric News Alert via e-mail. “Also, these data do not generalize to psychedelic use outside of a clinical or research context, so psychiatrists should advise their patients accordingly.”

For more information, see the Psychiatric News article “Psychedelic Use in Psychiatry Demands New Informed Consent Process, Bioethicists Say.”

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Wednesday, September 4, 2024

Patients Without Psychiatric Illness Likely Not at Risk for Depression, Suicidal Behavior With Semaglutide

People without known major psychiatric illness who are treated with semaglutide for obesity do not appear to be at increased risk for depression or suicidal thinking or behavior compared to patients receiving a placebo, according to a report yesterday in JAMA Internal Medicine.

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that has been shown to produce clinically significant weight loss in patients with obesity or Type 2 diabetes. However, both the Food and Drug Administration and the European Medicines Agency have been monitoring the safety of GLP-1 receptor agonists following postmarketing surveillance reports of depression and suicidal ideation in people prescribed these medications, noted Thomas Wadden, Ph.D., of the University of Pennsylvania Perelman School of Medicine, and colleagues.

Wadden and colleagues analyzed pooled data from four phases of the Semaglutide Treatment Effect in People with Obesity (STEP) trial that tested 2.4 mg of semaglutide in patients with obesity. (One phase of the trial also included patients with Type 2 diabetes.). The STEP trial excluded participants who had a history of severe psychiatric illness—such as major depression or schizophrenia—or suicide attempt, as well as individuals who screened for elevated depressive symptoms or suicidal ideation within the past 30 days. The original STEP trial and this secondary analysis were funded by Novo Nordisk A/S, and researchers from the company were involved in this analysis.

The analysis included 3,681 patients (73% female). Across the four trials, only 2.8% of patients treated with semaglutide had a postbaseline Patient Health Questionnaire score of 15 or greater—suggestive of moderately severe or greater symptoms of depression requiring evaluation by a mental health professional—compared with 4.1% of those receiving placebo. Suicidal ideation as assessed by the Columbia–Suicide Severity Rating Scale was less than 1% in all trials, with no differences between treatment groups.

Wadden and colleagues noted that a small number of patients taking semaglutide may experience depression or suicidal thoughts “which may be related to psychosocial complications of obesity or other factors, including life stressors.”

They concluded: “We encourage clinicians to monitor mental health in people with overweight or obesity, including those prescribed semaglutide, 2.4mg, or similar medications. This is essential for ensuring that these individuals obtain the psychiatric care they require to manage anxiety, depression, and related psychiatric complications, which may occur in the presence or absence of weight management interventions.”

In another study published in JAMA Internal Medicine yesterday, Peter Ueda, M.D., Ph.D. at Sweden’s Karolinska Institutet and colleagues analyzed nearly a decade of patient data from Swedish and Danish health registries and found no evidence that GLP-1 RAs increased the risk of suicide death in adults relative to those who took another class of diabetes medications (sodium-glucose cotransporter-2 inhibitors).

For more information, see the Psychiatric News article “Blockbuster Weight Loss Drugs Not Tied to Suicidality, Studies Show.”

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Tuesday, September 3, 2024

Cannabis Use Linked to Absenteeism at Work

Cannabis use disorder (CUD) and frequent cannabis use are linked to greater absenteeism at work, a study in the American Journal of Preventive Medicine has found.

Kevin H. Yang, M.D., of the University of California, San Diego, and colleagues analyzed data from 46,499 adults who were employed full-time and participated in the National Survey on Drug Use and Health from 2021 to 2022. Participants were asked if they had ever used cannabis and, if yes, how recently. Those who used cannabis in the past month were asked how often. Proxy diagnosis of CUD and CUD severity were determined using standardized items corresponding to DSM-5 criteria. Participants were then asked how many days of work they had missed in the past month because they were sick or injured and how many days of work they had missed because they “just didn’t want to be there.”

Overall, an estimated 15.9% of participants used cannabis in the past month. In addition, 4.0%, 1.6%, and 0.9% met criteria for mild, moderate, and severe CUD, respectively. Participants who used cannabis in the past month had a mean 1.47 days of missed work because of illness or injury, compared with 0.95 days for those who never used cannabis. Participants who used cannabis in the past month had a mean 0.63 days of skipping work compared with 0.28 days for those who had never used cannabis. Individuals who met the criteria for any CUD were more likely than those without CUD to miss or skip work, with the latter showing a stepwise increase as CUD severity increased.

Yang and colleagues wrote that cannabis use has been linked to anxiety, panic attacks, depression, sleep disturbances, respiratory issues, and vehicle accidents, all of which could contribute to increased absenteeism due to illness or injury. They added that individuals who are injured or ill may turn to cannabis for self-medication, potentially exacerbating the cycle of absenteeism.

The researchers noted that cannabis consumption may lead to reduced motivation and cognitive changes, which may partially explain why individuals who use cannabis are more likely to skip work. They added that such associations may be bidirectional, where individuals wanting to skip work may be more inclined to use cannabis because of factors such as boredom.

“These findings underscore the need for targeted interventions, workplace prevention policies, and further research to mitigate the negative consequences of cannabis use on work productivity and overall public health,” Yang and colleagues concluded.

For related information, see the Psychiatric News article “SUDs Cost Employer Health Insurance $35 Billion Per Year.”

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