FDA Issues Warning on Combined Use of Prescription Opioids, Benzodiazepines

The Food and Drug Administration today announced that it will require class-wide changes to the labels of all prescription opioid medications and benzodiazepines in an effort to inform health care providers and patients of the serious risks associated with the combined use of the medications.

The agency will now require boxed warnings—the FDA’s strongest warning—and patient-focused Medication Guides for prescription opioid analgesics, opioid-containing cough products, and benzodiazepines (nearly 400 products in total), with information about the serious risks associated with using these medications at the same time.

The announcement came after the agency review found the number of patients receiving overlapping benzodiazepine and opioid analgesic prescriptions increased by 41 percent between 2002 and 2014—an increase of more than 2.5 million opioid analgesic patients receiving benzodiazepines. The review also revealed that from 2004 to 2011, the rate of emergency department visits involving nonmedical use of both drug classes increased significantly, with overdose deaths involving both drug classes nearly tripling during this period. Recent studies suggest concomitant use of opioid analgesics and other CNS depressants, including alcohol, is also associated with serious adverse events.

“Health care professionals should limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate,” the agency wrote in a safety announcement. “If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.”

The FDA said it will continue to examine the evidence on the combined use of benzodiazepines or other CNS depressants with medications used to treat opioid addiction and dependence.

Patients and health care professionals are encouraged to report any side effects involving opioids, benzodiazepines, or other medicines to the FDA MedWatch program.

For related information, see the Psychiatric News article “HHS Takes Actions to Expand Treatment, Research In Opioid Crisis.”

Mental Health Improves With Age, Study Suggests

Despite having worse physical and cognitive health than younger adults, older adults report better mental health as they age, according to a study published online in the Journal of Clinical Psychiatry.

The findings were based on telephone interviews and in-home surveys that assessed the cognitive, physical, and mental health of 1,546 adults aged 21 to 99 from San Diego County, California. Participants were excluded from the study if they lived in a nursing home, were known to have received a prior diagnosis of dementia, or had a terminal illness. 

A comparison of the age groups revealed that while physical and cognitive function showed an accelerated decline with age, the age effects on mental health showed a linear increase from the 20s to the 90s. 

“Overall, our findings support the existence of a ‘paradox’ in which aging is associated with better mental health among older adults at the population level despite loss of physical and cognitive function,” wrote Dilip Jeste, M.D., and colleagues at the University of California, San Diego (UCSD). “The magnitude of this apparent change was substantial, with the oldest cohort having mental health scores 1 SD [standard deviation] higher than the youngest cohort’s [mental health scores], in sharp contrast to the 1.5 and 2 SD differences (suggesting declines) in physical and cognitive function, respectively.” 

Jeste is the senior associate dean for healthy aging and senior care and the Estelle and Edgar Levi Chair in Aging at UCSD and a former APA president.

In contrast to positive mental health reported by older adults, the authors found adults in their 20s and 30s reported high levels of perceived stress and symptoms of anxiety and depression.

“This ‘fountain of youth’ was associated with far worse levels of psychological well-being than during any other period of adulthood,” Jeste told Psychiatric News. He noted that “while adolescence has long been an area of social and scientific concern, relatively little attention has been paid to the issues that continue or get exacerbated after adolescence.”

The study concluded, “There is a critical need for lifespan research combining psychosocial and biological sciences to improve our understanding of the processes that underlie increased psychological well-being in later life and to help develop broad-based interventions to promote wellness and mental health in all age groups.”

For related information, see Positive Psychiatry: A Clinical Handbook from American Psychiatric Association Publishing. APA members may purchase the book at a discount.

(Image: Diego Cervo/ShutterStock)

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Your Help Needed to Pass MH Reform Now!

The House of Representatives passed the Helping Families in Mental Health Crisis Act of 2016 (HR 2646) by an overwhelming majority of 422-2 in July. There is now promising momentum to see this legislation passed into law this year, but your help is needed. With Congress on its August recess, APA urges you to contact your senators (junior senator and senior senator) to encourage them to bring the Mental Health Reform Act of 2016 to the floor immediately and vote YES on S 2680. Take action now!

APA Applauds Mental Health Plan Unveiled Today by Hillary Clinton

Democratic presidential candidate Hillary Clinton unveiled a comprehensive mental health plan today that shows high commitment to initiatives for which APA has long advocated.

“The detailed mental health plan outlined by Hillary Clinton is sweeping in nature and, if enacted, would greatly improve the nation's mental health care system,” said APA President Maria A. Oquendo, M.D. “We welcome the attention Clinton is giving to mental health, an issue that affects Americans from all walks of life. Our mental health system needs to be discussed this election season. Americans deserve to know how the candidates plan to address this important issue.”

These are among the plan’s highlights:

• A focus on early intervention efforts, such as the APA’s Foundation’s Typical or Troubled program, which trains educators to quickly identify children in need to behavioral health resources.
• A pledge to enforce the Mental Health Parity and Addiction Equity Act of 2008, which requires insurers to offer coverage for psychiatric illnesses on par with other illnesses.
• The creation of a national initiative headed by the U.S. Surgeon General for suicide prevention. According to statistics cited in Clinton’s agenda, the overall rate of suicide in the United States increased 24% between 1999 and 2014 and is now at its highest level in three decades.
• An effort to increase the integration between medical and behavioral health care systems and expand community-based treatment, which includes reimbursement for collaborative care models and a nationwide strategy to address the shortage of mental health providers. The APA report “Economic Impact of Integrated Medical-Behavioral Healthcare” indicates that system integration could yield an annual savings of $26-48 billion to health care systems.
• A White House Conference on Mental Health within her first year of office to focus greater attention on mental health issues, promote successful interventions, and identify barriers and solutions.

Other aspects of the plan—which cuts across the spectrum of mental health care from discovery to recovery—include boosting support for research into brain development and human behavior and expanding housing and employment opportunities for individuals with mental illness and other disabilities.

“We commend Secretary Clinton for showing that mental health is important to her by calling for a White House Conference on Mental Health within her first year of office,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “This plan—through parity, prevention, early intervention, treatment and recovery—addresses the needs of every American who is affected directly or indirectly by mental illness.”

Clinton plans to hold a town hall meeting by telephone with stakeholders in the mental health area, including APA, later today.

Detailed coverage of Clinton’s plan will appear in a future issue of Psychiatric News.

U.S. Surgeon General Asks Physicians to Pledge Commitment to Stop Opioid Epidemic

In a letter sent to 2.3 million physicians and other health care professionals across the country on Thursday, the U.S. Surgeon General asked them to pledge their support of a national movement to reverse the opioid epidemic in the United States.

“Since 1999, opioid overdose deaths have quadrupled and opioid prescriptions have increased markedly—almost enough for every adult in America to have a bottle of pills. Yet the amount of pain reported by Americans has not changed,” wrote Surgeon General Vivek Murthy, M.D., M.B.A. “Now, nearly 2 million people in America have a prescription opioid use disorder, contributing to increased heroin use and the spread of HIV and hepatitis C.”

The letter—which Murthy noted marks the first sent from his office to health professionals to address a public health crisis—is part of the Surgeon General’s TurnTheTide Campaign, a national effort to raise awareness about those affected by opioid use disorder, successful treatment programs, and the challenges that remain in communities hardest hit by the epidemic.

Murthy asked health care professionals to commit to addressing the growing problem of prescription opioid abuse through several actions:

• Learn how best to treat pain safely and effectively. (The letter directs professionals to a pocket guide based on CDC Opioid Prescribing Guidelines.)
• Screen patients for opioid use disorder and provide or connect them with evidence-based treatment.
• Speak openly about the fact that addiction is a chronic illness that requires treatment.

“I know solving this problem will not be easy. We often struggle to balance reducing our patients’ pain with increasing their risk of opioid addiction. But, as clinicians, we have the unique power to help end this epidemic,” Murthy wrote.

To read more and pledge your support of the Surgeon General’s campaign to end the opioid epidemic and access APA training and other resources on opioid use disorder, click here.

For related information, see the Psychiatric News article “Residents Can Help to Curb the Current Opioid Epidemic” by Rachel Katz, M.D.

Metformin May Curb Weight Gain in Youth Taking Antipsychotics for Autism

Although atypical antipsychotic medications can help to reduce irritability and agitation in youth with autism spectrum disorder (ASD), these medications are known to cause weight gain and may increase risk of diabetes. A small trial published online yesterday in JAMA Psychiatry suggests that metformin, a drug used for treatment of type 2 diabetes, may decrease weight gain in children with ASD.

Evdokia Anagnostou, M.D., a senior clinician scientist at the Bloorview Research Institute in Toronto, and colleagues randomly assigned 61 young people (aged 6 to 17) with ASD to receive metformin or placebo for 16 weeks. (All of the study participants had been taking a stable dose of an atypical antipsychotic for at least one month and had documented weight gain since starting on the medication.) Children aged 6 to 9 received metformin or matching placebo titrated up to 500 mg twice daily; those 10 to 17 received 850 mg twice daily. The primary outcome measure was change from baseline to week 16 in body mass index (BMI) z scores. 

“Metformin was superior to placebo in reducing weight gain associated with atypical antipsychotics,” the researchers reported. “No significant differences were noted in changes of any of the metabolic variables studied.” Overall, metformin was well tolerated, but the authors noted youth taking metformin experienced a higher percentage of treatment days with gastrointestinal adverse events during the 16-week trial.

“Anagnostou et al. have made a significant contribution to the literature and provided clinicians with an effective approach to consider for managing weight gain in youths with ASD treated with atypical antipsychotics,” wrote Christopher McDougle, M.D., director of the Lurie Center for Autism at Massachusetts General Hospital in Lexington, Massachusetts, in an accompanying editorial. “In addition to more studies of this approach, alternative strategies that warrant investigation include the co-administration of topiramate, monotherapy with ziprasidone, and undoubtedly others.”

For more in Psychiatric News about the side effects of antipsychotics in young people, see “Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth.”

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New Model Found Useful for Predicting Alcohol Use in Youth

A study published in AJP Advance shows that combining data from demographic interviews with data from neuropsychological and neuroimaging tests may be useful for predicting adolescents who may be at risk of initiating alcohol use by age 18.

“Previous findings have suggested that a mix of social, psychological, and biological mechanisms contribute to alcohol use during adolescence,” wrote the study authors, a team a behavioral scientists and psychiatric researchers. Neuropsychological and neuroimaging data may provide quantification of underlying behavioral mechanisms of risk for substance use and better help identify at-risk adolescent before they initiate such use.

The study involved 137 substance-naïve adolescents aged 12 to 14. Participants' demographic information was obtained at baseline through interview. Neuropsychological testing at baseline was administered to evaluate the neurocognitive function; structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) were used to assess brain structure. Information on participants' substance use, assessed by the Customary Drinking and Drug Use Record, was updated every six months by telephone interview until the end of the study. 

The results showed that by age 18, 70 adolescents (51%) initiated moderate to heavy alcohol use, and 67 remained nonusers. The combined data model was found to be 74% accurate in predicting such outcomes. In comparison, the demographic model had an accuracy rate of 62%, and the demographic and neuropsychological model, 69%.

In addition, the study identified 34 predictors that contributed to alcohol use by age 18, including being male, higher socioeconomic status, early dating, more externalizing behaviors, worse executive functioning, and thinner cortices, and less brain activation in diffusely distributed regions of the brain. 

"The results provide evidence that multimodal neuroimaging data, as well as neuropsychological testing, can be used to generate predictions of future behaviors with [possibly] significantly better accuracy than demographic information alone," the authors wrote. "Understanding neurocognitive factors that predate substance use initiation is crucial to specifying the consequences of substance use on brain development, as well as identifying at-risk youths and potential targets of preventive efforts." 

(iStock.com/JTobiasonPhoto)

FDA Approves Devices for Assessing Cognitive Function After Brain Injury

Two devices for assessing cognitive function immediately following a suspected brain injury or concussion were approved for marketing by the Food and Drug Administration (FDA) yesterday.

The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and ImPACT Pediatric are the first medical devices permitted for marketing that are intended to assess cognitive function following a possible concussion, according to the FDA. They are intended as part of the medical evaluation that doctors perform to assess signs and symptoms of a head injury.

“These devices provide a useful new tool to aid in the evaluation of patients experiencing possible signs of a concussion, but clinicians should not rely on these tests alone to rule out a concussion or determine whether an injured player should return to a game,” said Carlos Peña, Ph.D., M.S., director of the Division of Neurological and Physical Medicine Devices at the FDA’s Center for Devices and Radiological Health, in a statement announcing the approval.

ImPACT software runs on a desktop or laptop and is intended for use with those aged 12 to 59, while the ImPACT Pediatric runs on an iPad and is designed for children aged 5 to 11. 

ImPACT and ImPACT Pediatric are not intended to diagnose concussions or determine appropriate treatments. Instead, they are meant to test cognitive skills such as word memory, reaction time, and word recognition, all of which could be affected by a head injury. The results are compared with an age-matched control database or to a patient’s pre-injury baseline scores if available.

Only licensed health care professionals should perform the test analysis and interpret the results.

The FDA reviewed ImPACT through its de novo classification process, a regulatory pathway for novel, low- to-moderate-risk medical devices that are first of a kind and for which there are special and general controls to provide a reasonable assurance of safety and effectiveness of the devices. The assessment tools are manufactured by ImPACT Applications in Pittsburgh, Pennsylvania.

For related information, see the Psychiatric News article "Computer-Based Tool Can Offer Rapid Screening After TBI."

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New Scoring System May Improve Reliability of PMDD Diagnosis

Premenstrual dysphoric disorder (PMDD)—which was added to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)—is a debilitating condition characterized by the emergence of mood and emotional symptoms in the luteal phase of the menstrual cycle.

This condition is difficult to diagnose, however, because doing so prospectively requires the evaluation of daily symptom ratings and their fluctuations over a two-month period. As such, many clinicians make decisions through a retrospective analysis of a patient’s symptoms, which is known to be prone to false positives, according to the authors.

A study published in AJP in Advance has proposed a new approach termed the Carolina Premenstrual Assessment Scoring System (C-PASS). Through this computerized procedure, clinicians can enter patient-provided ratings on a spreadsheet that determines a PMDD diagnosis based on a standardized thresholds. 

The study authors compared the C-PASS diagnoses of 200 women who had submitted their symptom ratings each week with those of an expert clinician who also reviewed prospectively and found a 94.5% agreement between the two (11 disagreements).

“The current C-PASS materials may be immediately useful clinically,” the study authors concluded. “However, additional development is needed to digitize data collection and streamline the diagnostic process for clinical application.”

(istock/KatarzynaBialasiewicz)

Probiotics Alone May Be Unlikely to Reduce Risk of Depression, Report Finds

Past reports suggest the consumption of foods containing probiotics, such as yogurt, may lead to health benefits, including lower fasting glucose and blood pressure levels. Do probiotics also lower the risk of depression?

According to a large cross-sectional study published today in the Journal of Neuropsychiatry and Clinical Neurosciences, the answer appears to be no. 

Researchers from the Department of Epidemiology at Janssen Research and Development in Titusville, New Jersey, assessed 18,019 adults who participated in the National Health and Nutrition Examination Survey (NHANES). As part of this survey, participants were asked to estimate the types and amounts of foods and beverages consumed during the 24-hour period prior to the interview. Depression was measured with the Patient Health Questionnaire (PHQ-9). (Participants were classified as having moderate or more severe depressive symptoms if PHQ-9 scores were 10 or greater and a score of 5 or greater was used to classify subjects with mild to more severe depressive symptoms.)

About 14% of the participants reported consuming probiotics, primarily through their diet. When making an unadjusted comparison, the probiotic users did have about half the odds of depression as non-users (odds ratio of 0.58); however, this did not factor in that people in the probiotic group were more likely to be white, older, women, healthier, and to have higher family income.

When the analysis was adjusted, the association between probiotic exposure and depression disappeared, irrespective of how depression was defined. Excluding the small subset of people who took probiotics via supplements also did not affect the results.

“These findings suggest that it is not the probiotic exposure itself, but the attributes of subjects who consume probiotics, which lessen the odds of depression,” the authors wrote. “Although these data can provide insight, information on usual dietary practices collected over time would be expected to provide a stronger indication of associations between dietary factors and health outcomes.”

For related information, see the Psychiatric News article “Food May Be a Tool to Consider When Helping Psychiatric Patients,” by Drew Ramsey, M.D.

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Antipsychotic Use Early in Pregnancy Does Not Appear to Increase Risk of Birth Defects

With the possible exception of risperidone, taking antipsychotics early in pregnancy does not appear to significantly increase the risk of newborns having birth defects, a study published yesterday in JAMA Psychiatry reports. According to the study authors, more research is needed to understand the small increase in risk for malformations associated with risperidone.

To examine the risk for congenital defects associated with first-trimester exposure to different antipsychotics, Krista Huybrechts, M.S., Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues analyzed a nationwide sample of over 1.3 million pregnant women enrolled in Medicaid. Exposure to antipsychotics was defined as filling at least one prescription during the first 90 days of pregnancy, and congenital malformations overall and cardiac malformations were assessed during the first 90 days after delivery.

Among the 1,341,715 pregnancies included in the study cohort, 9,258 women (0.69%) filled a prescription for an atypical antipsychotic during the first trimester, and 733 women (0.05%) filled a prescription for a typical antipsychotic. The most frequently used atypical antipsychotic was quetiapine, followed by aripiprazole, risperidone, olanzapine, and ziprasidone.

The authors found that overall, 32.7 per 1,000 infants not exposed to antipsychotics were diagnosed with congenital malformations compared with 44.5 per 1,000 infants exposed to atypical antipsychotics and 38.2 per 1,000 infants exposed to typical antipsychotics. 

While unadjusted analyses suggested an increased risk of birth defects with atypical antipsychotics (relative risk [RR], 1.36) but not for typical antipsychotics (RR, 1.17), after controlling for potential confounding by mental and physical comorbid conditions and their associated behaviors, these relative risks fell to 1.05 and 0.90 for atypical antipsychotic and typical antipsychotic exposure, respectively. Additional analysis revealed that women taking risperidone were 26% more likely than women not taking antipsychotics to give birth to an infant with a birth defect.

“The small increase in absolute risk and RR for malformations observed with risperidone should be interpreted with caution because no apparent biological mechanism can readily explain this outcome, and the possibility of a chance finding cannot be ruled out,” the authors wrote. “This finding should therefore be interpreted as a potential safety signal that will require follow-up in other studies.

Reflecting on the findings in a related editorial, Katherine Wisner, M.D., M.S., and colleagues wrote, “The sophisticated pharmacoepidemiologic methodology comprehensively tackles the major challenge in observational studies, that is, confounding by underlying disease factors that are (like the APs [antipsychotics]) potentially associated with pregnancy outcomes. The task is to separate the effect of two exposures (APs and psychiatric disease) on the reproductive outcomes. The finding that “associations between AP exposure and birth defects were attenuated after adjustment for confounding ... implies that these variables, rather than AP exposure, account for much of the effect on congenital malformations.”

For related information on weighing the risks and benefits of medications when treating pregnant women, see the Psychiatric News article “Yes or No: Prescribing Antidepressants to Pregnant Patients” by Jennifer L. Payne, M.D.

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Report Finds YouTube Presents ‘Distorted Picture’ of Schizophrenia

Although many people may turn to YouTube for information on a variety of health conditions, few studies have investigated the accuracy or quality of the information on mental illness presented in these videos. A study published this week in Psychiatric Service in Advance has concluded that schizophrenia presentations on the global video-sharing site “offer a distorted picture of the condition.”

For the study, a team of researchers from the United Kingdom performed a search for all YouTube videos purporting to show footage of individuals exhibiting the signs and symptoms of acute schizophrenia. Eligible videos were independently rated by two consultant psychiatrists on two separate occasions for probable psychiatric diagnosis and psychopathological symptoms; the raters were also asked to answer the yes-or-no question “Considering the quality and content of this video, would you consider using it in a medical student teaching session as an illustration of the signs and symptoms of acute psychosis in schizophrenia?” Videos receiving a “yes” response by both independent raters were considered to have good educational utility.

Of the 4,200 videos assessed, 35 videos met the authors’ eligibility and adequacy criteria. Of these 35 videos, only 12 were considered to present accurate depictions of acute schizophrenia. Compared with cases with a diagnosis other than schizophrenia, schizophrenia cases had a significantly higher prevalence of persecutory delusions (83% versus 15%), inappropriate affect (75% versus 8%), and negative symptoms (83% versus 15%). Of all adequate cases, 16 (46%) were deemed by both raters to have good educational utility.

“Our main findings were that eligible videos were largely inaccurate, containing psychopathological features not specific to schizophrenia,” the researchers wrote. “These findings are important for psychiatrists, given that the Internet has a vast amount of medical information that is easily accessible to medical students.”

While the authors noted that the study did not investigate how YouTube videos may affect understanding of schizophrenia by students, they emphasized “Mental health professionals and medical schools should be aware of this source of inaccurate information when advising students and patients about sources of health information.”

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Early Improvement in Work Productivity May Predict Treatment Success in Depression

Patients with depression who report robust improvement in work productivity in the first few weeks of treatment may be most likely to remain in remission several months later, according to a report in AJP in Advance. The findings highlight the potential value of including work productivity assessments as part of routine clinical practice when evaluating the effectiveness of antidepressant treatment.

Researchers from the departments of psychiatry and clinical sciences at the University of Texas Southwestern Medical Center, Dallas, and the National University of Singapore analyzed remission data from the Combining Medications to Enhance Depression Outcomes trial. This multisite, single-blind, randomized, controlled trial of outpatients with chronic and/or recurrent nonpsychotic depression compared the effectiveness of antidepressant monotherapy (escitalopram plus placebo) with combination therapies (buproprion plus escitalopram or venlafaxine plus mirtazapine). As part of the original trial, the researchers measured work productivity at baseline and at each study visit throughout the trial.

Analysis of these self-reports revealed three distinct trajectories of work productivity during the first six weeks of treatment: robust early improvement (24% of participants), minimal change (49% of participants), and high-impairment slight reduction (27% of participants). (Work productivity outcomes were similar for SSRI monotherapy and the buproprion and venlafaxine combinations, controlling for baseline severity; all work productivity outcomes significantly improved after 12 weeks of treatment.)

Compared with other patients, patients who had “robust early improvement” had three to five times higher remission rates at three months and two to five times higher remission rates at seven months, even after the researchers controlled for select baseline variables and remission status at week six.

“We have ... demonstrated that early changes in work productivity are significant predictors of long-term clinical course,” the researchers wrote. “These findings highlight the multidimensional improvement with antidepressant treatment and argue for inclusion of work productivity assessments in routine clinical practice.”

For related information, see the Psychiatric News article "Mental Health in Workplace Integral to Business Success, CEOs Say.”

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First Suicide Attempts More Lethal Than Prior Estimates

First suicide attempts are more deadly than hitherto appreciated, so prevention efforts should focus on people at risk of making that initial attempt, according to a study from the Department of Health Sciences Research at the Mayo Clinic in Rochester, Minnesota, published today online in the American Journal of Psychiatry.

Using data from the Rochester Epidemiology Project, Mayo’s J. Michael Bostwick, M.D., and colleagues found that 1,490 residents of Olmsted County, Minnesota, made a first suicide attempt between 1986 and 2007, with follow-up through the end of 2010. Of those, 81 died—48 on that first attempt and 33 on a later attempt, most within the following year.

Men were more likely to use guns to kill themselves. Both men and women who used firearms were 140 times more likely to die than those using other methods. Overall, 57 percent of the attempts involved medication overdoses.

Encouragingly, however, scheduling a follow-up psychiatry appointment for survivors sharply lowered the chances of a second suicide attempt that was successful (odds ratio=0.212).

The researchers noted that this is the first study to show odds for dying by suicide in a representative community sample of first lifetime suicide attempters who came to medical attention—a group previously ignored in calculations of risk.

“We contend that counting both index and subsequent attempt deaths more accurately reflects prevalence,” concluded Bostwick. “Our findings support suicide attempt as an even more lethal risk factor for completed suicide than previously thought.”

For more in Psychiatric News about suicide prevention, see “Gun Policy and Suicide Prevention."

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Expert Offers Advice to Improve Medication Adherence

“Working collaboratively with patients to treat their conditions and meet their health goals is an approach that can help to reduce the problem of medication nonadherence,” writes Chris Bojrab, M.D., president of Indiana Health Group, in the latest issue of Psychiatric News PsychoPharm.

Not all patients take all their medications all the time, notes Bojrab. Nonadherence may not be a willful act. Many patients may have a hard time understanding when and how they’re supposed to take their medications, so carefully explaining treatment goals and possible side effects is critical. Others may be deterred by cost or hampered by advancing age. Some may discontinue taking drugs because of side effects but not tell their doctor.

“Let the patient know that there are other options available if the recommended treatment doesn’t work, is not well tolerated, or is not affordable,” said Bojrab.

Read other tips that Bojrab offers to improve patient compliance in the PsychoPharm article.

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Hospitalization With Infection May Increase Long-Term Risk Suicide

Patients who have been hospitalized with infections may be at an increased risk of death by suicide, according to a study published Wednesday in JAMA Psychiatry. The findings add to a growing body of evidence supporting a link between infection, inflammation, psychiatric disorders, and suicidal behaviors.  

To investigate the associations between infectious diseases and the long-term risk of death by suicide, a team of researchers from Denmark and the United States analyzed data contained in Danish registers on more than 7 million people 15 years or older over a 32-year follow-up period. The study authors defined a history of infection as one or more infection diagnoses listed in the national hospital register.

Of the 7.22 million individuals observed in the study, 809,384 had a hospitalization with infection, and 32,683 died by suicide. Of those who died by suicide, 7,892 (24.1%) had previously been diagnosed as having an infection during a hospitalization. 

The authors found that the relative risk of suicide was increased among individuals with any hospitalization with infections by 42% compared with individuals without prior infection; the greater the number of hospital contacts for infections and days spent in treatment, the greater the risk of death by suicide. With the exception of pregnancy-related infections, all other infections examined were linked to an increased risk of suicide, which was most pronounced for HIV or AIDS, hepatitis, respiratory tract, and sepsis infections.

“Although psychiatric disorders and previous suicide attempts might constitute stronger predictors of suicide, we found that hospitalization with infection accounted for a population-attributable risk of 10.1%,” Helene Lund-Sorensen, B.M., and colleagues wrote. If the association between infection and the risk of death by suicide is determined to be causal, “identification and early treatment of infections could be explored as a public health measure for prevention of suicide,” they concluded. 

“There is an imminent need to develop better biomarkers indicating patients at risk for suicide and improved treatment options that are personalized for persons vulnerable to suicidal behavior,” wrote Lena C. Brundin, M.D., Ph.D., and Jamie Grit, B.Sc., of the Van Andel Research Institute in Grand Rapids, Michigan, in a related editorial. “It will be important to understand how milder and long-term infections contribute to depression and suicidality.” Such infections, they noted, often go untreated and remain latent in the body for years.

For related information, see the Psychiatric News article “Researchers Consider Infection as One Cause of Depression.”

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Everett Appointed Chief Medical Officer of SAMHSA

APA President-Elect Anita Everett, M.D. (pictured left), today was named the Chief Medical Officer at the Substance Abuse and Mental Health Services Administration (SAMHSA). She is expected to begin her duties at SAMHSA on September 5.

In her new role, Everett will lead the newly created Office of the Chief Medical Officer, which is expected to provide valuable input into strategic initiatives, policy directions, and legislative issues to ensure that medically researched and clinically approved practices are incorporated in the development and implementation of SAMSHA programs and activities. The office will also play a key role in representing SAMHSA’s clinical perspectives, particularly when working with other Department of Health and Human Services (HHS) entities and federal agencies.    

“I’m really excited and really looking forward to starting the new position as Chief Medical Officer at SAMHSA,” Everett told Psychiatric News. “Having a psychiatrist as a member of the leadership team at SAMHSA will enable psychiatrists to join other mental health and public health professionals in guiding the federal component of our nation's behavioral health system.”  

Everett is currently the division director of Johns Hopkins Community and General Psychiatry, Bayview Campus, and an associate professor in the Department of Psychiatry at Johns Hopkins School of Medicine in Baltimore, where her research focuses on health behavior of individuals with long-term mental illness. 

Everett was elected president-elect of APA in February and will assume the office of president at the conclusion of the APA Annual Meeting in San Diego in May 2017. She has held numerous leadership roles within the organization, which include trustee-at-large on the APA Board of Trustees and chair of the APA Task Force on Healthcare Reform 2015. 

“SAMHSA has selected a great physician whose experience and expertise as a psychiatrist will add value to SAMHSA through its newly created medical office,” said APA President Maria A. Oquendo, M.D. “Her experience will also benefit providers of prevention, treatment, and recovery services for those with mental illness. We look forward to working with Dr. Everett in her new role and with SAMHSA and HHS.”

To read more about Anita Everett, M.D., see the Psychiatric News articles “Everett Chosen APA’s Next President-Elect” and “APA Continues Charting Course on Health Care Reform.”

Meta-Analysis Suggests SSRI Treatment Gains Happen Early in Pediatric OCD Patients

Patients with pediatric obsessive-compulsive disorder (OCD) show the greatest response to SSRIs early, with most improvements seen within two weeks after starting the medication, according to a meta-analysis published online August 4 in the Journal of the American Academy of Child and Adolescent Psychiatry.

While current guidelines support the use of cognitive-behavioral therapy and SSRIs as first-line treatments for OCD, the findings suggest clinicians may not need to wait eight to 12 weeks (as is currently recommended) before adjusting pharmacotherapy if a child shows no improvement on the medication. 

Anjali Varigonda, M.D., a PGY-2 in psychiatry at the University of Vermont Medical Center, Burlington, and colleagues identified nine randomized, controlled trials comparing SSRIs (fluoxetine, fluvoxamine, paroxetine, and sertraline) or clomipramine to placebo for the treatment of pediatric OCD. The researchers extracted weekly symptom data from trials in order to characterize the trajectory of pharmacological response to SSRIs.

They found a significant benefit of SSRI compared with placebo as early as two weeks after the initiation of treatment in pediatric OCD. Over 85% of the improvement observed on SSRI compared with placebo in pediatric OCD trials was observed by week 2.

The meta-analysis also found the tricyclic antidepressant clomipramine to be more effective than SSRIs when both agents were compared with placebo in children with OCD; however, the authors cautioned much of clomipramine’s apparent increased efficacy may be due to the fact clomipramine trials were performed earlier on likely less refractory pediatric patients with OCD (When meta-analysis was restricted to examining SSRI agents, there was a significant relationship between measured efficacy of SSRIs and publication year). The researchers also noted that clomipramine has significant side effects, including weight gain, anticholinergic side effects, and arrhythmias, making it a less-desirable first-line drug.

The findings “may possibly suggest that pharmacotherapy trials of 8-12 weeks may not be necessary and that if a child shows no improvement with SRI treatment, trial durations could potentially be shorter,” the authors wrote. “However, before a change in guidelines is considered, there needs to be more OCD pharmacological research that focuses on the prognostic utility of early SSRI response data on individual patient outcomes. Additionally, more effective, evidence-based treatments for SRI-refractory pediatric patients with OCD are needed, as there is limited guidance for further treatments once SRIs and CBT prove unhelpful.”

For related information, see the Psychiatric News article “How Effective Are Antidepressants in Youth?”

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Combining SSRIs With Statins May Boost Antidepressant Effectiveness

A study in the August issue of American Journal of Psychiatry suggests that statins, drugs that help lower cholesterol, may boost the effectiveness of antidepressants.

The findings come from an analysis of Danish health registers, which identified 872,216 people who used a selective serotonin reuptake inhibitor (SSRI) between 1997 and 2012; 13% of these users (113,108) also used a statin at the same time.

People who were taking the SSRI/statin combination were less likely than those who were taking SSRIs alone to visit a psychiatric hospital for any condition (odds ratio=0.75), as well as specifically for a depression diagnosis (odds ratio=0.64).

The vast majority of users were taking citalopram and simvastatin; thus, that drug combination is likely the driving force behind these results, according to the researchers.

The researchers also found that the combination of the two drugs did not increase the likelihood of death or suicidal behaviors (suicide and attempts) compared with SSRIs alone. An exploratory look at individual drug combinations suggested, however, that the joint use of any SSRI with lovastatin might increase mortality risk, but this outcome was very rare.

The researchers concluded that the antidepressant potential of the SSRI-statin combination warrants further testing in larger randomized, controlled trials, concluded the researchers. In particular, they noted that the specific combination of citalopram/simvastatin would be a good candidate for a head-to-head study against a citalopram-placebo combination.

To read about the effects of antidepressant use on cardiac conditions, see the Psychiatric News article "Antidepressants May Help Improve Heart Health."

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Could Class Substitution by Pharmacists Put Patients at Risk?

Should generic medications be substituted at the pharmacy for prescribed brand-name formulations?

Psychiatric News spoke with clinicians about “generic substitution”—the practice of substituting a generic equivalent of a brand-name drug—and the more controversial cost-control practice known as “therapeutic substitution.” The latter, which is the substitution of a different, lower cost molecule for another prescribed medication in the same “therapeutic class,” was the focus of a recent report in JAMA Internal Medicine that highlighted the potential cost-saving implications of therapeutic substitution.

“The take home from the study is that prescribing in United States is inefficient,” study author Michael Johansen, M.D., told Psychiatric News. “Too many branded drugs are used, when generics will work equally effectively at dramatically lower prices. This does not mean we shouldn’t prescribe branded drugs, but this should be restricted to times when it is absolutely necessary.”

Generic substitution is widely legal and commonly practiced. But therapeutic substitution—dispensing a different drug in the same therapeutic class—is well outside the norm. A law approved by the Arkansas state legislature in 2013 appears to be the first to legally sanction therapeutic substitution by a pharmacist.

Clinicians who spoke with Psychiatric News were unanimous that therapeutic substitution was at least unwise, and possibly dangerous.

“We know that even within relatively well-defined classes, not all drugs are the same, especially when it comes to side effects, drug interactions, and patient tolerance,” said Glenn Martin, M.D. (pictured above), immediate past speaker of the Assembly. “Psychiatrists understand and value the important role of pharmacists and are happy to collaborate with them. But class substitution without prior specific approval by the physician is not in the patient’s best interest and should definitely not be allowed to be mandated as a cost saving tactic.”

For more coverage of this issue, see the full story “Generic, Class Substitution of Meds: Does it Harm Patients?” in today’s issue of Psychiatric News PsychoPharm. For more information on APA’s reaction to the Arkansas law on therapeutic substitution, check out “Assembly Responds to Arkansas Law on ‘Therapeutic Substitution’.”

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Frequent Patient Contact May Reduce Risk of Relapse in Schizophrenia Patients

Frequent patient contact appears to account for an impressively low relapse rate in both arms of a study comparing long-acting injectable (LAI) antipsychotic risperidone and second-generation oral antipsychotics, according to a report in Psychiatric Services in Advance. 

In a previous report, Peter Buckley, M.D. (pictured left), dean of the Medical College of Georgia Regents University in Augusta, and colleagues compared relapse in 305 patients with schizophrenia or schizoaffective disorder who were randomly assigned to LAI risperidone or oral second-generation antipsychotics. The results of the PROACTIVE trial (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) revealed no difference in overall rate of relapse between the two groups (42% with injectable medication, 32% with oral medication) and no significant difference between the groups in time to first relapse.

In the follow-up study published in Psychiatric Services, Buckley and colleagues compared second and third relapses between patients who continued in their randomized treatment (147 in the injectable medication group and 151 in the oral medications group) to assess whether experience of relapse had a differential impact on subsequent relapse among those receiving injectable or oral medication.

Thirty-two patients (11%) experienced a second relapse—16 in the injectable medication group and 16 in the oral medications group. Thirteen patients (4%) experienced three relapses—five in the injectable medication group and eight in the oral medication group. There was no statistically significant difference between the two treatments.

In an interview with Psychiatric News, Buckley emphasized the “pragmatic” design of PROACTIVE and its follow-up—patients and clinicians in the study were allowed greater flexibility to address problems in treatment, as would be more likely in day-to-day clinical practice, in contrast to the strict protocols typically imposed in a standard clinical trial. Specifically, patients in the oral medication group were allowed flexibility to change medications, and patients in both arms received biweekly meetings with clinicians and staff to monitor compliance.

“Two things seem to account for [the lack of difference between the two treatments],” Buckley told Psychiatric News. “First, what drives the perceived benefit of injectable medication is that you have a greater assurance patients are taking their medication. But in this study, we washed out that benefit because both groups were under the watchful eye of our team. Second, all the patients were seen every two weeks, which reduced the overall rate of subsequent relapse.” 

He continued, “We set out to do our best to determine if there was a distinction between the two treatments, but what we ended up showing is that when you provide care in a setting where patients are seen frequently, we can really impact relapse.”

For related information, see the Psychiatric News article “LAI Antipsychotics: Game Changer, or Still Awaiting Evidence of Superiority?”

Patients With Binge-Eating Disorder, Bulimia May Be More Likely to Smoke Cigarettes

People with binge-eating disorder and bulimia nervosa may be more likely to smoke than those without the disorder, according to the results of a meta-analysis in the journal Addiction.

While the association between cigarette smoking and mental illness is well known, the association with eating disorders is less clear. To examine the relationship between smoking and eating disorders, an international team of researchers conducted a meta-analysis of 31 studies comparing the odds of smoking in people with bulimia nervosa, binge-eating disorder, and anorexia versus healthy controls. 

The analysis revealed that people with binge eating-disorder and bulimia nervosa, but not those with anorexia nervosa, were significantly more likely to have a lifetime history of smoking than healthy controls. Among the eating disorders examined, the highest prevalence of smokers was observed in those with binge-eating disorder (47.7%), followed by bulimia nervosa at 39.4%. People with bulimia nervosa also had higher proportions of current smokers than healthy controls. 

The findings suggest “clinicians should ask people with ED [eating disorders] about their smoking status and provide appropriate counselling and interventions,” the researchers wrote. “Further, high-quality studies are needed to assess the time course of ED and smoking, the impact of smoking on the onset and development of medical complications in eating disorders and, most importantly, the effectiveness of interventions aimed at promoting smoking cessation in people with ED.” 

For related information, see the Psychiatric News article “FDA Approves First Drug for Binge-Eating Disorder.”

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To Treat Anorexia Nervosa, Experts Say You Must First Identify Core Fears

To effectively treat patients with anorexia nervosa with exposure therapy, practitioners must first disentangle the feared stimuli and feared outcomes of patients with the disorder, Stuart Murray, Ph.D., of the University of California, San Francisco, and colleagues advised in an article in JAMA Psychiatry. 

“The treatment of AN [anorexia nervosa], by virtue of directly targeting the primary phobic content (i.e., weight gain), inherently centralizes exposure-driven processes. Thus, a comprehensive distillation of the core fear is both novel and necessary in optimizing the potency of treatments,” they wrote. For instance, if food consumption is conceptualized as the core feared stimulus, and weight gain as the feared outcome, it is possible that the introduction of previously eliminated/feared foods alongside the necessary weight gain throughout weight restoration may confirm the notion that these foods are indeed ‘dangerous’ as weight increases. … Alternatively, if one conceptualizes weight gain as the feared cue and aversive self-concept–related consequences as the feared outcome, treatment focusing entirely on food and weight gain may not provide adequate exposure training for violation of this fear.”

The diverse core fears associated with weight gain influence how patients with anorexia will respond to treatment. “For instance, the process of weight restoration may likely impart different cognitive outcomes depending on whether a patient’s core fear association relates to food consumption resulting in weight gain ... or weight gain resulting in self-concept–related aversive outcomes. ...”

The authors concluded, “It is only after the precise delineation of core fear associations in AN that targeted efforts to promote the long-term consolidation of their extinction may be effectively undertaken and tested. The application of exposure therapy without clearly delineating which fear-based expectancy one is attempting to violate is, at best, nonspecific or, at worst, contraindicated.”

For more on eating disorders, see the Psychiatric News column “Recognizing When Food Restriction Has Little to Do With Weight,” by B. Timothy Walsh, M.D., and Evelyn Attia, M.D.

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Children Diagnosed With Autism Early May Be More Likely to Receive Behavioral Intervention

A report appearing today in Psychiatric Services in Advance suggests that the older a child is when diagnosed with autism spectrum disorder (ASD), the less likely it is he or she will receive behavioral intervention, which has been shown to benefit children with the disorder. Instead, the report found older-diagnosed children appear to be more commonly prescribed psychotropic medications.

Katharine Zuckerman, M.D., M.P.H., an assistant professor of pediatrics at Oregon Health and Science University, and colleagues assessed 722 children ages six to 11 diagnosed with ASD, from the Centers for Disease Control’s Survey of Pathways to Diagnosis and Services.

The researchers found that children diagnosed with ASD at four years or older were less likely than children diagnosed at younger ages to receive behavioral intervention (25% versus 44%, respectively) and more likely to receive medications (60% versus 31%, respectively).

A delay in ASD diagnosis—defined as the amount of time between parents’ first discussion of concerns with a provider and ASD diagnosis—also appeared to influence health service use. The use of complementary and alternative medications, such as nutritional supplements, was nearly twice as common among children with longer versus shorter diagnostic delays (21% versus 11%, respectively). As diagnostic delay increased, children with functional limitations became significantly less likely than children without functional limitations to receive school-based therapy, the authors reported.

“Although the optimal type and amount of ASD therapy remain unclear, there is growing consensus that early therapy benefits children and families,” the authors wrote. “It is therefore concerning that nearly a quarter of the elementary school–aged children studied were receiving no school-based therapy, and over half were not receiving BI [behavioral intervention]. Instead, children diagnosed at older ages were more likely to receive psychotropic medications, which generally do not treat core ASD features.”

The authors concluded, “These results suggest that efforts to increase early ASD diagnosis may result in greater ASD-related therapy use and improved functional outcomes for children with ASD.”

To read about efforts to improve early ASD diagnosis, see the Psychiatric News article “Molecular Investigation of Autism May Bring Genetic Diagnosis Closer.”

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