Subtle Cognitive Deficits May Precede Amyloid Accumulation in Alzheimer’s, Study Suggests

In the progression of Alzheimer’s disease (AD), subtle cognitive difficulties may develop prior to or alongside the early phases of amyloid accumulation, according to a study published Monday in Neurology. The findings challenge the hypothesis that amyloidosis (the buildup of amyloid proteins) comes first in the Alzheimer’s disease process.

Kelsey R. Thomas, Ph.D., of the VA San Diego Healthcare System and colleagues analyzed data from 747 people aged 55 to 90 without dementia who participated in the Alzheimer’s Disease Neuroimaging Initiative. The participants received PET imaging to determine amyloid levels at baseline, then each year over four years.

The researchers evaluated the cognitive abilities of the participants using memory, language, and attention tests at the beginning of the trial. In addition to examining the total score the participants earned on the cognitive tests, the researchers also gauged if the participants appeared to demonstrate errors in the processes used to complete the tasks. Based on these tests, the researchers divided the participants into three groups: those who were cognitively normal, those with mild cognitive impairment (MCI), and those with subtle cognitive difficulties.

Baseline amyloid levels did not statistically differ between the participants who were cognitively normal or had subtle cognitive difficulties, but those with subtle cognitive difficulties showed faster rates of amyloid accumulation over the four-year study. Additional analysis revealed that participants in the MCI and subtle cognitive difficulties groups had faster thinning of the entorhinal cortex (a brain region known to be impacted early in the progression of Alzheimer’s disease) relative to the cognitively normal group.

“[O]ur study demonstrated a method to successfully detect subtle differences in thinking and memory either before or during the phase when amyloid is accumulating at a faster rate,” Thomas said in a press statement. “This could lead to noninvasive screenings that may be able to detect very early who is at risk of developing Alzheimer's disease.”

In an editorial accompanying the study, Beth E. Snitz, Ph.D., and Adam M. Brickman, Ph.D., of the University of Pittsburgh wrote of the importance of cognitive tests in Alzheimer’s research: “Despite the recent emphasis on characterizing [Alzheimer’s disease] based on biomarker profiles alone, it is critical to emphasize that it is the cognitive deficits and associated functional impairment that are most problematic for patients and their families, and, as illustrated in the Thomas et al. study, highly predictive of the course of the disease. There is thus a great need to continue to focus on cognition, including the implementation and development of methods that push the boundaries of early detection.”

For related information, see the Psychiatric News article “Are Amyloid and Tau Good Biomarkers For Alzheimer’s Disease?”

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FDA Program for Reducing Unsafe Opioid Prescribing and Adverse Events Fails to Produce Clear Results

It is unclear whether the government’s strategy for reducing unsafe opioid prescribing and adverse events associated with opioids is working, according to a report published today in JAMA Internal Medicine. The findings were based on an analysis of documents obtained from the Food and Drug Administration (FDA).

To reduce risks associated with extended-release/long-acting (ER/LA) opioids, the FDA in 2012 mandated a Risk Evaluation and Mitigation Strategy (REMS) for ER/LA products. The REMS required ER/LA manufacturers to offer continuing education to health care providers on safe prescribing of ER/LA opioids, develop medication guides to inform patients about risks of the medications, and monitor and annually report on prescribing behavior and adverse events, according to the report.

“[T]he ER/LA REMS was intended to be the FDA’s primary tool ‘to reduce serious adverse outcomes resulting from inappropriate prescribing, misuse, and abuse,’” wrote James Heyward, M.P.H., of Johns Hopkins Bloomberg School of Public Health and colleagues. The researchers analyzed assessments conducted by drug companies participating in the ER/LA REMS program and other relevant documents, obtained from the FDA through a Freedom of Information Act request.

Findings from the analysis include the following:

• The REMS goal was for 60% of ER/LA opioid prescribers to take a REMS-adherent continuing education course between 2012 and 2016. The data revealed 27.6% of prescribers had done so by 2016.
• A review conducted by the FDA following 36 months of the REMS program concluded that data on prescribing behavior—which were derived from national prescription claims databases and prescriber and patient surveys—were inadequate to assess whether the REMS was meeting its goals in reducing inappropriate prescribing. (The FDA discontinued the analysis after 36 months.)
• In reports following 36, 48, and 60 months of the REMS program, the FDA noted it was unable to assess if the REMS program was reducing ER/LA-related adverse events based on the data submitted by the companies because of a lack of studies directly examining the association between participation in REMS training and changes in clinical practice.

“Instead of bold, effective action, the FDA has implemented the Risk Evaluation and Mitigation Strategy programs that, as shown in the article by Heyward and colleagues … do not even meet the limited criteria set out by the FDA,” William K. Hubbard, M.A., a former FDA official, wrote in an editorial. Hubbard described actions the FDA could take to control opioid prescribing, manufacturing, and distribution.

“One intervention that has shown promise in reducing opioid abuse is restriction on prescribing,” he wrote. “Florida, once known for pill mills, has banned pain management clinics from dispensing drugs and established requirements for medical examinations and follow-ups before and after prescribing opioids for chronic pain, resulting in a two-thirds reduction in pain clinics. … As Florida did, the FDA could restrict distribution of prescription opioids.”

For related information, see the Psychiatric News article “Study Finds REMS Program for Fentanyl Formulation Inadequate.”

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Get Ready for APA’s 2020 Election; Voting Begins January 2!

Voting members of APA will receive their ballots soon for APA’s 2020 election. Information about the candidates can be found on APA’s election website – members may also log in here and vote during the January 2-31 election period. Videos of the candidates for president-elect, treasurer, and trustee-at-large responding to questions posed by APA’s Election Committee will be posted on the APA election website by January 2, the day voting begins. Don’t let this opportunity to influence APA’s future pass you by—be sure to vote.

Many U.S. Counties Have No Child Psychiatrists, Study Finds

Though the total number of child psychiatrists in the United States increased between 2007 and 2016, a shortage remains in large swaths of the country, particularly in lower-income areas, according to a study published in Pediatrics.

“More than half of the children in the United States with a treatable mental health disorder do not receive treatment from a mental health professional,” wrote Ryan K. McBain, Ph.D., M.P.H., of the RAND Corporation and colleagues. “One of the driving factors contributing to this unmet need is a shortage in child psychiatrists.”

McBain and colleagues examined data from the Area Health Resource Files of the Department of Health and Human Services to compare the numbers of child psychiatrists by county between 2007 and 2016. The researchers relied on data from U.S. Census Bureau to calculate the ratios of child psychiatrists per 100,000 children (youth aged 0 to 19) for the 10-year period. Additionally, they compiled county-level data on sociodemographic characteristics of the population, including income, education, and employment.

“Between 2007 and 2016, the number of practicing child psychiatrists in the United States increased from 6,590 to 7,991: a 21.3% gain,” the authors wrote. Additional findings included the following:

• The ratio of child psychiatrists grew from 8.01 per 100,000 children in 2007 to 9.75 per 100,000 children in 2016.
• State-level growth in the number of child psychiatrists varied, with the number of child psychiatrists per 100,000 children increasing by more than 50% in six states (Alaska, Arkansas, Nevada, New Hampshire, Oklahoma, and Rhode Island) and declining in six other states (Idaho, Indiana, Kansas, North Dakota, South Dakota, and South Carolina).
• Child psychiatrists were significantly more likely to practice in counties with higher levels of income and college graduates.

“Although the density of child psychiatrists has increased from 2007 to 2016, there remain ∼70% of counties in the United States with no child psychiatrists,” McBain and colleagues wrote. “The distribution of child psychiatrists also remains inequitable, with a state like Massachusetts having as many child psychiatrists as Oklahoma, Indiana, Georgia, Mississippi, and Tennessee combined, despite these latter states having 5 times as many children ages 0 to 19.”

They concluded, “[C]ounties with few or no child psychiatrists may need to look to alternative or complementary frameworks to address child mental health needs, including integration of behavioral health in pediatric primary care settings, school-based mental health services, child psychiatry telephone consultation access programs, and new models of telepsychiatry.”

For related information, see the American Journal of Psychiatry Resident’s Journal article “The Winding Road to Training in Child Psychiatry: Considering a New Path” and the Psychiatric Services article “Impact of Child Psychiatry Access Programs on Mental Health Care in Pediatric Primary Care: Measuring the Parent Experience.”

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FDA Approves Caplyta to Treat Schizophrenia in Adults

The Food and Drug Administration (FDA) this week approved Caplyta (lumateperone), an oral atypical antipsychotic medication to treat schizophrenia in adults.

“Schizophrenia is a complex disease that severely impacts patients and their families,” Jeffrey A. Lieberman, M.D., the Lawrence C. Kolb Professor and Chairman of Psychiatry at Columbia University, said in a statement. “Effective treatment provided in a timely fashion can be game-changing for people living with schizophrenia. The efficacy and safety profile of Caplyta … offers health care providers an important new option for treating people living with schizophrenia.”

The approval of Caplyta was supported by two four-week, placebo-controlled trials involving a total of 785 adults with schizophrenia. In both trials, patients receiving 42 mg lumateperone achieved a statistically significant reduction in the Positive and Negative Syndrome Scale (PANSS) score at the end of 28 days compared with placebo. In the first trial, the PANSS score decreased 13.2 points in the treatment group compared with 7.4 points in the placebo group. In the second trial, the PANSS score decreased 14.5 points in the treatment group compared with 10.3 points in the placebo group. The most common adverse reactions were sleepiness/sedation and dry mouth.

The labeling for Caplyta includes a boxed warning noting that older patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. Caplyta is not approved for the treatment of patients with dementia-related psychosis.

According to Intra-Cellular Therapies, the company will launch Caplyta in the next few months.

For related information, see the American Journal of Psychiatry article “Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia.”

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Knowing Others in Treatment May Encourage People With Depression to Seek Care

People with depression may be more likely to seek treatment if they know of others with emotional problems or others who have sought treatment for emotional problems, suggests a study in Psychiatric Services in Advance.

“Our findings suggest that mere personal knowledge [of others with mental illness] may carry unique importance for treatment seeking beyond other well-studied social factors, such as social support and perceived stigma,” wrote Michelle M. Tran, M.S., of Palo Alto University and colleagues.

The findings were based on a follow-up survey of adults aged 18 years or older who participated in an international online depression screening study. A total of 239 participants who screened positive for major depression in the initial study agreed to answer follow-up questions, including whether they had ever sought professional help or treatment for depression; the number of people they knew with “emotional or mental problems” (within and outside of their family); and the number of people they knew who sought treatment for emotional or mental health problems (within and outside of their family). The participants also answered questions about their views toward depression, experiences with stigma, how supported they felt by others, and more.

The researchers found that participants who knew at least one person in their family with emotional or mental problems were nearly four times more likely to seek depression treatment than those who did not know of anyone in their family with such problems. Similarly, participants who knew at least one person with emotional or mental problems outside of their family were five times more likely to seek treatment for depression. Knowing at least one person within or outside of one’s family who received treatment for emotional or mental problems was also related to higher odds of treatment seeking by the participants, the researchers noted.

“Because our findings were correlational, it is unknown whether treatment seeking was the result of or a precursor to personal knowledge of others with mental health issues,” Tran and colleagues cautioned. “Future research should investigate whether this relationship is causal and if so, the direction of this relationship. If this relationship is found to be causal, encounter-based interventions can be developed for individuals at risk for depression, wherein they may meet others who have received treatment.”

For related information, see the Psychiatric Services article “Attitudes Toward Mental Health Help Seeking as Predictors of Future Help-Seeking Behavior and Use of Mental Health Treatments.”

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Get Ready for APA’s 2020 Election; Voting Begins January 2!

Voting members of APA will receive their ballots soon for APA’s 2020 election. Information about the candidates can be found on APA’s election website – members may also log in here and vote during the January 2-31 election period. Videos of the candidates for president-elect, treasurer, and trustee-at-large responding to questions posed by APA’s Election Committee will be posted on the APA election website by January 2, the day voting begins. Don’t let this opportunity to influence APA’s future pass you by—be sure to vote.

Heavy Alcohol Use Associated With Higher Risk for Suicide

Alcohol use may raise the short-term risk of suicide in patients who receive outpatient mental health treatment, according to a study published in General Hospital Psychiatry. The findings point to the importance of closely monitoring alcohol use in patients seeking psychiatric care.

Julie E. Richards, Ph.D., M.P.H., of the Kaiser Permanente Washington Health Research Institute and colleagues analyzed data from the electronic health records of more than 44,000 adults who had outpatient visits to a mental health professional between January 2010 and June 2015. All patients had received the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), which revealed their past-year level of alcohol consumption (how often they drank per week, and how many drinks they had when they drank). It also revealed their frequency of heavy drinking, defined as six or more drinks on one occasion, with response options of never, less than monthly, monthly, weekly, and daily or almost daily. The researchers then looked at the number of suicide attempts within 90 days of the visit in which the patients completed the AUDIT-C.

Of 59,382 patient visits, 371 were followed by a suicide attempt within 90 days. Patients who reported high-level alcohol use (based on average alcohol consumption per week) were 1.77 times more likely to attempt suicide than those who reported low-level alcohol use. Patients who reported daily or almost daily heavy drinking were 2.33 times more likely to attempt suicide than those who reported no heavy drinking.

“[T]he AUDIT-C can serve as a screening measure that might enhance health care organization practices to systematically [identify] suicide risk,” Richards and colleagues wrote. “Future research should examine the effects of integrating routine alcohol use screening and follow-up care … into care pathways designed to provide high-quality care for patients at risk of suicide, which some have argued is often a ‘missed opportunity’ in suicide prevention.”

For related information, see the American Journal of Psychiatry article “Predicting Suicide Attempts and Suicide Deaths Following Outpatient Visits Using Electronic Health Records” and the Psychiatric Services article “Heavy Alcohol Use Among Suicide Decedents: Differences in Risk Across Racial-Ethnic Groups.”

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More Green Space Around Schools May Reduce ADHD Symptoms, Study Finds

Increasing the amount of green space around schools may lower the odds that children will exhibit attention-deficit/hyperactivity disorder (ADHD) symptoms, according to a study published in JAMA Network Open.

“Accumulating evidence indicates that living in greener areas is associated with many beneficial health outcomes,” wrote Bo-Yi Yang, Ph.D., of Sun Yat-sen University in Guangzhou, China, and colleagues. “Given that attention is a critical prerequisite for learning, greenness in school settings may be of great public health significance.”

The authors conducted the population-based study between April 2012 and January 2013 in seven northeastern China cities. The analysis included 59,754 children (aged 2 to 17 years) from 94 schools, including kindergartens. Students who had lived at their current address for two years or longer were eligible for the study.

Participants’ parents and guardians completed the ADHD DSM-IV survey, rating the frequency that each ADHD symptom had occurred in the preceding six months on a four-point scale ranging from “never or rare” to “very often.” Children exhibiting six or more symptoms of either inattention or hyperactivity-impulsivity were defined as having ADHD symptoms.

Green space around schools and kindergartens was assessed using the normalized difference vegetation index (NDVI) and the soil-adjusted vegetation index (SAVI). Values ranged from negative one to one, with higher values indicating more green space (such as leaves and grasses), negative value representing bodies of water, and values close to 0 generally indicating barren areas, such as rock. Greenness estimates were based on satellite images taken in August 2010, “the greenest month in northeastern China,” according to the study.

Of the participants, 4.3%, or 2,566 students, had ADHD symptoms. The researchers found that a 0.1 unit increase in the NDVI or SAVI within 500 meters of a school or kindergarten was significantly associated with lower odds of ADHD symptoms. Associations persisted when adjusting for age, sex, parental education level, parental income level, type of home district, and dog ownership.

The authors offered several potential explanations for their findings. One hypothesis is that humans are innately attracted to nature, and the natural world may be beneficial to brain development. Green space may also encourage physical exercise and reduce the level of air pollutants, they noted.

The authors concluded that their findings “are relevant to policymakers and health care authorities for translating evidence into feasible and achievable targeted interventions (for example, planning for green spaces around schools and kindergartens) to mitigate the burden of ADHD in children.”

For related information, see the Psychiatric News article “Lingering in a Garden,” by Ezra E. H. Griffith, M.D.

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Early Psychosis Program in Washington State Shows Promise

People with first-episode psychosis (FEP) who received services through a coordinated specialty care program in Washington state called New Journeys experienced significant improvements in symptoms and quality of life after 12 months, according to a report in Psychiatric Services in Advance.

Coordinated specialty care involves a team of specialists who work with patients with FEP to create a treatment plan that may include psychotherapy, medication management, family education and support, case management, and work or education support. Coordinated specialty care was specifically designed for patients with FEP and was tested and found successful in the National Institute of Mental Health’s Recovery After Initial Schizophrenia Episode (RAISE) study.

The current study by Oladunni Oluwoye, Ph.D., of Washington State University and colleagues included 112 patients aged 18 to 40 diagnosed with psychosis. The patients and their clinicians answered questionnaires at intake and for the first 12 months of treatment about the patients’ anxiety and psychotic symptoms, quality of life, and substance use. Educational status was determined at intake and was reassessed monthly. Administrative data were used to assess use of emergency department, community psychiatric services, and public assistance 24 months before and 24 months after intake.

Patients in the program had significant decreases in symptoms of anxiety, psychotic experiences, and clinician-rated psychotic symptoms after 12 months. The patients reported better quality of life and were more likely to be attending school in the first 12 months of the program than at intake. They were less likely to visit the emergency department, use community psychiatric inpatient services, or use state-funded public assistance compared with 24 months before intake. There were no changes in patients’ substance use or employment status during their first year in the program.

“On the basis of the initial successes of New Journeys in addressing psychiatric symptoms and functional recovery, recent legislature has been passed promoting the rapid expansion of New Journeys in Washington State,” Oluwoye and colleagues wrote. “As more community mental health clinics adopt early intervention programs for FEP, additional efforts focusing on substance use behaviors, general health, peer engagement, and measurement-based care are needed.”

For related information, see the Psychiatric News article “Evidence Supporting Early Psychosis Treatment Grows as Programs Gain Ground in Communities.”

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Get Ready for APA’s 2020 Election; Voting Begins January 2!

Voting members of APA will receive their ballots soon for APA’s 2020 election. Information about the candidates can be found on APA’s election website – members may also log in here and vote during the January 2-31 election period. Videos of the candidates for president-elect, treasurer, and trustee-at-large responding to questions posed by APA’s Election Committee will be posted on the APA election website by January 2, the day voting begins. Don’t let this opportunity to influence APA’s future pass you by—be sure to vote.

Report Examines Changes in Suicide Patterns Among U.S. Army Personnel Over Time

Suicide rates among active-duty U.S. Army personnel increased during the wars in Vietnam, Afghanistan, and Iraq—reversing a trend dating back to the late-19th century in which suicides decreased among soldiers during wartime, according to a report in JAMA Network Open.

“As historical trends appear to show decreases in wartime suicide rates and as suicide is multifactorial, the findings of this study suggest that factors away from the battlefield may be associated with the change in suicide rates during active combat and among personnel in the U.S. Army,” wrote Jeffrey Allen Smith, Ph.D., of the University of Hawaii and colleagues.

Smith and colleagues analyzed data from a variety of government sources and published articles on suicide among active-duty personnel in the U.S. Army from 1840 to 2018. Starting in 1843, the overall trend in annual suicide rates among active-duty service members increased, with a peak rate of 118.3 per 100,000 in 1883. But after that, Smith and colleagues found that the rate of suicide decreased in three successive waves, corresponding to the end of the Spanish American War (1898), World War I (1914-1918), and World War II (1939-1945). The historically lowest suicide rate of 5 per 100,000 service members was recorded in 1944 and 1945.

In 1975, corresponding to the end of the Vietnam War, the suicide rate spiked to 18 per 100,000 service members. In 2012, during the wars in Iraq and Afghanistan, the suicide rate reached a peak at 29.7 per 100,000 service members. From 2008 to the present, the annual rate has not dropped below 20.2 per 100,000 service members.

The researchers suggested that some of the factors impacting the increased suicide rates could be the changes in the population comprising the U.S. Army over time and the length of the wars. They noted that the increased rates of suicide took place during the two longest wars in U.S. Army history: the wars in Vietnam and Afghanistan. “[T]hus, the question of how the length of wars is associated with suicide rates should be a topic for future research,” Smith and colleagues wrote.

In an editorial accompanying the study, David S. Jones, M.D., Ph.D., of Harvard Medical School noted that incorporating historical data can help improve theories about the cause of suicide among service members. “Even if the models that emerge from detailed historical analyses of military suicide are not used to guide campaigns against suicide today, the research will still provide valuable insight into the human conditions of military service during times of war and peace,” he wrote.

For related information, see the Psychiatric News article “With Changing Insights, Military Psychiatry Evolved Over Time.”

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Meta-Analysis Identifies Effective Doses and Dose Equivalents for 20 Antipsychotics

A meta-analysis published today in AJP in Advance reports the maximum effective dose for 20 antipsychotic medications, including both oral and long-acting injectable (LAI) formulations. The report also included the authors’ calculations of the dose equivalents of these 20 medications.

“The dose-response relationships of antipsychotic drugs for the acute treatment of schizophrenia are not well understood, but further defining them would be important for many reasons,” wrote Stefan Leucht, M.D., of the Technical University of Munich and colleagues. “Clinicians need to know the minimum effective doses and the maximum effective doses when they prescribe antipsychotics, and guidelines attempt to provide such information.”

Leucht and colleagues compiled data from 68 clinical studies that compared multiple doses of antipsychotics in people with acute schizophrenia symptoms. Using those data, they developed dose-response curves for the following medications: amisulpride, aripiprazole (oral and LAI), asenapine, brexpiprazole, cariprazine, clozapine, haloperidol, iloperidone, lurasidone, olanzapine (oral and LAI), paliperidone (oral and LAI), quetiapine, risperidone (oral and LAI), sertindole, and ziprasidone.

The dose-response graphs for many of the antipsychotics indicated that the optimal dose is likely less than the maximum approved dose. For example, the most effective doses of oral aripiprazole and risperidone were calculated at 11.5 mg/day and 6.3 mg/day, well below their top approved doses of 30 mg/day 16 mg/day, respectively. For such medications, raising the dose may not necessarily provide better symptom improvement, the authors noted.

For other medications such as lurasidone and oral olanzapine, the dose-response curve had not yet plateaued at the highest doses tested (160 mg/day and 15 mg/day respectively), suggesting the optimal dose may not have been identified yet. Leucht and colleagues believe that further clinical studies on dosing are warranted to see if these medications could be more effective.

“We stress that our results provide some guidance based on ‘average’ patients with chronic illness,” the authors concluded. “Individual dosing decisions should be guided by the properties of each drug (e.g., pharmacodynamic and pharmacokinetic properties, side effects), patient characteristics (e.g., age, illness stage, severity, physical comorbidities, and previously known individual effective doses), and concomitant treatments that could, by interaction, influence drug plasma levels.”

For more information, the authors provided an Excel spreadsheet with a dose conversion table and calculators.

To read more on this topic, see the American Journal of Psychiatry article, “Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.”

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Male Sex, Comorbid Psychiatric Conditions, Romantic Status Linked to Faster Progression to OCD

It takes an average of seven years for people who have some, but not all, symptoms of obsessive-compulsive disorder (subthreshold OCD) to develop full-blown OCD, according to a study in the Journal of Affective Disorders. The study also suggests that certain characteristics, such as male sex, the presence of other psychiatric conditions, and romantic status, may be associated with a faster transition from subthreshold OCD to OCD.

Emma M. Thompson, a Ph.D. candidate at Monash University in Australia, and colleagues examined data from 954 patients who were enrolled in treatment centers in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders between 2003 and 2009. The average age of the patients was 35 years; 358 were married, 520 were single, and 62 were divorced. Most were not working at the time of the assessment, and about half had a family history of OCD.

Every three years, consortium researchers interviewed and evaluated the patients using standardized assessment tools such as the Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV, among others. They found that males, patients with agoraphobia (fear of open or crowded places) without panic disorder, and patients with bipolar II disorder transitioned from subthreshold OCD to OCD in five years on average, compared with the overall average of seven years. Other characteristics associated with faster transition included greater severity of sexual/religious symptoms, lower severity of hoarding and general compulsive symptoms, and higher rates of current generalized anxiety disorder.

Patients whose symptoms were believed to be associated with their romantic status, such as being in love, starting an intimate relationship, or being about to wed, also transitioned from subthreshold OCD to OCD more quickly. The researchers wrote that it is difficult to speculate on the exact direction of the relationship between romantic status and transition to full-blown OCD. However, they noted that limerence, an involuntary state composed of intrusive romantic thoughts and concern over whether one’s romantic feelings are reciprocated, is associated with OCD.

“Rapid progression to the clinical level … may indicate the existence of a vulnerable population for whom the implementation of early interventions may be particularly relevant,” the researchers concluded.

For related information, see the American Journal of Psychiatry article “Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.”

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Cognition in Individuals With Psychotic Disorders Declined Over 20 Years, Study Finds

In a 20-year study, most cognitive functions in 445 individuals with psychotic disorders declined, according to a report published in JAMA Psychiatry.

“Compared with a matched control group, year-20 cognitive outcomes were poor in [participants with] psychotic disorders, especially for older participants,” wrote Anne-Kathrin J. Fett, Ph.D., of the University of London and colleagues. “These results provide the first comprehensive picture of long-term cognitive changes and associated clinical and functional outcomes in psychotic disorders.”

The participants were part of the Suffolk County Mental Health Project, a longitudinal study of patients with psychotic disorders recruited between 1989 and 1995 from 12 psychiatric inpatient units in Suffolk County, N.Y. To be included in the study, patients had to have had their first admission for a psychotic disorder within six months of recruitment and be between the ages of 15 and 60 years. Diagnoses included schizophrenia, schizoaffective disorder, psychotic bipolar disorder, major depressive disorder, and other psychoses.

The participants were evaluated two years after their initial hospitalization and again 20 years later. Researchers measured six cognitive domains: verbal knowledge, verbal declarative memory, visual declarative memory, attention and processing speed, abstraction-execution function, and verbal fluency.

Verbal fluency performance did not change over the 18 years, but verbal knowledge significantly increased. Performance declined significantly on all other tests, however. At both years two and 20, participants with schizophrenia spectrum disorders performed worse than those with other psychotic disorders.

“Older age at first cognitive assessment was associated with worse performance on the cognitive tests, except verbal knowledge and fluency,” the authors wrote. “These changes were similar in magnitude across all psychotic disorders. They were associated with worsening of negative symptoms and loss of gainful employment.”

If the results are successfully replicated, the authors concluded, “they will highlight the importance of studying cognitive and neural functioning in later phases of psychotic illness to develop further strategies for prevention of progressive deterioration.”

For related information, see the Psychiatric News article “Handgrip Linked to Cognition In Mood Disorders, Schizophrenia.”

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SNRIs May Be More Tolerable Than SSRIs for Some Youth With Anxiety, OCD

Youth who are taking antidepressants in the class of serotonin reuptake inhibitors (SSRIs) for anxiety or obsessive compulsive disorder (OCD) are more likely to experience side effects that cause them to discontinue the medication than those taking serotonin-norepinephrine inhibitors (SNRIs), according to a report in the Journal of the American Academy of Child and Adolescent Psychiatry.

SSRIs also appear to be more commonly associated with “activation syndrome”—a cluster of symptoms including restlessness, anxiety, and agitation.

Both classes of antidepressants are commonly prescribed for young people with anxiety and OCD, although SSRIs have been shown to be more effective. There are few data on specific side effects that may cause children and teens to stop taking these medications; however, this analysis suggests that SNRIs may be an option for youth who experience adverse effects with SSRIs, wrote lead author Jeffrey A. Mills, Ph.D., of the University of Cincinnati School of Business and Jeffrey Shawn, M.D., of Cincinnati Children’s Hospital.

The researchers analyzed data on adverse reactions to SSRIs and SNRIs in 18 studies involving more than 2,600 children and teenagers under the age of 18 treated for anxiety or OCD. The studies compared the two classes of drugs with placebo. The SSRIs that were studied were fluoxetine, fluvoxamine, sertraline, and paroxetine; the SNRIs were venlafaxine, atomoxetine, and duloxetine.

In the analysis looking at combined results for anxiety and OCD, the relative risks associated with sedation, abdominal pain, headache, and activation syndrome were greater for SSRIs than for SNRIs. The association with treatment discontinuation was also greater.

The researchers also noted that neither SSRIs nor SNRIs were more associated with suicide than placebo. This finding is in keeping with other research indicating that suicide among youth taking these medications is related to the underlying condition of depression and/or anxiety, not to medication effects.

For related information, see the Psychiatric News article, “Childhood Anxiety Can Be Treated—The Challenge Is to Recognize It.”

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Older Schizophrenia Patients Found Less Likely to Be Rehospitalized With LAI Antipsychotics

Individuals over age 60 with schizophrenia who were prescribed long-acting injectable (LAI) antipsychotics after being discharged from a hospital were significantly less likely to be rehospitalized within a year than those receiving oral antipsychotics, according to a report in The American Journal of Geriatric Psychiatry. Also, patients who did need to be admitted again had a longer time to rehospitalization.

LAI antipsychotics have been shown to improve adherence to medication in younger populations, which in turn improves overall outcomes. Yet evidence in older populations is lacking.

Risk factors for nonadherence in elderly patients with schizophrenia include psychosis, limited insight, adverse reactions, and stigma, wrote Ching-Hua Lin, M.D., Ph.D., of the Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Taiwan, and colleagues. These may be compounded by age-related factors, such as cognitive deficits that make it difficult to follow dosing instructions, or other medical problems.

The researchers analyzed data on 1,168 patients over age 60 with schizophrenia or schizoaffective disorder who were discharged between January 1, 2006, and December 31, 2017. Of these, 151 (12.9%) received LAI antipsychotic medication, and 1,017 (87 percent) received oral antipsychotic medication.

Eighty-one patients (53.6%) in the LAI group were rehospitalized within one year of discharge compared with 672 (66.1%) in the oral antipsychotic group, a statistically significant difference. The median time to rehospitalization for LAI patients was 257 days compared with 115 days for patients receiving oral antipsychotics.

Despite the positive results for LAIs compared with oral antipsychotics, the 53.6% rehospitalization rate remains frustratingly high. “In the future, further studies focusing on factors associated with risk of rehospitalization and effective interventions to prevent rehospitalization should be explored,” the researchers wrote.

For related information, see the Psychiatric News article “Clozapine, LAI Antipsychotics Found Best at Preventing Relapse.”

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Oxytocin Improves Empathy in Women With Borderline Personality Disorder

Oxytocin—a hormone that facilitates social bonding in animals—can improve empathy in women with borderline personality disorder (BPD), according to a study in Translational Psychiatry. Oxytocin was also associated with an increased desire to become emotionally close to someone.

“BPD patients often report problems establishing and maintaining stable relationships to significant others,” wrote Gregor Domes, Ph.D., of the University of Freiburg, Germany, and colleagues. “Their relationships are characterized by a pervasive fear of abandonment, anxiousness, mistrust, and conflicts, which can culminate in hostile and impulsive behavior.”

Domes and colleagues randomized 51 adult women with BPD and 51 age-matched women without BPD to receive either intranasal oxytocin or placebo 45 minutes prior to completing empathy assessments.

Women with BPD who received placebo scored significantly lower on tests measuring emotional empathy (feeling someone else’s pain), cognitive empathy (understanding someone else’s pain), and approach motivation than women in the control group taking placebo. Women with BPD were especially less responsive to positive emotions (pride, joy) than negative ones (sorrow, depression).

“It appears that BPD patients more easily empathize with people in aversive situations or in distress, while it is difficult for them to be empathic with people in positive social situations,” Domes and colleagues wrote. “This pattern is plausible, as negative emotions and situations are much more familiar to patients with BPD and thus negative emotions might be more easily accessible for BPD patients.”

Though oxytocin had no effect on cognitive empathy scores, the intranasal oxytocin was associated with significantly increased emotional empathy and approach motivation in both BPD and control participants. Further, the women with BPD reached a level of emotional empathy and approach motivation similar to that of the control group.

“These results could provide the starting point for designing controlled clinical trials, focusing on treatment efficiency using [oxytocin] as an add-on treatment to cognitive-behavioral psychotherapy in BPD,” Domes and colleagues concluded.

For related information, see the Psychiatric News article “Experts Offer Guidance for Treating Patients With Borderline Personality Disorder” and the Psychiatric Services article "Treatment of Borderline Personality Disorder: Is Supply Adequate to Meet Public Health Needs?"

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Integrating Brief Screen in ER May Better Identify Youth With Psychosis at Risk of Suicide

Almost half (48%) of children and adolescents with a psychotic disorder said they recently had suicidal thoughts or had in the past considered death by suicide when interviewed in the emergency department (ED) using a brief screening questionnaire, according to a report published this week in Psychiatric Services. Most of these youth did not report a chief complaint related to suicidal ideation or behavior when arriving at the ED.

Notably, half of the children and adolescents who screened positive for suicide using the Ask Suicide-Screening Questions (ASQ) screen were discharged from the ED, including 44% of those who reported having suicidal thoughts within the past few weeks.

“ASQ screening is imperative for the identification of youths at risk for suicide, but it needs to be paired with feasible follow-up intervention services,” wrote Jonathan DeVylder, Ph.D., of Fordham University and colleagues.

DeVylder and colleagues analyzed data on 87 children and adolescents aged 8 to 18 with a psychotic disorder who were screened for suicide risk in the ED using the ASQ at the Johns Hopkins Hospital pediatric ED. Youth were included if they had schizophrenia, schizoaffective disorder, major depressive disorder with psychotic features, or bipolar disorder with psychotic features, as recorded in the electronic health record.

The ASQ includes the following four yes/no questions: (1) In the past few weeks, have you wished you were dead?; (2) In the past few weeks, have you felt that you or your family would be better off if you were dead?; (3) In the past week, have you been having thoughts about killing yourself?; and (4) Have you ever tried to kill yourself? A positive response to any item is considered a positive screen.

The ASQ missed one young person with a suicide-related chief complaint. However, the authors noted that treatment as usual on the basis of chief complaints missed 26 young people that ASQ identified as at risk. The ASQ therefore increased detection of suicide risk almost threefold (2.63 times) relative to the chief complaint alone.

DeVylder and colleagues noted that the risk of suicide is especially pronounced shortly after the onset of psychosis, which tends to occur in adolescence or early adulthood. “This factor further compounds the elevated risk of suicide among adolescents after they are discharged from hospital-based psychiatric care,” they wrote.

For related information, see the Psychiatric News article “Surge in Suicide Prompts Call For Diagnostic Category.”

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Discontinuation of Buprenorphine Too Soon May Increase Risk of Adverse Outcomes

People who are treated with buprenorphine for more than 15 months appear to have superior clinical outcomes in the six months following buprenorphine discontinuation compared with those receiving the medication for shorter periods, according to a study published this week in AJP in Advance. However, there was no difference between the groups in rates of overdoses requiring medical treatment during this period.

“Although the study design cannot establish a causal relationship between longer retention and clinical outcomes, the results suggest that postdiscontinuation benefits may not begin to accrue until well after the six-month mark,” wrote Arthur Robin Williams, M.D., M.B.E., of the Columbia University Medical Center and colleagues. “[T]he results are consistent with a growing literature underscoring the protective effects of long-term pharmacotherapy for opioid use disorder as opposed to short-term use or brief detoxification.”

The researchers analyzed Medicaid claims data from 2013 to 2017 of patients who were 18 to 64 years old when they initiated buprenorphine treatment, were continuously retained on the treatment for at least six months, and maintained Medicaid enrollment for at least six months after discontinuing buprenorphine. The data included health information such as medication prescriptions and use of emergency services and inpatient and outpatient services.

The researchers separated these patients into four groups based on when they discontinued buprenorphine treatment (defined as a gap of more than 60 days after the last filled buprenorphine prescription): after 6 to 9 months (n=4,126), 9 to 12 months (n=2,440), 12 to 15 months (n=1,499), or 15 to 18 months (n=931).

The 15 to 18 months group had significantly lower rates of adverse events compared with the 6 to 9 months group, including fewer emergency department visits (41.2% compared with 48.6%), inpatient hospitalizations (11.3% compared with 13.9%), and opioid prescription claims (19.1% compared with 25.9%).

The rates of medically treated overdoses after discontinuation were about 5% for all groups, the authors wrote, “suggesting that overdose events in the subacute period following buprenorphine discontinuation remain common irrespective of treatment duration.” In fact, the six-month period following buprenorphine discontinuation was a “high-risk period for adverse events, especially among patients with comorbid mental illness,” they added.

They concluded, “Given high rates of early treatment discontinuation among patients who initiate buprenorphine treatment, often exceeding 50% within three to six months, greater efforts at the clinical and systems levels are needed to improve patient retention. Priority should be given to redesigning systems of care to emphasize chronic disease management models under collaborative care teams with emergency response capabilities for reaching patients who discontinue medication or disengage from care.”

For related information, see the Psychiatric Services study “Three-Year Retention in Buprenorphine Treatment for Opioid Use Disorder Among Privately Insured Adults.”

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Study Raises New Questions About How Best to Reduce Risk of Depression Recurrence

The return of depressive symptoms after treatment has ended is common in a number of patients with major depressive disorder (MDD). A study published today in JAMA Psychiatry found that patients who stopped taking antidepressants after recovery from chronic or recurrent depression had higher rates of recurrence than those who continued the medications. The difference in recurrence was observed regardless of whether the initial recovery was achieved with antidepressant monotherapy or a combination of antidepressants and cognitive-behavioral therapy (CBT).

“Maintenance of antidepressant medication treatment was associated with a reduced risk of depressive recurrence, but previous treatment with cognitive-behavioral therapy was not,” wrote Robert J. DeRubeis, Ph.D., of the University of Pennsylvania and colleagues.

The findings were based on data collected in the second of a two-phase study. In the first phase, the researchers compared outcomes of 452 patients with recurrent or chronic MDD randomly assigned to take antidepressants alone with those assigned to take antidepressant in combination with CBT. Patients who recovered from MDD (defined as 26 consecutive weeks without relapse) were invited to participate in phase 2 of the trial, in which they were randomized to continue antidepressant treatment or withdrawn from antidepressants over several weeks. (Patients who had received combination therapy treatment during phase 1 ended their course of CBT treatment when phase 2 began.) A total of 292 patients who participated in phase 1 of the study consented to participate in phase 2. These patients were then followed for three years.

“Antidepressant medication maintenance was associated with lower rates of recurrence compared with medication withdrawal regardless of whether patients had achieved recovery with monotherapy treatment [antidepressant only] in phase 1 (48.5% with medication maintained vs 74.8%) … or combination therapy treatment (48.5% with medication maintained vs 76.7% with medication withdrawn),” DeRubeis and colleagues wrote. “No evidence was found that the provision of CBT during acute/continuation treatment [in phase 1] provided protection against subsequent recurrence. … If anything, the initial advantage of the combination therapy treatment that was observed in phase 1 appeared to decrease during the phase 2 follow-up period.”

Psychiatrist Marlene P. Freeman, M.D., the Abra Prentice Foundation Chair in Women’s Mental Health at Massachusetts General Hospital, summarized several takeaways from the findings in an accompanying editorial. “This study clearly underscores the benefit of maintenance antidepressant treatment for this population and is in line with the body of maintenance studies of antidepressant medications, in which randomized studies consistently report that continuation of the medication on which remission occurred provides protection against recurrence at higher rates than placebo. This said, as a field we need to address the challenges associated with maintenance use of antidepressant medications.”

The study leaves several important questions unanswered, she noted: “It is not known how the combination therapy group who recovered in phase 1 would have fared if randomized to continue or discontinue treatment with CBT. We also do not know if and how much better the combination therapy would have been in preventing relapse in phase 2, which is important because relapse rates were relatively high, even with medication maintenance.”

For related information, see the Psychiatric News article “Tips for Recognizing, Treating Symptoms of SSRI Discontinuation,” by Madhukar H. Trivedi, M.D., and Manish K. Jha, M.B.B.S.

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Psychiatrist Offers Tips for Evaluating, Treating Sleep Problems in Patients

Treating psychiatric patients for sleep disturbances can lead to improvements in their quality of life and mental health, but few mental health professionals receive thorough training on how best to assess common sleep complaints. So wrote John W. Winkelman, M.D., Ph.D., a professor of psychiatry at Harvard Medical School and chief of the Sleep Disorders Clinical Research Program at Massachusetts General Hospital, in an article in JAMA Psychiatry.

“Sleep is a powerful biological drive but, paradoxically, is easily perturbed by a variety of processes. Psychiatric illnesses are one such influence, and … many psychiatric medications either interfere with sleep or can produce hypersomnia,” he wrote. To address sleep disturbances, Winkelman advised mental health professionals to first determine their patient’s chief sleep complaint followed by assessments of psychiatric, medical, neurological, and sleep-specific conditions.

“Treatment of sleep complaints is usually directed toward specific reversible causes when present (e.g., pain, mood or anxiety disorders, restless legs syndrome, sleep apnea, nocturia, thyroid disease) and proceeds to more generic treatments (cognitive-behavioral therapy [CBT], hypnotic medications, stimulants) if the initial approaches are not effective,” Winkelman wrote. “However, given the bidirectional relationship of sleep disturbance and psychiatric illness, such generic treatments may provide independent value for both the sleep disorder and psychiatric illness and should be considered for concomitant initial treatment.”

Winkelman concluded the article with recommendations for several treatment options for patients with insomnia—including cognitive-behavioral therapy for insomnia (CBT-I), recognized as a first-line therapy for patients with this disorder; and pharmacological therapies, including hypnotics for short-term use, and for long-term use, sedating antidepressants (trazodone, mirtazapine, doxepin), anticonvulsants (gabapentin), orexin antagonists (suvorexant), and melatonin agonists.

“Sleep disturbance is very common in patients with psychiatric illnesses, and thorough evaluation often leads to remediable causes. Treatment can improve both immediate quality of life and the course of underlying psychiatric illness,” he wrote.

For related information, see the Psychiatric News article “Overlapping Symptoms Complicate Diagnosis, Treatment of Psychiatric and Sleep Disorders.”

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