Combining Aripiprazole, Venlafaxine Reduces Depressive Symptoms in Older Adults

Adding a low dose of the antipsychotic aripiprazole to the antidepressant regimen of older adults with treatment-resistant depression may help them achieve and sustain remission, according to a study published yesterday in the Lancet.

Previous studies show that more than half of older adults with major depressive disorder fail to respond to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). In the current study, Charles Reynolds, M.D. (pictured left), a professor of geriatric psychiatry at the University of Pittsburgh School of Medicine, and his colleagues tested the effectiveness and safety of aripiprazole as an adjunctive therapy to venlafaxine in 468 adults aged 60 and over with no history of cognitive deficits.

Each study participant received an extended-release formulation of venlafaxine—ranging from 150 mg per day to 300 mg per day—for 12 weeks. Of the 181 patients whose symptoms did not remit after 12 weeks of treatment, 91 were randomly assigned to receive venlafaxine for another 12 weeks with the addition of 10 mg to 15 mg of aripiprazole and 90 received placebo in addition to venlafaxine each day. Remission was defined as a Montgomery Asberg Depression Rating Scale score of 10 or less (and at least 2 points below the score at the start of the randomized phase) at both of the final two consecutive visits.

The results showed that combined venlafaxine and aripiprazole therapy led to remission of depressive symptoms in 44% of treatment-resistant patients compared with 29% of participants who received venlafaxine and placebo.

Akathisia and Parkinsonism were the most common adverse events reported by participants in the aripiprazole adjunctive therapy group, occurring respectively in 26% and 17% of those patients. No differences were reported between groups in changes in percentage of body fat, or in total cholesterol, HDL, LDL, triglycerides, glucose, or insulin concentrations.

“Our results showed that aripiprazole is moderately effective in older adults with treatment-resistant depression,” the authors wrote. “Clinicians prescribing this medication should be aware of its propensity to cause akathisia and Parkinsonism. However, the potential benefits of remission from depression and greater reductions in suicidal ideation outweigh these usually mild adverse events.”

To read more about treating older adults with depression, see the Psychiatric News article “Older Adults Are More Likely to Receive Prescriptions for Depression, Anxiety.”

Human Rights Expert to Be Keynote Speaker at APA’s Meeting in NYC

Adeyinka M. Akinsulure-Smith, Ph.D., is a licensed psychologist from Sierra Leone who has participated in human rights investigations in Sierra Leone, worked with war victims from the African diaspora and survivors of torture, and served as an expert on gender crimes and posttraumatic stress disorder in a case before the International Criminal Court. She will discuss her work and experiences on Thursday, October 8, at IPS:The Mental Health Services Conference, which is being held at the Sheraton New York Times Square Hotel. Learn more about the meeting and register now.

(Top image courtesy of University of Pittsburgh School of Medicine)

Decision Tool Helps Patients Feel More Satisfied With Antidepressant Selection

A tool to help patients with depression make informed decisions about appropriate antidepressants improves the antidepressant decision-making process without extending the length of primary care visits, according to a report in JAMA Internal Medicine.

The tool, developed by researchers at the Mayo Clinic in Rochester, Minn., is called Depression Medication Choice (DMC). DMC consists of a series of cards that present general information about antidepressant efficacy and highlight various features of antidepressants—for instance, effects on sleep, sexual issues, and weight gain. The cards are used by the patient with the clinician during the primary care visit.

Primary care practices in 10 rural, suburban, and urban areas (117 clinicians and 301 patients) across Minnesota and Wisconsin were randomly assigned to treat depression with or without use of the DMC decision aid from December 2011 to November 2013.

After the encounters with their clinicians, patients in the decision aid arm reported significantly higher comfort with the decision and were more knowledgeable and satisfied compared with patients in the control arm. It also improved clinicians’ decisional comfort and satisfaction, without extending the time of the office visit.

However, there was no observed difference between the two groups in control of depression symptoms (mean Patient Health Questionnaire for depression [PHQ-9] score), remission rate (PHQ-9 score less than 5), or responsiveness (greater than 50% PHQ-9 improvement) at three and six months, or in medication use or adherence.

“Depression Medication Choice is a novel and efficient shared-decision-making tool,” the authors stated. “It effectively helps patients with moderate to severe depression and their primary care clinicians engage in collaborative deliberation by using evidence about the comparative effectiveness of antidepressants.”

For related information, see the Psychiatric News article “Risk-Benefit Analyses in Medication Decision Making.

Human Rights Expert to Be Keynote Speaker at APA’s Meeting in NYC

Adeyinka M. Akinsulure-Smith, Ph.D., is a licensed psychologist from Sierra Leone who has participated in human rights investigations in Sierra Leone, worked with war victims from the African diaspora and survivors of torture, and served as an expert on gender crimes and posttraumatic stress disorder in a case before the International Criminal Court. She will discuss her work and experiences on Thursday, October 8, at IPS:The Mental Health Services Conference, which is being held at the Sheraton New York Times Square Hotel. Learn more about the meeting and register now.

(Top image: Stuart Jenner/Shutterstock)

Addiction Society Publishes New Practice Guideline on Opioid Use Disorders

The American Society of Addiction Medicine (ASAM) has released a national practice guideline on the use of medications to treat opioid use disorders. The guideline was created in response to the rapid increase in recent years in the number of people misusing and overdosing on morphine and other opioids (both prescription and non-prescription).

The guideline was developed by a multidisciplinary committee consisting of specialists in addiction medicine and other fields to assist physicians in evaluating, managing, and treating patients with opioid use disorder. The guideline provides specific and evidence-based guidance on selecting the best treatments for opioid use disorders. These include the opioid agonist methadone, the partial agonist buprenorphine, the opioid antagonist naltrexone, and the opioid blocker naloxone. The guideline also discusses the importance of pairing any pharmacological treatment of opioid use disorder with psychosocial treatment and includes recommendations for patient populations with special needs, such as those with comorbid psychiatric disorders.

“The available evidence indicates that use of medications in addition to psychosocial treatments is supported for the treatment of opioid use disorder,” the authors of the guideline reported. “Prescription of the indicated medications is not completely simple, and skill and time are required to ensure that treatment is effective and diversion of the abusable medications is not occurring. This Guideline describes aspects of treatment that should be attended to be effective.”

The APA’s Practice Guideline on Substance Use Disorders also includes a section on managing opioid use disorders.

To read about the current legislative efforts to control opioid abuse, see the Psychiatric News article “House Members Consider Best Options for Treatment, Prevention of Opioid Abuse.”

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Intervention May Reduce Risk of Anxiety in Children With Anxious Parents

A family-based cognitive-behavioral intervention aimed at families in which at least one parent had an anxiety disorder reduced the likelihood that children in the family developed anxiety disorders, according to a study published today in AJP in Advance.

For the study, Golda Ginsburg, Ph.D., a professor of psychiatry at the University of Connecticut Health Center, and colleagues randomly assigned 136 families to either the eight-week Coping and Promoting Strength program or a control condition using an informational pamphlet. All participating families had at least one parent who met DSM-IV-TR criteria for an anxiety disorder and one child aged 6 to 13 without an anxiety disorder.

As part of the intervention program, each family met individually with a trained therapist for 60 minutes a week for eight weeks. The families were taught how to identify the signs of anxiety and how to reduce anxiety, problem solving, parenting strategies, and more. Participants in the information-monitoring group received a 36-page pamphlet containing information about anxiety disorders and associated treatments. Anxiety was assessed before the trial began, at the end of the intervention (or eight weeks after randomization), and at follow-ups six and 12 months later.

Children in the intervention group had lower symptom scores after finishing the program. Just three children (5%) in the intervention group met criteria for an anxiety disorder by the end of the 12-month follow-up period compared with 19 children (31%) in the information-monitoring group. At the one-year follow-up, youth in the control group also had higher anxiety symptoms ratings than those in the intervention group.

“[A]mong youth who received the intervention, those with high baseline anxiety symptom severity levels showed greater reductions in severity than those with low baseline levels, which suggests that the intervention is particularly helpful for youth with elevated anxiety symptoms,” the study authors wrote.

While the study authors noted that the work needs to be replicated in a larger and more demographically diverse cohort, it may represent a step forward in efforts to reduce the number of children and adolescents with anxiety disorders.

“Prevention is always better than providing intervention after a disorder has been identified,” child psychiatrist Paramjit Joshi, M.D., division chief of psychiatry and behavioral medicine at Children’s National Medical Center in Washington, D.C., told Psychiatric News. “In that sense I think this is an important study and has clinical applicability.”

For related information, see the Psychiatric News article “Transmission of Anxious Behaviors to Offspring Has More to Do With Environment Than Genes.”

Human Rights Expert to Be Keynote Speaker at APA’s Meeting in NYC

Adeyinka M. Akinsulure-Smith, Ph.D., is a licensed psychologist from Sierra Leone who has participated in human rights investigations in Sierra Leone, worked with war victims from the African diaspora and survivors of torture, and served as an expert on gender crimes and posttraumatic stress disorder in a case before the International Criminal Court. She will discuss her work and experiences on Thursday, October 8, at IPS:The Mental Health Services Conference, which is being held at the Sheraton New York Times Square Hotel. Learn more about the meeting and register now.

(Top image: hartphotography/Shutterstock)

Drug Combination Found to Reduce Agitation in Patients With Alzheimer's

A combination of dextromethorphan (a cough suppressant) and quinidine (an antiarrhythmic medication) appears to be clinically efficacious for agitation in patients with Alzheimer’s disease and to be generally well tolerated, according to a report published online Tuesday in JAMA Psychiatry.

Researchers from multiple institutions conducted a two-stage trial. In stage 1, 220 patients with probable Alzheimer’s disease (based on 2011 National Institute on Aging–Alzheimer Association criteria) and clinically significant agitation were randomized in a 3-to-4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127) for five weeks. In stage 2, the patients who had originally received dextromethorphan-quinidine continued to take the medication, while those receiving placebo were stratified by response and re-randomized in a 1-to-1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60) for an additional five weeks.

The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain.

Analysis combining both stages showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine versus placebo. In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. In stage 2, NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. Serious adverse events occurred in 7.9% of patients administered dextromethorphan-quinidine versus 4.7% administered placebo. Dextromethorphan-quinidine was not associated with cognitive impairment, sedation, or clinically significant QTc prolongation.

“Dextromethorphan, the neurologically active component of the dextromethorphan-quinidine combination, has activity at receptors involved in modulating glutamate, serotonin, norepinephrine, and potentially other neurotransmitters, although the exact mechanism of action responsible for the reduction of dementia-associated agitation is not known,” the researchers stated.

As described in the recent Psychiatric News article “Combination of Dextromethorphan, Quinidine Reduces Agitation in Alzheimer’s Patients,” details of this study were presented at the 2015 Alzheimer’s Association International Conference in Washington, D.C., in July.

(Image: IgorGolovniov/Shutterstock)

Patients With Severe Depression May Benefit Equally from CBT, Antidepressants

Previous studies have shown psychotherapies, in particular cognitive-behavioral therapy (CBT), to be just as effective as pharmacotherapies in treating mild to moderate symptoms of depression. But, less is known about the relative effectiveness of psychotherapy compared with pharmacotherapy in populations with severe depression, and current guidelines recommend that antidepressant medications are used for the treatment of severe depression in the context of major depressive disorder. Now, a meta-analysis published today in JAMA Psychiatry suggests that only a modest difference is seen in the effectiveness between the two therapies among patients who are severely depressed.

Researchers from the VU University Amsterdam analyzed primary data submitted by the authors of 16 randomized, controlled trials in which CBT was compared with pharmacotherapy among outpatients with a primary diagnosis of a depressive disorder (major depressive disorder or dysthymia). Main outcome measures included improvements in scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI), as well as the rates of response and remission.

Based on their analysis, the researchers identified a modest (less than 1 point) main effect of antidepressant pharmacotherapy over CBT on the HAM-D and a nonsignificant trend on the BDI, but no significant differences in rates of response (defined as 50% reduction in scores on post-test HAM-D) or remission. Additional analysis indicated that baseline depression severity does not moderate reductions in depressive symptoms between CBT and antidepressant medications.

The authors wrote that while their analysis “shows that pharmacotherapy provides minor improvement in the treatment of depression relative to CBT in terms of the continuous measures, there is no indication that differences between the modalities were moderated by the degree of baseline depression severity. Therefore, the data are insufficient to recommend [antidepressant medications] over CBT in outpatients based on baseline severity alone,” the authors wrote. “More research is needed to examine whether other demographic and clinical characteristics moderate the differential response between CBT and [antidepressant medications].”

A senior author on this paper previously investigated treatment response differences among racial and ethnic groups, as reported in the Psychiatric Services article "The Effects of Psychotherapy on Depression Among Racial-Ethnic Minority Groups: A Metaregression Analysis."

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Providers Found to Regularly Follow Clinical Practice Guidelines When Diagnosing ADHD

While the uptick in the percentage of U.S. children diagnosed with attention-deficit/hperactivity disorder (ADHD) over the past decade has led some to question the validity of these diagnoses, a recent CDC report suggests that providers have regularly followed clinical practice guidelines when diagnosing the disorder.

The findings are based on data collected during a follow-up survey to the 2011–2012 National Survey of Children’s Health (NSCH)—a nationally representative telephone survey of households with children from birth to age 17 in the United States. For the follow-up, parents with children aged 2 to 15 who had been told by a physician or other health care provider that their child had ADHD were recontacted and asked questions about the steps that led to the diagnosis. A total of 2,976 ADHD interviews were completed from January to June 2014.

To evaluate children for ADHD, the American Academy of Pediatrics (AAP) recommends that providers perform a diagnostic evaluation using the Diagnostic and Statistical Manual of Mental Disorders and assess the extent of the child’s impairment and the pervasiveness of the impairment across multiple settings. AAP also recommends that information on the child's behavior be obtained from multiple people, including parents, teachers, and other child care providers.

The results of the follow-up survey revealed that the median age at ADHD diagnosis was 7 years, and about 1 in 3 children (30.7%) was diagnosed before age 6. Approximately one-half of children with ADHD were diagnosed first by a primary care provider, such as a pediatrician (39%) or general health physician (14.1%). Approximately 1 in 4 children diagnosed with ADHD before age 6 (23.7%) was first diagnosed by a psychiatrist; when diagnosed at an older age, children were less likely to be diagnosed by a psychiatrist (15.6%).

Parents were also asked about the methods used by the diagnosing provider to assess their child for ADHD. Consistent with best practices, behavior rating scales or checklists were used for 89.9% of children assessed for ADHD. Additionally, more than three-quarters diagnosed before age 6 and nearly two-thirds diagnosed at ages 6 and over had undergone neuropsychological testing. For the majority of children (81.9%), at least one adult outside the family was involved in the diagnostic process.

“Describing the diagnostic experiences of a representative sample of U.S. children with ADHD is an important step toward understanding how children are diagnosed with ADHD in the United States and helps to inform efforts that seek to ensure that best practices are used in the evaluation and diagnosis of the disorder,” the study authors wrote.

For related information, see the Psychiatric News article “Education Policies May Influence ADHD Diagnoses.”

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FDA Approves Vraylar for Treatment of Schizophrenia and Bipolar Disorder

The Food and Drug Administration (FDA) last week approved Vraylar (cariprazine), a dopamine D2/D3 receptor partial agonist, as a treatment for schizophrenia and bipolar disorder in adults.

The approval was based on a set of six controlled clinical trials that included over 2,700 adults with bipolar disorder or schizophrenia. Vraylar was shown to reduce the symptoms of both disorders compared with placebo, and was fairly well tolerated, with the most commonly reported adverse reactions being extrapyramidal symptoms and restlessness (akathisia).

Vraylar is one of the first FDA-approved antipsychotics that has demonstrated efficacy in alleviating negative symptoms of schizophrenia such as a lack of motivation or desire.

It is important to have a variety of treatment options available to patients with mental illnesses so that treatment plans can be tailored to meet a patient's individual needs,” Mitchell Mathis, director of the Division of Psychiatry Products in the FDA's Centre for Drug Evaluation and Research, said in an FDA release.

Gedeon Richter Plc. had previously submitted an approval request for this drug in 2013 that was turned down by the FDA, with the agency acknowledging the drug’s effectiveness but requesting more data, particularly information on optimal dosing for this oral, once-daily drug.

According to a release by Gedeon Richter and Allergan, the recommended dose range for Vraylar for the acute treatment of adult patients with manic or mixed episodes associated with bipolar I disorder is 3 to 6 mg/day and 1.5 to 6 mg/day for the treatment of schizophrenia in adults.

To learn more about cariprazine, see the Psychiatric News article “As FDA Decision Nears, Cariprazine Collects More Proof of Efficacy.

(Image: Hurst Photo/Shutterstock)

Study Finds No Association Between Childhood Adversity and Course of Psychotic Illness

There does not appear to be any significant association between a history of childhood adversity and the course of psychotic illness during the first year after presentation to mental health services, according to a report published online in Schizophrenia Bulletin. However, childhood adversity was associated with several outcomes that the authors of the study suggest could impact service use and social functioning among psychosis patients.

Researchers at King’s College London investigated associations between childhood adversity and one-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis.

A total of 71% of patients reported exposure to at least one type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). Despite the high prevalence of childhood adversity in the sample of patients, the researchers found no evidence that a history of adversity impacted either remission from psychotic symptoms or global functioning scores at one-year follow-up. There was no robust evidence of a dose-response effect for exposure to multiple adverse experiences on clinical course of psychosis, symptomatic remission, or global clinical functioning over one-year follow-up.

Psychosis patients who reported a history of physical abuse were almost three times more likely to be single at follow-up compared with patients who did not report this type of adversity. Moreover, there was evidence of an association between parental separation in childhood and a longer admission to a psychiatric ward during one-year follow-up, with cases reporting such adversity being approximately twice as likely to have longer hospital stays compared with those without such a history. Evidence of a two-fold increased odds of noncompliance with medications was also found among those patients who reported childhood exposure to parental separation or disrupted family arrangements, though the latter association fell just short of statistical significance.

“Given the high prevalence of childhood adversities reported by first-presentation psychosis cases in this sample, routine assessment of adversity history and psychotherapies focused on adverse childhood experiences should be considered by services providing treatment to psychosis patients,” the researchers wrote.

For related information, see the Psychiatric News article “Link Found Between Childhood Infections, Later Psychosis.”

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Reanalysis of JAACAP Study on Paroxetine Sparks Controversy

A reanalysis of data from a 2001 study that concluded paroxetine to be generally well tolerated and effective for treating major depression in adolescents has raised questions over the safety and effectiveness of the drug in this patient population, according to a paper published Wednesday in the BMJ.

The original study, published in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), describes an eight week, double-blind randomized control trial that compared the safety and effectiveness of paroxetine (20 mg to 40 mg) and imipramine (gradual upward titration to 200 mg to 300 mg) with placebo in 275 adolescents aged 12 to 18 with major depression.

In the paper, Martin Keller, M.D., of Brown University and colleagues reported that after eight weeks, those in the paroxetine group demonstrated significantly greater improvement compared with placebo on the Hamilton Rating Scale for Depression (HAM-D) total score, HAM-D depressed mood item, depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version depressed mood item, and Clinical Global Impression score.

For the BMJ study, Jon Jureidini, M.B.B.S., of the University of Adelaide, and colleagues reanalyzed the data from the 2001 study, including a review of primary data from the original trial supplied by GlaxoSmithKline. (The reanalysis was part of an initiative called RIAT [Restoring Invisible and Abandoned Trials], which calls on “funders and investigators of abandoned [unpublished] or misreported trials to publish undisclosed outcomes or correct misleading publications,” according to the study authors.)

Based on the reanalysis, the authors reported, “The efficacy of paroxetine and imipramine was not significantly different from placebo for any prespecified primary or secondary outcome.” The authors also described “clinically significant increases in harms, including suicidal ideation and behavior and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group.”

“That one can do better reanalyzing adverse-event data using refinements in approach that have accrued in the 15 years since a study’s publication is unsurprising and not a valid critique of our study as performed and presented,” Keller and his colleagues noted in a letter in response to the BMJ article. The authors concluded, “In summary, to describe our trial as 'misreported' is pejorative and wrong, both from consideration of best research practices at the time, and in terms of a retrospective from the standpoint of current best practices.

“This new reanalysis has sparked a healthy discussion over the value of open access to clinical trial data, the importance of following protocol specified analyses, and the risks of confirmation bias, which is a tendency to search for information that confirms the investigator's preconceptions,” Mark Olfson, M.D., M.P.H., a professor of psychiatry at Columbia University Medical Center who was not involved with either study, told Psychiatric News. “However, the new reanalyses does not alter the totality of clinical trial evidence that continues to support the safety and efficacy of SSRIs for adolescent depression.”

Daniel Pine, M.D., chief of NIMH's Section on Development and Affective Neuroscience, added, “We have known for some time that antidepressant medications have both significant benefits for some children as well as significant risks for other children. This new analysis really does nothing to change this knowledge, and provides no new insights into what we have known about these medications for the past few years.”

“AACAP supports transparency in clinical trial reporting and welcomes the RIAT initiative, which enables publicly available primary data to be reanalyzed and published as new, potentially revised reports,” Paramjit T. Joshi, M.D., President of the American Academy of Child and Adolescent Psychiatry, told Psychiatric News. “JAACAP is a forum for scientific reporting and scholarly discussion. The scientific process builds on itself over time through a cycle of new research, analysis, and ongoing dialog. This process stimulates debate and moves the field forward toward a better understanding of critical issues.”

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FDA Modifies Clozapine Prescribing and Monitoring Requirements

Yesterday, the Food and Drug Administration announced that it is making changes to the requirements for monitoring, prescribing, and dispensing clozapine, a medication intended to treat symptoms of schizophrenia and recurrent suicidal behavior in patients with schizophrenia and schizoaffective disorder. The modifications are part of an effort to address continuing safety concerns over the increased risk of neutropenia—a serious blood condition characterized by dangerously low numbers of neutrophils (white blood cells that help fight infections)—in patients being treated with clozapine.

As part of the new changes, the FDA has clarified and enhanced the prescribing information for clozapine that explains how to monitor patients for neutropenia and manage clozapine treatment. In addition, the agency announced a new, shared risk evaluation and mitigation strategy (REMS) called the Clozapine REMS Program to improve the monitoring and management of patients with severe neutropenia. This program, which will require prescribers, pharmacies, and patients to enroll in a single centralized program, replaces the six existing clozapine registries maintained by individual clozapine manufacturers.

Neutropenia will now be monitored by the absolute neutrophil count (ANC) only, rather than in conjunction with the white blood cell count. The requirements for ANC are also being modified so that patients will be able to continue on clozapine treatment with a lower ANC—a change that will allow continued treatment for a greater number of patients. Patients with benign ethnic neutropenia, who previously were not eligible for clozapine treatment, will now also be able to receive the medicine.

“The revised prescribing information facilitates prescribers’ ability to make individualized treatment decisions if they determine that the risk of psychiatric illness is greater than the risk of recurrent severe neutropenia, especially in patients for whom clozapine may be the antipsychotic of last resort,” the FDA noted in a statement announcing the changes.

Patients who are currently treated with clozapine will be automatically transferred to the Clozapine REMS Program. In order to prescribe and dispense clozapine, prescribers and pharmacies will be required to be certified in the Clozapine REMS Program according to a specific transition schedule starting October 12, 2015.

For related information, see the Psychiatric News article “Why Won't Clinicians Use Clozapine Despite Proven Superiority?”

Thomas Insel, M.D., Resigns as Director of NIMH

After serving 13 years as director of the National Institute of Mental Health (NIMH), Thomas Insel, M.D., will step down effective November 1. Insel first worked at NIMH from 1980 to 1994 in the Division of Intramural Research and then returned as director in 2002. 

“Dr. Insel provided excellent leadership of NIMH during this critical time in mental health research,” said APA President Renée Binder, M.D. “During his tenure, NIMH has spearheaded the BRAIN initiative [Brain Research through Advancing Innovative Neurotechnologies] and other major research efforts. We look forward to assisting the Obama administration as it works to identify the next director.”

Insel has overseen NIMH during a period of remarkable advances in the understanding of the brain and the genetic and neurobiological underpinnings of mental illness, as well as in clinical research to improve treatment of mental illness. His leadership has helped to advance an appreciation of mental disorders as complex illnesses involving genes, interrelated neurocircuitry, environment, and behavior. He has also been instrumental in the movement toward early identification of mental illness, recognizing that many of the most serious disorders begin well before they typically come to clinical attention. 

In a statement posted on the website of the National Institutes of Health (NIH), NIH Director Francis Collins, M.D., Ph.D., said that under Insel’s leadership, NIMH has “nurtured a culture of science that puts the needs of patients with serious mental illness at the center of its efforts.” 

In addition to the BRAIN initiative, among other major initiatives in which he has been involved are the Psychiatric Genomics Consortium, which involves over 500 researchers in over 80 institutions across 25 countries; the Army STARRS (Study to Assess Risk and Resilience in Servicemembers) project, an unprecedented partnership between NIH and the Department of Defense that is the largest study of mental health risk and resilience ever conducted among military personnel; the National Database for Autism Research (NDAR), considered the most significant repository for autism-related data; and RAISE (Recovery After an Initial Schizophrenia Effort), an NIMH research effort that seeks to change the trajectory and prognosis of schizophrenia through coordinated and aggressive early treatment. 

Collins noted that Insel is planning to join the Google Life Sciences (GLS) team at Alphabet (formerly Google) to lead a new effort that will focus on mental health. The GLS mission is to create technology for earlier detection, better prevention, and more effective management of serious health conditions. In his new role, Insel will be exploring this approach for a wide spectrum of issues in mental health, Collins said. 

“We congratulate Dr. Insel on his service to NIMH and the nation,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “His new opportunity at Alphabet will increase mental health field advances well into the future, and we at APA look forward to continuing to work with him.

During the search for a successor, Bruce Cuthbert, Ph.D., will serve as acting director. 

Low Vitamin D Levels May Accelerate Cognitive Decline in Older Adults

Older adults with vitamin D deficiencies showed more rapid cognitive decline than those with adequate vitamin D levels, reports a study published today in JAMA Neurology.

To assess associations between vitamin D status and trajectories of change in subdomains of cognitive function, researchers from Rutgers University and the University of California, Davis, monitored 382 people (average age of 75) for around five years. The participants were a diverse group, both in ethnicity and cognitive status at baseline.

Around 60% of all the study participants had low vitamin D levels in their blood, including 70% of the African-American and Hispanic participants. Those who were either vitamin D deficient (less than 12 ng/mL serum levels) or insufficient (12 to 20 ng/mL) had faster declines (around 2 to 3 times faster) in episodic memory and executive function than those with adequate vitamin D levels, independent of other potential risk factors, the authors reported. Vitamin D status was not significantly associated with declines in semantic memory or visuospatial ability, however. When removing those participants who had dementia at the start of the study, the correlation between vitamin D and cognitive decline was still present.

“Given that [vitamin D] insufficiency is medically correctable, well-designed clinical trials that emphasize enrollment of individuals of nonwhite race/ethnicity with hypovitaminosis D could be useful for testing the effect of [vitamin D] replacement on dementia prevention,” the study authors wrote.

While there have not been any clinical studies demonstrating that vitamin D supplementation can improve memory, the study authors suggested older patients should consult their physicians about taking vitamin D.

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Delirium and Hypovitaminosis D: Neuroimaging Findings.”

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Leading Mental Health Organizations Join Campaign Against Kenneth Cole Billboard

Twenty-one medical and advocacy organizations have joined in APA’s campaign urging fashion designer Kenneth Cole to remove a billboard message in Manhattan that creates the misleading impression that people who suffer from mental illness are violent. The organizations represent the nation's psychiatrists, psychologists, social workers, and patients and their families.  

Since the billboard message was posted a few weeks ago, APA has been conducting an intensive information campaign to set the record straight about the link between mental illness and violence and to urge Mr. Cole to remove the stigmatizing message.

“You are absolutely correct that many Americans with mental health issues don’t get the help they need,” the organizations wrote in a letter to Mr. Cole today. “Only 38 percent of adults with mental illness receive treatment. The right answer is to get people treatment, not to marginalize them. Stigma about mental health is one of the biggest barriers preventing people from seeking care, and your billboard unfortunately adds to that stigma.”

Earlier this week, APA Communications Chief Jason Young was told by a spokesperson for Mr. Cole’s company that the billboard message would be replaced only “as normally scheduled.”

APA’s campaign has included a steady stream of messages aimed at Mr. Cole on Twitter under the hashtag of #givestigmatheboot, and more than 100,000 people have seen the messages, including Mr. Cole. In one tweet, he responded: “Intention was to highlight inadequate access to Mental HealthCare & over access to guns- for all.”

APA members who would like to participate in the campaign are urged to join the conversation on Twitter at #GIVESTIGMATHEBOOT.

Study Links Antipsychotics to Cortical Loss in Patients With Schizophrenia

Although it is well established that patients with schizophrenia have deficits in cortical gray matter, a meta-analysis published in Biological Psychiatry suggests that cumulative antipsychotic intake and the type of antipsychotic a patient with schizophrenia takes may influence the degree of gray matter loss over time.

Researchers from the University of Brescia School of Medicine in Italy led an retrospective study to determine if changes in cortical gray matter differ between patients with schizophrenia who take first-generation antipsychotics (FGAs) and those who take second-generation antipsychotics (SGAs). The researchers compiled data from 18 longitudinal magnetic resonance imaging studies—published from January 1, 1983, to March 31, 2014—including 1,155 patients with schizophrenia and 911 healthy controls.

The results showed that patients with schizophrenia showed significantly higher loss of total cortical gray matter volume over time than healthy controls, which was related to cumulative antipsychotic intake during the interval between imaging scans among the longitudinal studies. When comparing changes in cortical gray matter volumes in patients who were treated with FGAs with those who were treated with SGAs, the researchers found that participants who were administered FGAs had greater gray matter loss compared with those who took SGAs.

“On the whole, our results indicate that the putative contributory role of antipsychotic treatment in reducing the volume of cortical [gray matter] in schizophrenia cannot be generalized and appears to be less evident for SGAs, which seem to be associated with less loss of brain tissue,” the study authors wrote.

“Although this is a clinically meaningful result, many issues remain to be clarified: for instance, we still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure (daily dose or cumulative dose) is reached,” Antonio Vita, M.D., the first author on the study, said in a press release. “Clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in the disease.”

For information about the risks and benefits of first- and second-generation antipsychotics, see the Psychiatric News article “First- and Second-Generation Antipsychotics Compared in Federal Agency Monograph.”

(Image: Triff/Shutterstock)

Report Finds 9.4 Million U.S. Adults Had Serious Thoughts of Suicide in 2014

In 2014, an estimated 9.4 million U.S. adults aged 18 or older (3.9% of all adults) had serious thoughts of suicide in the past year, including 2.7 million who made suicide plans and 1.1 million who made a nonfatal suicide attempt, according to a report released today by the Substance Abuse and Mental Services Administration (SAMHSA). The report also shows that these percentages have remained relatively stable since SAMHSA started tracking these issues in 2008.

The findings—which are based on SAMHSA’s 2014 National Survey on Drug Use and Health report, an annual national survey of 67,500 Americans aged 12 and older—point to several groups that may be at a particularly high risk of suicide. For example, 11.9% of adults with a substance use disorder in the past 12 months had serious thoughts of suicide, 3.9% of these adults made suicide plans, and 2.1% of these adults made nonfatal attempts at suicide. Similarly, rates of suicidal thoughts and behaviors were higher among adults who experienced a major depressive episode in the past 12 months. Around 29.5% of these adults reported serious thoughts of suicide, 9.7% made suicide plans, and 3.4% made nonfatal attempts at suicide.

Among adults in 2014 who had serious thoughts of suicide in the past year, nearly half (48.6%) did not receive any mental health services in the past year, and about 1 in 7 perceived a need for mental health care but did not obtain care.

“We can help prevent suicide through effective, science-based services,” Acting SAMHSA Administrator Kana Enomoto said in a press statement. “By reaching out to people contemplating suicide—everyone—family, friends, teachers, faith community leaders, co-workers, health care providers—can make a positive difference.”

SAMHSA is providing free copies of a booklet designed to help people who have attempted suicide take their first steps toward healing and recovery. A Journey Toward Health and Hope: Your Handbook for Recovery after a Suicide Attempt features firsthand experiences of individuals who have survived a suicide attempt and their supporters.

Today is World Suicide Prevention Day. The theme for this year—Preventing Suicide: Reaching Out and Saving Lives—is meant to highlight the importance of support and the role it can play in combating suicide. APA is posting messages on its social media throughout the day on suicide prevention. APA members are urged to join the conversation on Twitter at @APAPsychiatric and #SuicidePrevention and follow American Psychiatric Association on Facebook.

Proposed Insurance Mergers Could Limit Access to MH Care Even More

The proposed mergers of four giant health insurance companies—Anthem-Cigna and Aetna-Humana—will eliminate consumer choice and encourage insurers to raise prices; they are also likely to have an especially dire effect on access to psychiatric care.

That’s what APA President Renée Binder, M.D., and CEO and Medical Director Saul Levin, M.D., M.P.A., told U.S. Assistant Attorney General William J. Baer, in a letter today expressing APA’s grave concerns about the proposed mergers.

“APA agrees with the American Medical Association, the American Hospital Association, and the American Academy of Family Physicians and shares their concern that these proposed consolidations will functionally leave the vast majority of health care administration in the United States to three major insurers, thereby eliminating consumer choice and encouraging insurers to raise prices and reduce quality of care in most markets,” they wrote. “Furthermore, individuals with mental illness, including substance use disorders, are uniquely affected by the impact these mergers will have on access to psychiatric care in insurance plan provider networks. We request that the Department of Justice [DOJ] focus attention in its review of the proposed mergers on each company’s history of restricting access to clinically appropriate psychiatric care, as well as their ability to more severely restrict access to care if such acquisitions are permitted.”

In addition, Binder and Levin noted that seven years after passage of the Mental Health Parity and Addiction Equity Act, insurance companies have continued to use a variety of strategies to restrict access to psychiatric care and that the proposed mergers would likely make it easier for them to do so.

They urged the DOJ, state insurance commissioners, state attorneys general, and Congress to take the following actions:

* Look into the merging parties’ treatment of patients with mental illnesses, including substance use disorders, and critically evaluate the adequacy of the networks by demanding data on claims filed by each psychiatrist listed in the directory.

* Gather claims data on out-of-network versus in-network claims paid for mental health care as compared with other types of health care.

* Compare the denial rates between mental health and other health claims.

* Explore the basis for discriminatory rates paid to psychiatrists versus other physicians for the same CPT codes and associated impacts on access to care.

* Explore the guideline-setting process, instructions, and payment models used by the companies with reviewers.

“After a thorough investigation of existing practices," they concluded, “we are confident the relevant authorities will be convinced that the merged entities would be a threat not only to consumer choice and pricing, but also to consumer mental health and well-being.”

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STARRS Study Finds Link Between TBI and PTSD, Anxiety, Depression After Deployment

Traumatic brain injury (TBI) is associated with a higher risk of posttraumatic stress disorder (PTSD), generalized anxiety, and depression approximately three and nine months after returning from deployment in a combat zone, according to a recent report in AJP in Advance.

Researchers from multiple institutions drew on data from the Pre/Post Deployment Study (PPDS), a prospective, longitudinal component of the Army Study to Assess Risk and Resilience in Service Members (Army STARRS). The PPDS is a multiwave panel survey that collected baseline data from U.S. Army soldiers in three Brigade Combat Teams during the first quarter of 2012, within approximately six weeks of their deployment to Afghanistan. Follow-up data were collected from these same respondents at three times after they returned from deployment: within one month of their return (T1), approximately three months later (T2), and nine months later (T3).

Complete information was available for 4,645 soldiers, approximately 1 in 5 of whom reported exposure to mild or more-than-mild TBI(s) during deployment. The authors found that even after adjusting for risk factors (including predeployment mental health status, severity of deployment stress, and prior TBI history), deployment-acquired TBI was associated with elevated adjusted odds of PTSD and generalized anxiety disorder at T2 and T3 and of major depressive episode at T2. Suicidality risk at T2 appeared similarly elevated, but this association did not reach statistical significance.

“Importantly, PTSD was not the only outcome related to TBI,” said study coauthor Robert Ursano, M.D., director of the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences. “Risk was also increased specifically for generalized anxiety disorder post deployment and for a composite outcome of PTSD, major depressive episode, generalized anxiety disorder, and suicidality. And the more severe the TBI, the greater the risk,” he told Psychiatric News.

“The results suggest that the extent of injury to the brain moderates the likelihood of the development of mental health sequelae and that our focus on post-TBI surveillance needs to be broadened to include not only PTSD but also other anxiety and depressive disorders,” Ursano said.

For related information, see the Psychiatric News article “Army Learning Complex Factors Associated with Soldier Suicide.”

(Image: Robert Ursano, M.D.)

Vietnam War Veterans Still Face PTSD, Depression 40 Years Later

Forty years later, an estimated 271,000 veterans of the Vietnam War have current posttraumatic stress disorder (PTSD) or subthreshold PTSD—one-third of whom also have current major depressive disorder, according to the National Vietnam Veterans Longitudinal Study (NVVLS), published in the September issue of JAMA Psychiatry.

The NVVLS reassessed a sample of 2,348 veterans who were first studied 25 years ago as part of the National Vietnam Veterans Readjustment Study (NVVRS). For the study, researchers used a variety of instruments to evaluate PTSD and depression, including the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the PTSD Checklist for DSM-IV supplemented with PTSD Checklist for DSM-5 items (PCL-5+).

Among male theater veterans, the researchers estimate a current prevalence of war-zone PTSD based on CAPS-5 criteria of 4.5% or 10.8% for current full plus subthreshold PTSD, and 11.8% prevalence based on the PCL-5. For female veterans, the equivalent rates were 6.1%, 8.7%, and 6.6%. PTSD rates were lower for veterans who were posted elsewhere than Vietnam.

The course of the disorder was different between veterans who did and did not serve in Vietnam, said lead author Charles Marmar, M.D., a professor and chairman in the Department of Psychiatry at the New York University School of Medicine. “For era veterans, self-reports of PTSD symptoms during 25 years are low and stable, whereas, for theater veterans, mean levels are higher and increasing.”

The study shows the need for increased access to care and for “anticipating challenges that lie ahead for Iraq and Afghanistan veterans,” Marmar and his colleagues concluded.

“No other study has achieved this quality of longitudinal information, and the sobering findings tell us as much about the Vietnam generation as about the lifelong impact of combat service in general, relevant to all generations,” commented Charles Hoge, M.D., of the Center for Psychiatry and Neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md., in an accompanying editorial.

For more about the psychiatric effects of military service, see the Psychiatric News article “Troops Face Complex, but Not Inevitable, Mental Health Issues.”

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Kenneth Cole Billboard Fuels Harmful Stigma

Last week, fashion designer Kenneth Cole posted a billboard linking gun violence with mental illness.

“Mr. Cole’s statement on gun reform creates a misleading impression that people who suffer from mental illness are violent,” APA President Renée Binder, M.D., wrote in her blog today about the billboard. “This is a disappointing misrepresentation of the facts and only serves to further stigmatize those suffering from mental illness.”

In reality, the vast majority of mentally ill people are not violent, and most violent acts are committed by people who are not mentally ill, pointed out Binder. People with serious mental illness are 11 times more likely to be victims of a violent crime in the past year than the general population.

“The numbers simply do not bear out what Mr. Cole implies on his billboard,” Binder continued. “But he does get one thing right: many Americans with mental health issues don’t get the help they need.”

Barely two out of five adults with mental illness receive needed treatment.

“The right answer here is to get people with mental illness treatment, not marginalize them, especially when stigma is one of the biggest barriers preventing people from receiving care,” wrote Binder.

The Affordable Care Act and the Mental Health Parity and Addiction Equity Act together are helping address many of these barriers, she said. Lowering barriers to care will help get people in treatment earlier and help prevent many of the disabling aspects of mental illness.

Sharing APA’s outrage over the billboard was the New York State Psychiatric Association, which represents APA members in the state of New York.

Under the Twitter hashtag of #givestigmatheboot, APA responded to Cole’s statement with a series of messages to set the record straight. “1 in 4 people with serious mental illness has been the victim of a violent crime in the past year” and “Disappointed with @mr_kennethcole for linking gun violence, mental illness. Follow us to get the facts. #givestigmatheboot” were two of APA’s tweets.

APA members who would like to participate in the social media campaign are urged to join the conversation at #givestigmatheboot.

“We are advocates for reform on this issue, but suggesting that a vulnerable, stigmatized segment of the population is the cause is ignorant, dangerous, and patently false,” concluded Binder.

Nearly 90 Percent of Americans Say They View Mental, Physical Health Equally

About 90% of U.S. adults report that mental health and physical health are equally important, yet more than 30% believe that mental health care is inaccessible and 40% believe it’s something that most people cannot afford, according to a recent national online survey.

The survey, conducted between August 10 and August 12, asked U.S. adults aged 18 and older about their perceptions of mental health, including whether they had ever been diagnosed with or thought they had a mental disorder and the barriers they viewed to treatment. The survey also asked participants about their experiences with and attitudes toward suicide. A total of 2,020 adults completed the survey, and the results were weighted for age within gender, region, race/ethnicity, income, and education where necessary to align them with their actual proportions in the population.

While one-third of adults reported having been diagnosed with a mental health condition by a health care provider, 47% said they may have had a mental health condition at some point, and more than 10% of those surveyed reported missing work days because they were too anxious (14%) or too depressed (16%) to go to work.

Participants’ perceived barriers to seeing a mental health professional included the following: 43% viewed it as “something most people can’t afford,” 31% viewed it as “not accessible for most people,” 30% viewed it as “something people do not know where to find.” However, the majority of the 38% of adults who reported having ever received treatment for a mental health condition said that the treatment was helpful, whether the treatment was in-person psychotherapy (82%), prescription medication (75%), or another form of treatment.

The survey also found that 55% of all Americans have been affected by suicide in some way. The majority of participants believe that better access to psychotherapy or medication (63%), better training for health care providers (62%), more research into how to help people and why people die by suicide (60%), and educating the public about suicide prevention (59%) would help reduce the number of people who die by suicide.

“Progress is being made in how Americans view mental health and the important role it plays in our everyday lives,” said psychiatrist Christine Moutier, M.D., chief medical officer of the American Foundation for Suicide Prevention. “People see the connection between mental health and overall well-being, our ability to function at work and at home, and how we view the world around us.”

For related information on Americans' attitudes toward mental health care, see the Psychiatric Services report "Attitudes About Required Coverage of Mental Health Care in a U.S. National Sample."

(Image: Shutterstock.com/Goodluz)

Meta-Analysis Finds Association Between Obesity and ADHD in Adults, Children

Adults and children with attention-deficit/hyperactivity disorder (ADHD) are significantly more likely than those without the condition to be obese, according to a meta-analysis of studies appearing in AJP in Advance.

Independent studies evaluating whether an association between obesity and ADHD exists have drawn conflicting conclusions. To examine the relationship between obesity and ADHD, an international team of researchers searched through a broad range of databases and unpublished material to identify population-based studies and clinical studies of individuals with ADHD compared with non-ADHD controls.

Of the forty-two studies (which included 728,136 people) selected for inclusion, the researchers found that obesity was significantly associated with an ADHD diagnosis in both adults and children. The estimated prevalence of obesity was increased by about 70% in adults with ADHD compared with adults without ADHD and by about 40% in children with ADHD compared with children without ADHD. The researchers also noted that individuals taking medication for ADHD were not at any higher risk for obesity than those with untreated ADHD.

“Although obesity has been found to be associated with other mental health conditions, such as depression and anxiety, its association with ADHD might be particularly significant for its potential treatment implications,” the study authors wrote. “Assessing the risk for obesity should be part of the assessment and management of ADHD.”

To read more about ADHD, see the Psychiatric News article "Study Suggests ADHD in Adults May Be Distinct Disorder."

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Extended-Release Guanfacine Reduces Hyperactivity in Children With ASD

Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with autism spectrum disorder (ASD), according to a study published in AJP in Advance.

While extended-release guanfacine is approved for children with attention deficit/hyperactivity disorder (ADHD), the medication is not well studied in children with ASD. Researchers from the Research Units on Pediatric Psychopharmacology Autism Network conducted a multisite, randomized clinical trial comparing extended-release guanfacine with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility.

For the study, 53 boys and nine girls, who ranged in age from 5 to 14 years, were randomly assigned to extended-release guanfacine or placebo for eight weeks. The modal daily dose at week 8 was 3 mg/day (range: 1 mg/day to 4 mg/day) for the extended-release guanfacine group and 3 mg/day (range: 2 mg/day to 4 mg/day) for the placebo group.

The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale compared with a 13.2% decrease in the placebo group. The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% for the guanfacine group compared with 9.4% for the placebo group.

The most common adverse events reported by the guanfacine group included drowsiness, fatigue, and decreased appetite.

“Although symptoms of ADHD and ASD often co-occur and may reflect shared underlying genetic risk, the ADHD syndrome in ASD may differ from ADHD in children without ASD,” the researchers stated. “Children with ASD may be internally focused on topics of special interest, find little reward in matters outside of their circumscribed interest, and, consequently, pay little attention to other environmental stimuli. Hyperactivity and impulsiveness in children with ASD appear similar to the hyperactivity and impulsiveness in ADHD and are more amenable to measurement.”

For related information, see the Psychiatric News article "AACAP Updates Guidelines on Autism Spectrum Disorder."

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