Study Suggests Augmenting CBT With D-Cycloserine May Not Benefit Youth With OCD

Cognitive-behavioral therapy (CBT) with exposure and response prevention (E/RP) is known to help patients with pediatric obsessive-compulsive disorder (OCD), but many remain symptomatic after receiving therapy. While some studies have suggested taking the NMDA partial agonist D-cycloserine before E/RP sessions may help to amplify CBT response, a study published yesterday in JAMA Psychiatry found D-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD.

Eric Storch, Ph.D., of the University of South Florida and colleagues recruited 206 youth aged 7 to 17 with a primary diagnosis of OCD (including a score of at least 16 on the Children’s Yale-Brown Obsessive Compulsive Scale [CY-BOCS]) to receive 10 family-based CBT sessions over 8 weeks. After three initial CBT sessions, 142 youth were randomly assigned to take D-cycloserine (25 or 50 mg) or placebo 1 hour before weekly CBT sessions involving E/RP exercises. The CY-BOCS and Clinical Global Impressions–Severity (CGI-S) were administered at randomization, biweekly, midtreatment, and posttreatment.

The researchers found that the D-cycloserine plus CBT group and placebo plus CBT group declined at similar rates per assessment point on the CY-BOCS total score (−2.31 and −2.03, respectively) and CGI-S (−0.29 and −0.23, respectively). They also found no evidence to suggest concomitant antidepressant medication adversely moderated outcomes.

“The meaningful improvement demonstrated by an abbreviated family-based CBT course independent of D-cycloserine … highlights the importance of CBT dissemination,” the authors noted. “[B]ecause D-cycloserine does not universally enhance or expedite symptom reductions for youth with OCD, other safe and tolerable approaches to enhance fear extinction in E/RP should be explored.”

In a related editorial, Stefan Hofmann, Ph.D., of Boston University reflected on what the findings might mean for future studies considering D-cycloserine as an augmentation strategy.

For related information, see the Psychiatric News article “Antidepressants May Inhibit D-Cycloserine From Improving Symptoms in People With OCD.”

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Study Suggests Religious Service Attendance May Reduce Risk of Suicide in Some Groups

U.S. women who regularly attend religious services may be at significantly lower risk of suicide than women who have never attended religious services, according to a study published today in JAMA Psychiatry.

“[T]he findings … underscore the importance of obtaining a spiritual history as part of the overall psychiatric evaluation, which may identify patients who at one time were active in a faith community but have stopped for various reasons,” Harold G. Koenig, M.D., of Duke University Medical Center, wrote in a related editorial. “Exploring what those reasons were, particularly among the socially isolated, and perhaps supporting a return to such activity, if the patient desires, may help produce social connections that lower suicide risk.”

While previous studies have suggested an inverse association between religious participation and suicide, these studies have largely been limited to cross-sectional or ecologic data. To prospectively explore the effect of religious service attendance on suicide, Tyler J. VanderWeele, Ph.D., of Harvard T.H. Chan School of Public Health, and colleagues analyzed data on 89,708 women aged 30 to 55 who had self-reported information on religious service participation in 1996, as a part of the Nurse’s Health Study. Follow-up for suicide began with the measure of religious service attendance in 1996 and continued until suicide, loss to follow-up, or the end of follow-up in June 2010.

A total of 36 suicides were identified in the population. Statistical analysis revealed that compared with women who never attended religious services, women who attended religious services once per week or more in 1996 had an approximately five-fold lower rate of suicide during the evaluated period.

While the authors acknowledged more research is needed to determine whether their findings are “generalizable to the general U.S. population, to men, to other races, to other countries, or to areas with limited religious freedom,” they concluded that the findings suggest “[r]eligion and spirituality may be an underappreciated resource that psychiatrists and clinicians could explore with their patients, as appropriate.”

“Our results do not imply that health care providers should prescribe attendance at religious services,” the authors wrote. “However, for patients who are already religious, service attendance might be encouraged as a form of meaningful social participation.”

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Adding CBT to Usual Care in Early Intervention for Psychosis Found to Be Cost-Effective

Cognitive-behavior therapy as a preventive adjunct to usual care for patients at ultra-high risk (UHR) for psychosis appears to be more effective at preventing conversion to psychosis and more cost-effective compared with usual care alone in a program for UHR patients. The results appeared online in Schizophrenia Bulletin.

Researchers at the University of Amsterdam analyzed data from the Dutch Early Detection, Intervention, and Evaluation Trial, comparing cost-effectiveness of routine care (RC) only versus routine care with adjunctive CBT (CBTuhr). The primary outcome was treatment response, defined as the proportion of averted transitions to psychosis, and the secondary outcome was gain in quality-adjusted life years (QALYs), a measure of cost-effectiveness.

A total of 101 patients received RC only and 95 received CBTuhr. The researchers found that 24.8% of the RC patients transitioned to psychosis during the four-year follow-up period compared with 12.6% of the CBTuhr patients—a statistically significant difference.

Overall,the combined therapy cost less ($19,121) than routine care alone ($24,898).”The difference between CBTuhr and RC in intervention services received is partly explained by the lower psychosis conversion rate in the CBTuhr group and partly by a generally higher service use in RC,” the researchers state.

In addition, the cumulative gain in QALYs was higher for the CBTuhr group, though this difference was not statistically significant. (QALY in the study was measured using a version of the “EuroQoL” group, which consists of five health state dimensions—mobility, self-care, usual activities, pain/discomfort, and anxiety/depression—on which the respondent rates his/her own health. Each dimension has three levels: no problems, some problems, and extreme problems.)

"This study showed that CBTuhr had an 83% likelihood of resulting in a reduction of the transition to psychosis at a lower cost," the researchers stated. "There was a 75% likelihood that the intervention resulted in more QALY gains at lower costs."

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Pediatricians Urged to Routinely Screen Adolescents for Risk Factors for Suicide

The American Academy of Pediatrics (AAP) today published updated guidelines to assist pediatricians and other child and adolescent health care professionals in identifying and helping adolescents at risk of suicide. The report, which replaces recommendations made in 2007, acknowledges the role bullying and the internet may play in teen suicide risk and highlights the value of antidepressant medications to treat those at risk.

According to most recent data, suicide is the second leading cause of death for adolescents aged 15 to 19. The guidelines recommend pediatricians routinely ask adolescent patients if they have thoughts of harming themselves, and screen for bullying, pathological internet use, and other risk factors including a family history of suicide, a history of physical or sexual abuse, and mood disorders.

If an adolescent is considered to be at moderate or high risk of suicide, the guidelines recommend that arrangements for immediate mental health professional evaluation should be made during the office visit. For teens considered to be at low risk of suicide, the guidelines recommend close follow-up and/or a referral for a timely mental health evaluation.

While the report documents evidence to suggest antidepressants may increase risk of suicide in some adolescents, it also notes “for appropriate youth, the risk of not prescribing antidepressant medication is significantly higher than the risk of prescribing.” It is recommended that pediatricians work closely with families to closely monitor adolescents’ mental health and behavioral status, particularly when initiating or changing antidepressant treatment.

“Pediatricians can enhance continuity of care and adherence to treatment recommendations by maintaining contact with suicidal adolescents even after referrals are made. Collaborative care is encouraged, because it has been shown to result in greater reduction of depressive symptoms in a primary care setting,” the report noted.

For related information, see the Psychiatric News Alert “CDC Report on Suicide Underscores Urgent Need to Identify At-Risk Individuals.”

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Concussions From Youth Sports, Recreation May Be Underreported in Health Care Settings

A study published this week in the journal Pediatrics estimates that between 1.1 and 1.9 million sports- and recreation-related concussions occur annually in U.S. children ages 18 and under. The report concluded that many of these cases are not reported in health care settings.

Previous estimates of sports- and recreation-related concussions have tended to cover organized school athletics but not out-of-school sports or general recreational activities, especially by younger children, Mersine Bryan, M.D., a fellow and acting instructor of pediatrics at the University of Washington, Seattle, and colleagues wrote.

To generate a national estimate of sports- and recreation-related concussions for 2013—the year for which most recent data were available—Bryan and colleagues analyzed data contained in three large national databases that included patients seen in health care settings, as well as concussions reported to high school athletic trainers and documented in recently published literature.

Of the 1.1 to 1.9 million youth believed to be affected by sports- and recreation-related concussions annually, the authors estimated more than half were not seen in health care settings.

“The large number of unreported concussions identified in our study, between 511,590 and 1,240,972, indicates a need for a cultural shift in the recognition of SRRCs [sports- and recreation-related concussions],” said Bryan, calling for a more accurate surveillance system. “Surveillance for SRRCs must focus on recognizing and treating concussions across all age groups and include recreational activities.”

For related information, see the Psychiatric News articles “Baseline Somatization May Predict Sports-Related Concussion Recovery” and “Blood Test May Detect Concussions Days Later.”

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SAMHSA Estimates 1 in 13 Young Adults Experienced Thoughts of Suicide in Past Year

An estimated 2.6 million adults aged 18 to 25 in the United States—roughly 1 in 13 young adults—reported experiencing serious thoughts of suicide in the past year, according to a report by the Substance Abuse and Mental Health Services Administration (SAMHSA).

“Behind the statistics on completed suicides are the troubling large numbers of Americans who think seriously about committing suicide every year and do not receive mental health treatment,” Rachel Lipari, Ph.D., of SAMHSA and colleagues wrote. “Highlighting the prevalence of suicidal thoughts across states may help federal, state, and local policymakers continue to plan for and allocate resources to reduce the negative perceptions associated with mental and emotional issues, seek suicide prevention support, and increase access to mental health treatment.”

The findings of the report were generated from combined results from the 2013 and 2014 National Surveys on Drug Use and Health, which included questions about suicidal thoughts and behaviors over the past year. The estimates do not reflect information from adults whose suicide attempts in the past year were fatal.

The rates of young adults with serious thoughts of suicide over the past year ranged from 6.2% in Texas to 10.3% in New Hampshire. Other states with the highest rates of past-year suicidal thoughts among young adults included Utah, Montana, Michigan, and Ohio; lowest rates were reported in the District of Columbia, Kansas, Mississippi, and Arkansas.

Overall, the rate of serious suicidal thoughts among young adults remained relatively the same between the 2012-2013 period and 2013-2014 period both nationally and within each of the states—with the exception of New Hampshire, where it increased from 8.4% in 2012-2013 to 10.3% in 2013-2014.

For related information, see the Psychiatric News article “Rural Radio Program Becomes Mental Health Outreach to Youth.”

How Much Should Clinicians Pay Attention to the Cost-Effectiveness of Prescriptions?

To what extent should clinicians consider “cost-effectiveness” in the choice of treatment?

That’s a question Psychiatric News posed to several experts following a report in Psychiatric Services in Advance that concluded the long-acting injectable paliperidone, a second generation antipsychotic, is not as cost-effective as haliperidone, despite having a slight advantage in terms of clinical effectiveness.

In the study, Robert Rosenheck, M.D., a professor of psychiatry and public health at Yale Medical School, and colleagues randomized a total of 311 adults with schizophrenia or schizoaffective disorder to monthly intramuscular injections of haliperidone (25 mg to 200 mg) or paliperidone (39 mg to 234 mg) for up to 24 months.

Results showed that paliperidone was associated with a small but statistically significant health advantage over haliperidone—as measured by “quality-adjusted life years.” The cost of paliperidone ran on average $2,100 more per quarter for inpatient and outpatient services and medication compared with haliperidone.

“The results of this study should encourage consideration of older, less expensive drugs, such as HD [haliperidone deconate],” Rosenheck and colleagues wrote. “[A] rational policy for treatment of chronic schizophrenia might limit use of the more expensive LAIs to patients who do not benefit from or cannot tolerate HD.”

In an interview with Psychiatric News, Rosenheck said the results should be useful to payers and policymakers. Clinicians also have a responsibility to pay attention to cost-effectiveness. “If psychiatrists don’t play a role in developing a scientific basis for cost-effectiveness, then the only people who are setting the agenda are those whose main interest is profit,” he said.

Jim Sabin, M.D., director of the ethics program at Harvard Pilgrim Health Care, said decisions about allocation of resources for medications that are marginally more effective but significantly more costly can be made ethically and rationally within a system of care (as opposed to ad hoc decision-making by individual prescribers) that accommodates the imperatives of population health and patient preferences.

“A well-functioning system serves both perspectives,” he told Psychiatric News.

For more coverage of the Rosenheck study—including an explanation of cost-effectiveness methodology—see the Psychiatric News PsychoPharm article “How Much Should Psychiatrists Weigh Costs When Prescribing?”

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How Will MACRA Impact Your Practice?

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) permanently repealed the old Medicare SGR formula and set in motion entirely new programs for quality reporting and new payment models. What will this mean for your practice? On Wednesday, June 29, from noon to 1 p.m., APA will host a live, free webinar to educate you about several key features of MACRA. Click HERE to register for this event.

Review Describes How Genetic Information Can Guide Antidepressant Prescribing

Although antidepressants are one of the most commonly prescribed medications in the United States, it is well known that the safety and effectiveness of antidepressants can vary greatly from one patient to the next. In a review published in Mayo Clinic Proceedings, Malik Nassan, M.B.B.S., and colleagues from the Mayo Clinic describe how using genetic tests that screen for pharmacokinetic metabolizing genes can assist with individualizing antidepressant therapy for patients.

The review describes evidence to support the role of two metabolizing genes—cytochrome P450 2D6 (CYP2D6), known to metabolize fluoxetine, paroxetine, and venlafaxine; and cytochrome P450 2C19 (CYP2C19), known to metabolize citalopram and escitalopram—in the response of patients to antidepressants.

“The evidence-based rationale for CYP2D6 or CYP2C19 genetic testing can be delineated by serum levels, lower tolerability, serious adverse events (blood pressure changes, QT prolongation, seizures, and death), and pharmacogenetics-based primary outcome measures (e.g., antidepressant response),” the authors wrote.

The authors described ways that the results of CYP2D6 or CYP2C19 genetic tests might be used to aid clinicians in the selection of antidepressants: “For example, when prescribing fluoxetine, paroxetine, or venlafaxine to a patient who is a known CYP2D6 poor or poor-to-intermediate metabolizer or prescribing citalopram or escitalopram to a patient who is a known CYP2C19 poor or poor-to-intermediate metabolizer, an alert will appear on the computerized physician order entry system. In the absence of clear FDA guidelines for dose adjustment, an alternative medication that is metabolized by another enzyme should be considered.”

“With the continuous decrease in the cost of genetic testing, the willingness of insurance companies to cover such tests, and the increase in published data providing more robust evidence of clinical importance, CYP2D6/CYP2C19 genotyping might become, in the near future, a routine test before prescribing relevant antidepressants to all patients,” the authors concluded.

“Genetic and other laboratory … tests will increasingly be used in psychiatry over the coming years, and practitioners today need to understand the principles outlined here to be able to utilize these tools in an informed way in the treatment of patients,” Sheldon Preskorn, M.D., of the University of Kansas School of Medicine, wrote in a related editorial. “Nissan et al. have provided a review of the rationale for this inevitability and have presented an algorithm to aid in the selection of antidepressants for patients in whom the genetic information needed is already known.”

The Mayo Clinic has a financial interest in Assurex Health Inc. and the technology referenced in this article. Other support came in part from NIMH, NIAAA, and NIH.

(Image: The Biochemist Artist/Shutterstock)

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How Will MACRA Impact Your Practice?

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) permanently repealed the old Medicare SGR formula and set in motion entirely new programs for quality reporting and new payment models. What will this mean for your practice? On Wednesday, June 29, from noon to 1 p.m., APA will host a live, free webinar to educate you about several key features of MACRA. Click HERE to register for this event.

Integrated Self-Management Interventions Appear Effective

Integrated self-management strategies are designed to help adults with serious mental illness understand, monitor, and manage both their psychiatric disorder and chronic general medical conditions. While previous studies have demonstrated the effectiveness of psychiatric self-management interventions in improving mental health outcomes for adults with serious mental illness, less is known of the effectiveness of integrated self-management interventions.

A systematic review of 15 studies that assessed nine integrated self-management interventions, recently published in Psychiatric Services in Advance, suggests that these approaches are feasible and have a high potential for clinical effectiveness.

The authors noted that “[s]elf-management interventions usually focus on a combination of three tasks: medical management (for example, teaching people how to follow through on treatment), role management (for example, encouraging healthy behaviors), and emotional management (for example, learning how to monitor symptoms and identify early warning signs of relapse).” 

The review revealed that most of the studies established support for the feasibility, acceptability, and preliminary effectiveness of the intervention in regard to enhancing participants’ knowledge of self-management skills, promoting behavioral and attitudinal changes toward managing illnesses, reducing psychiatric symptoms, improving biological indicators of general medical illnesses (such as high blood pressure and weight), and reducing use of acute health services.

The authors cautioned that the impact of the interventions examined “may be limited because of the costly efforts of professional staff and the intensity and duration of these interventions.” They offered several intervention characteristics that may increase the potential for implementation, including greater use of remote technology-based interventions and hiring and training peers to deliver services.

“Our review expands on earlier reviews that focused on general medical self-management only and psychiatric self-management only by focusing on integrated interventions and identifying potential mechanisms to facilitate implementation,” the authors wrote. “Additional efforts are needed to further explore the potential of using emerging technologies to facilitate implementation and delivery of integrated psychiatric and general medical illness self-management programs across the usual clinical settings that serve this population.”

For related information, see the Psychiatric Services article “Organized Self-Management Support Services for Chronic Depressive Symptoms: A Randomized Controlled Trial.”

(Image: Alexander Raths/Shutterstock)

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How Will MACRA Impact Your Practice?

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) permanently repealed the old Medicare SGR formula and set in motion entirely new programs for quality reporting and new payment models. What will this mean for your practice? On Wednesday, June 29, from noon to 1 p.m., APA will host a live, free webinar to educate you about several key features of MACRA. Click HERE to register for this event.

Study Concludes Most Cases of Lithium Intoxication Are Rare, Can Be Safely Managed

A study published this week in the Journal of Psychopharmacology suggests that lithium intoxication in patients with bipolar disorder is relatively rare and can be safely managed in most cases.

Lithium is recommended as a first-line maintenance treatment for bipolar disorder and treatment-refractory depression. While long-term lithium use is associated with an increased risk of loss of renal function and chronic kidney disease, little is known about the incidence, clinical course, and associated factors of acute lithium toxicity.

To determine the frequency of lithium intoxication and the risk for lithium-associated renal dysfunction, a team of Swedish researchers analyzed medical data of 1,340 adult patients who had been exposed to lithium between 1997 and 2013. The authors first calculated the episodes per patient treated over the entire 17-year observation period. Then, they estimated the incidence of lithium intoxication per treatment year based on lithium prescribing data from the Swedish National Board of Health and Welfare.

Of 1,340 patients, 96 (7.16%) had experienced at least one episode of lithium levels equal to or greater than 1.5 mmol/L (lithium intoxication). Further analysis of the medical records of 77 patients with lithium intoxication revealed that while acute kidney injury occurred, renal function after the episode was similar to renal function at baseline. No fatalities occurred in connection with lithium intoxication.

“Ultimately, as lithium intoxication is rare and can be safely managed in most cases, physicians should not withhold lithium for fear of intoxication in patients who benefit from it,” the authors wrote. “In order to manage lithium treatment safely, it is important to educate patients about the risks of lithium toxicity and enable them to understand under which circumstances lithium levels can rise.”

For related news, see the Psychiatric News article “Experts Make Case for Lithium in Youth With Bipolar Disorder.” More information on this topic can also be found in the Bipolar and Related Disorders chapter in The American Psychiatric Publishing Textbook of Psychiatry, Sixth Edition.

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APA Advocacy Ends Denial of Medicare Claims for Several Common Psychiatric Diagnoses

Claims for some 40 diagnostic codes submitted by mental health practitioners participating in the Medicare Part B program in 13 states will no longer be denied, after the Medicare carrier in those states—responding to APA advocacy on behalf of clinicians—updated its Local Coverage Determinations (LCD) to include the codes.

Moreover, claims submitted by practitioners since December 31, 2015, that had been denied will be retroactively approved and paid. The affected states are Arkansas, Colorado, Delaware, the District of Columbia, Louisiana, Maryland, Mississippi, New Jersey, New Mexico, Oklahoma, Pennsylvania, Texas, and three areas in Virginia: Arlington and Fairfax counties and the city of Alexandria.

In response to concerns expressed by APA leadership, Novitas, the Medicare carrier for those states, agreed to update its LCD to include ICD-10 codes that correspond to DSM-5 diagnoses for more than 40 conditions, including some commonly used by psychiatrists—alcohol dependence, major depression, bipolar disorder, anxiety disorder, schizophrenia, and posttraumatic stress disorder (PTSD).

The problems experienced by psychiatrists and others submitting codes for the disorders in the 13 states have to do with the level of specificity required in ICD-10. Users of ICD-10-CM are generally required to select diagnostic codes at the maximum level of specificity in order to get their claims paid; if a subtype or specifier is reflected in the diagnostic code, the user is obligated to indicate it. 

Because the mental disorders section of ICD-10-CM was originally developed in the mid-1990s to correspond to the structure of DSM-IV rather than DSM-5, coded subtypes that appear in DSM-IV but were dropped for DSM-5 have resulted in the diagnostic codes of a number of DSM-5 diagnoses not being accepted by some payers for reimbursement, despite the fact that they are valid ICD-10-CM diagnostic codes.

“This is an example of how APA, working with providers in the field, is able to protect the interests of our members,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “We will continue to work with Medicare carriers in all states to ensure timely payment of claims. And we encourage members to contact APA staff with problems or questions they may have about payment of Medicare claims.”

A list of the diagnostic codes for which services were previously being denied and will now be covered can be found here.

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Study Suggests Long-Acting Opioids Increase Risk of Non-Overdose Death

Patients initiating long-acting opioids for chronic noncancer pain may be at a greater risk of cardiovascular and non-overdose death compared with those initiating anticonvulsants or low-dose cyclic antidepressants, according to a report published Tuesday in JAMA. The findings, the authors wrote, add to the growing body of evidence to support non-opioid therapy for the treatment of chronic pain.

Although long-acting opioids increase the risk of unintentional overdose, few studies have examined their overall safety relative to other medications commonly prescribed to treat non-cancer pain.  

Researchers from Vanderbilt University conducted a retrospective cohort study of Tennessee Medicaid enrollees initiating drug therapy for chronic pain from 1999 to 2012. The study drugs were the long-acting opioids (sustained-release [SR] morphine, controlled-release [CR] oxycodone, transdermal fentanyl, and methadone); the control drugs were either anticonvulsants indicated for chronic pain (such as gabapentin and pregabalin) or low-dose cyclic antidepressants (such as amitriptyline and desipramine).

For their analysis, the researchers compared 22,912 long-acting opioid episodes with an equal number of control medication episodes. They found that patients prescribed therapy for a long-acting opioid had a risk of all-cause mortality that was 1.64 times greater than that for matched patients starting an analgesic anticonvulsant or a low-dose cyclic antidepressant, corresponding to 69 excess deaths per 10,000 person-years of therapy. 

“[O]f the estimated 69 excess deaths per 10,000 person-years of follow-up among long-acting opioid patients, 47 had an underlying cause of death other than unintentional overdose, and 29 had a cardiovascular cause of death,” the authors wrote, adding that the increased risk of cardiovascular death may be related to the adverse respiratory effects of opioids. However, once patients in the long-acting opioid group had more than 180 days of therapy, their risk of death did not differ significantly from that of the control group.

“The study finding that prescription of long-acting opioids was associated with increased cardiovascular and other non-overdose mortality adds to the already considerable known harms of the opioids and thus should be considered when assessing the benefits and harms of medications for chronic pain,” the authors concluded.

For related information, see the Psychiatric News article “AMA Survey Indicates M.D. Support for Measures to Address Opioid Epidemic.” For guidance on prescribing opioids, see information posted on the website of “Choosing Wisely,” a campaign in which APA is a member. Click here and search on “opioid.”

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AMA House of Delegates Calls on Congress to Lift Ban on Firearms Research

Congress should lift a ban that effectively prohibits research at the Centers for Disease Control and Prevention (CDC) on gun violence as a public health hazard, declared members of the American Medical Association House of Delegates today in an emergency resolution approved in the wake of the mass shooting early Sunday morning at an Orlando, Fla., nightclub.

The resolution, which was co-sponsored by the AMA Section Council on Psychiatry, calls on the AMA to “immediately make a public statement that gun violence represents a public health crisis which requires a comprehensive public health response and solution.”

Importantly, the resolution encourages the AMA to lobby Congress to lift a ban approved by Congress in 1996 that prohibits the CDC from funding research that would “advocate or promote gun control”; that ban was an amendment to the Labor-Health and Human Services-Education appropriations bill passed that year, and the language has remained in each subsequent annual funding bill.

The resolution gathered support among AMA delegates soon after the firearms massacre in Orlando, the worst mass shooting in U.S. history. The shooting, which left 49 people dead and many others injured, took place early in the morning of the day that AMA delegates were gathering for reference committee hearings, where reports and resolutions are debated before going before to the full House of Delegates.

By this morning’s vote, more than 50 state and medical specialty societies had signed on as co-sponsors to the resolution, including all of the member groups of the Section Council on Psychiatry.

APA CEO and Medical Director Saul Levin, M.D., M.P.A., said it was long past time to overturn the congressional ban on gun violence research at CDC.

“The massacre in Orlando is just the latest and most horrific instance in an epidemic of gun violence that calls for a comprehensive public health solution,” Levin said. “Last year, APA was one of seven physician organizations that called for policies to reduce firearm-related injuries and deaths. As physicians, we know that research is necessary to point us in the direction of common-sense solutions to this epidemic.”

More coverage of the AMA’s resolution on gun violence will appear in an upcoming edition of Psychiatric News.

For related information, see the Psychiatric News article “Experts Discuss Efforts Required to Reduce Gun Violence.”

Florida Psychiatrists Respond to Mass Shooting in Orlando

The slaughter of 49 patrons of a gay night club in Orlando, Fla., early Sunday morning was exceptional in its horror only in that more people died than in any other mass shooting in U.S. history.

“We are deeply saddened by the senseless violence in Orlando this weekend,” said APA President Maria A. Oquendo, M.D., in a statement. “The notion that the potential motive for targeting the patrons of this nightclub was because of their sexual orientation is disturbing. ... We offer our deepest sympathy and condolences to the victims and their families. APA is a healing organization and our members will be there to help the community of Orlando heal.”

The motives of the gunman, Omar Mateen, who was eventually killed by police, were not entirely clear. News reports said he previously had made antigay remarks, and he declared his allegiance to the Islamic State (ISIS) during the attack.

In Orlando, Florida Psychiatric Society (FPS) members were beginning to work with the Zebra Coalition, a network of organizations that provide services to lesbian, gay, bisexual, and transgender youth, said FPS Executive Director Margo Adams.

Other members are working with the mayor’s office to assist citizens who are calling there for help. Psychiatrists from elsewhere in the state are likely to become involved as well, since club patrons were not only from the Orlando area.

“Mass shootings are a far-too-common form of terrorism in our nation,” said Robert Ursano, M.D., chair of APA’s Committee on Psychiatric Dimensions of Disaster. “Terrorists attack the fault lines in our society, at the boundaries of sexual preference or race or ethnicity, so it’s important for our nation and our communities to stand together.”

More coverage of the events in Orlando will appear in the July 1 issue of Psychiatric News.

(AP Photo/Chris O'Meara)

Can Maintenance TMS Prevent Relapse in Patients With Treatment-Resistant Depression?

While the majority of clinical research efforts to date have focused on understanding the role of transcranial magnetic stimulation (TMS) as an acute treatment for depression, a growing body of evidence suggests that TMS used as a maintenance therapy is an effective strategy for preventing relapse in patients with treatment-resistant depression, according to Joan A. Camprodon, M.D., Ph.D., M.P.H. (pictured left), an assistant professor of psychiatry at Harvard Medical School, who wrote a column on this topic in a recent issue of Psychiatric News PsychoPharm.

A longitudinal study of 257 adults with treatment-resistant depression found that 70.5% of patients who remit after a full course of TMS remain in remission a year later, and 62.5% of patients who respond retain the therapeutic benefit over the same period. However, 36.2% of the patients followed in this study required more TMS treatments during the one-year follow-up period, ranging from a couple booster sessions to an additional full course (the mean number of sessions was 16.2).

“Interestingly, additional TMS was more likely in the subgroups that obtained initial benefit (42.1% of remitters and 61.4% responders versus 32.2% of partial responders and 19.5% of nonresponders),” Camprodon wrote. “These data tell us two things: the effects of TMS are durable, and additional TMS after the acute course of treatment may have a role in keeping patients well.”

Determining the most effective maintenance protocol for TMS as well as the patients who are the most appropriate to receive it will require appropriately powered clinical trials specifically designed to answer questions related to maintenance, Camprodon noted. “In the meantime, clinicians (and health insurance companies) need to make decisions about the most effective (and cost-effective) treatment choices for patients who are presenting for treatment today.”

For related news, see the Psychiatric News article “Neuromodulation May Benefit Patients With Varying Psychiatric Illnesses,” by Andrew Leuchter, M.D.

(Photo Courtesy of Joan A. Camprodon)

Study Suggests Untreated Depression During Pregnancy May Increase Risks to Infants

Untreated depression in pregnant women may increase the risks of preterm birth and low birth weight, according to a study published yesterday in JAMA Psychiatry.

“These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment,” wrote Alexander Jarde, Ph.D., a postdoctoral fellow in the Department of Obstetrics and Gynecology at McMaster University in Hamilton, Ontario, and colleagues.

The researchers systematically reviewed 23 prospective observational studies, including 25,663 women. Pregnant women with untreated depression had a significantly increased risk of preterm birth (before 37 weeks; odds ratio[OR]=1.56) and low birth weight (less than 2,500 grams; OR=1.96) compared with women without depression.

Additional analysis revealed that the odds of preterm birth in studies with authors reporting conflicts of interest (direct or indirect funding by or links to pharmaceutical companies) were significantly higher than in studies not reporting such conflicts—a difference the authors noted was “not explained by either differences in depression severity or study quality and remains to be fully understood.”

The authors concluded, “Our findings have important clinical implications for pregnant women and health care professionals because they suggest the need for more surveillance for preterm birth and small infant size, key perinatal outcomes in women with untreated depression.”

For related information, see the Psychiatric News article “Yes or No: Prescribing Antidepressants to Pregnant Patients,” by Jennifer L. Payne, M.D.

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Citalopram May Offer Limited Benefit for Patients Experiencing Complicated Grief

Use of citalopram alone or in combination with psychotherapy for complicated grief (CG) may do little to help patients experiencing the persistent maladaptive thoughts, dysfunctional behaviors, and poorly regulated emotionality that characterize this chronic condition, according to findings published today in JAMA Psychiatry. However, a combination of citalopram and complicated grief therapy (CGT) may lead to improvements in patients with complicated grief and co-occurring depression. 

Although it is common for patients with CG to experience co-occurring depressive symptoms, the primary symptoms of CG and response to treatment differ from that of major depression. For instance, past studies have found patients with CG respond better to psychotherapy that targets adaptation to loss than interpersonal psychotherapy, which has well-documented efficacy for depression. However, it is unknown whether antidepressant treatment might enhance the efficacy of CGT or lead to similar outcomes without CGT.

To determine the effectiveness of citalopram alone or in combination with complicated grief treatment, Katherine Shear, M.D. (pictured above), a professor of psychiatry at the Columbia University College of Physicians and Surgeons, and colleagues randomly assigned 395 bereaved adults who met criteria for complicated grief (defined as 30 points or higher on the Inventory of Complicated Grief [ICG]) to one of four groups: citalopram only (CIT, median dose 40 mg for 12 weeks), placebo only, combined CGT and citalopram treatment, or CGT and placebo treatment. Follow-up assessments took place at 4, 8, 12, 16, and 20 weeks after the first treatment visit and 6 months after study treatment termination.

The authors found patients who received CGT with placebo showed greater improvements than those who received placebo alone (82.5% vs. 54.8%). However, the addition of citalopram was not found to significantly improve CGT outcome (CGT with CIT vs. CGT with placebo: 83.7% vs. 82.5%). However, depressive symptoms decreased significantly more with CGT when CIT was added (CGT with CIT vs. CGT with placebo: Quick Inventory Depressive Symptoms mean difference, −2.06).

“CG is a serious, prevalent, and frequently chronic and debilitating condition that needs to be recognized and treated,” the researchers noted. “Our results support the use of antidepressants in conjunction with CGT for relief of co-occurring depressive symptoms. When CGT is unavailable, CGT-informed supportive clinical management with or without antidepressants may be a helpful approach.”

For related information, see the Psychiatric News article “Progress Being Made at Understanding, Treating Complicated Grief.”

(Photo Courtesy of Columbia University Medical Center)

Study Suggests Appearance Concerns in Males May Predict Depression, Substance Use Risk

Men who express greater concern about their muscularity and leanness may be more likely to experience depression and use drugs, according to a report in the Journal of the Academy of Child and Adolescent Psychiatry. The findings suggest the importance of including cognitive, weight-, and muscularity-focused symptoms as components of assessing the risk of eating disorders in males.

To identify patterns of appearance concerns and eating disorder behaviors from adolescence through young adulthood, the authors analyzed survey data from 7,067 males (aged 9 to 14 at the start of the survey) who completed questionnaires annually from 1996 to 2001 and biennially from 2001 to 2007. Those surveyed were asked to report concerns over muscularity and leanness, as well as eating disorder behaviors (purging, overeating, binge eating, and use of muscle-building products) and health correlates (binge drinking, drug use, and depressive symptoms).

Latent class analyses of observations at ages 13 to 15, 16 to 18, 19 to 22, and 23 to 26 identified one large asymptomatic class and four symptomatic patterns: Body Image Disturbance (high appearance concerns, low eating disorder behaviors); Binge Eating/Purging (binge eating and purging, use of muscle-building products, and low appearance concerns); Mostly Asymptomatic (low levels of muscularity concern, product use, and overeating); and Muscularity Concerns (high muscularity concerns and use of products).

By age 22, 6% of participants were classified to the Body Image Disturbance class, which exhibited high risk for depressive symptoms across adolescence. Relative to the Asymptomatic class, the Muscularity Concerns class had over four times the estimated prevalence of drug use at ages 16 to 18 years, over three times as many participants starting to use drugs at ages 19 to 22 years, and twice as many participants engaged in frequent binge drinking at ages 19 to 22 years.

“Although the classes that emerged differ from similar analyses on female samples, the findings are consistent with research in females indicating that subclinical symptomatic patterns of eating disorder symptoms are also associated with concurrent and incident depressive symptoms and substance use,” the authors wrote.

For related news, see the Psychiatric News article “How to Recognize, Treat Body Dysmorphic Disorder,” by Katharine A. Phillips, M.D.

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Computer Test May Identify Cognitive Impairment Symptoms Following TBI That Other Tests Miss

Cognitive impairment is a common outcome following a traumatic brain injury (TBI), but a thorough cognitive assessment of TBI patients can prove challenging due to the length of cognitive tests, the need for skilled workers to administer the tests, and costs. A report published Friday in the Journal of Neuropsychiatry and Clinical Neurosciences in Advance describes a 10-minute computerized screening tool that may be more accurate at detecting cognitive impairments in people with TBI than other commonly used screening tools.

A total of 255 people aged 14 to 62 attending a TBI clinic were administered the Montreal Cognitive Assessment (MoCA), a brief screening instrument commonly used by clinicians in TBI settings, as well as three computerized tests, which measured executive function, speed of information processing, and working memory (Stroop Test, the Symbol Digit Modalities Test [SDMT], and a visual version of the Paced Auditory Serial Addition Test 2-second trials [PVSAT-2]). Cognitive testing took 20 minutes, with 10 minutes for MoCA and 10 for the computerized battery, and was performed by a research assistant. 

When factoring in age and education level, four patients failed the MoCA test; however, in those with a normal MoCA, 29.5% failed the Stroop, 37.5% the SDMT, and 24.3% the PVSAT-2. Overall, 54.98% failed at least one of the three computer tests. 

Study participants were also given two psychosocial questionnaires—the 28-item General Health Questionnaire (GHQ) and the Rivermead Head Injury Follow-Up Questionnaire (RHIFUQ). The patients who failed the computer tests showed higher rates of psychological distress and anxiety.

“While our computerized screening approach should not be misconstrued as a replacement for detailed cognitive inquiry, it is more sensitive than the MoCA in detecting cognitive compromise and provides clinically useful, rapid results in the absence of a neuropsychological service,” the study authors concluded.

For related information, see the Psychiatric News article “Blood Test May Detect Concussions Days Later” and the Psychiatric Services article “Development and Validation of a Computerized-Adaptive Test for PTSD (P-CAT).”

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Methylphenidate May Increase Risk for Arrhythmias, Myocardial Infarction In Some Youth

Findings from a study published in BMJ Open Access shows that some children and adolescents who are receiving methylphenidate for treatment of attention-deficit/hyperactivity disorder (ADHD) may be at increased risk for certain adverse cardiovascular events.

"Drugs to treat ADHD have been shown to be efficacious in reducing symptoms of impulsivity and hyperactivity in children,” the study authors wrote, "but concerns have been expressed about possible adverse cardiovascular events with the first-line treatment, methylphenidate."

To determine whether an association exists between methylphenidate and adverse cardiovascular events in youth with ADHD, the team of international researchers analyzed insurance claims data submitted by health care providers of 1,224 individuals from South Korea aged 17 and younger who had experienced a cardiovascular event—such as an arrhythmia, myocardial infarction, and ischemic stroke (in accordance with ICD-10 criteria)—and had received at least one prescription for methylphenidate. Incidence of cardiovascular event was adjusted against time on medication and preexisting cardiovascular conditions.

The analysis showed that overall exposure to methylphenidate was significantly associated with an increased risk of arrhythmias, with the highest risk for such events occurring from one to three days after initiation of medication. Risk for arrhythmias was highest in youth who had congenital heart failure.

For myocardial infarction, no increased risk was observed across overall time of exposure to methylphenidate. However, risk for myocardial infarction was significant from eight days to 56 days after initiating treatment. 

No significant increase in risk was observed for hypertension, ischemic stroke, or heart failure. No differences in risks for any outcome were observed between medication doses.

The authors noted, however, that their findings may have been impacted by several study limitations. Among them: Antidepressants, antipsychotics, or antiepileptics are often coprescribed with methylphenidate and could explain some of the association found with cardiovascular adverse events. Also, while the authors adjusted their analyses for time-varying comorbidities and comedications, other confounding factors may have been at play. “For example, there might be differences in severity of ADHD symptoms, substance use, and precipitating factors that could have influenced both the occurrence of a cardiovascular adverse event and methylphenidate exposure,” they wrote.

"The relative risk of myocardial infarction and arrhythmias is increased in the early period after the start of methylphenidate treatment for ADHD in children and young people," the researchers wrote. They concluded that while the absolute risk is likely to be low, the risk-benefit balance of methylphenidate should be carefully considered, particularly in children with mild ADHD.

For related information pertaining to adults, see the American Journal of Psychiatry study "Methylphenidate and Risk of Serious Cardiovascular Events in Adults."

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Patients Treated for Opioid Dependence May Not Be Receiving Proper Treatment After Discharge

As the number of hospitalizations for opioid misuse continues to grow, so too have questions of whether patients have access to medications approved to treat opioid dependence following inpatient treatment. A study published yesterday in Psychiatric Services in Advance suggests that the majority of patients discharged following a hospitalization for opioid misuse are not getting appropriate treatment.

Methadone, naltrexone, and buprenorphine—approved by the FDA for the treatment of opioid dependence—are known to significantly augment treatment retention, decrease illicit opioid use, reduce the burden of opioid craving, and, in some cases, provide relief from opioid-withdrawal symptoms.

To identify patterns of postdischarge prescription fills following a hospitalization for opioid misuse, Sarah Naeger, Ph.D., M.P.H., of the Substance Abuse and Mental Health Services Administration and colleagues analyzed data on individuals hospitalized for opioid abuse, dependence, or overdose contained in the 2010-2014 MarketScan Commercial Claims and Encounters database. Use of FDA-approved medication for the treatment of opioid dependence was defined as a prescription fill for buprenorphine or naltrexone or a paid claim for methadone; the authors also examined prescription fills for antidepressants, antipsychotics, benzodiazepines, and opioid pain medications, such as oxycodone, methadone, morphine, fentanyl, hydrocodone, and tramadol.

Within the database, the authors identified 36,719 patients with an inpatient admission for opioid abuse, dependence, or overdose. Less than a quarter (16.7%) of these patients received any FDA-approved medication for opioid use disorder in the 30 days following discharge. The most commonly filled prescriptions were for antidepressants, received by 40.3% of patients in the sample, followed by opioid pain medication at 22.4%, antipsychotics at 15.6%, and benzodiazepines at 13.9%. Thirty-five percent of the sample did not have any prescription fills in the 30-day postdischarge window.

The low rate of opioid dependence medication and postdischarge use of opioid pain medications and benzodiazepines observed in the study are concerning, the authors wrote: “The finding that 13.9% of patients filled a benzodiazepine prescription, 22.4% filled an opioid prescription, and 7% filled both after an opioid-related hospitalization suggests that targeted outreach to physicians and patients about recommended prescribing practices and the risks associated with the combined use of benzodiazepine and opioid use may be warranted.”

They concluded, “More research is needed to understand the policy, structural, and financial barriers facing patients with an opioid use disorder in trying to access outpatient services that include opioid dependence medication.”

For related information, see the Psychiatric News article “AMA Survey Indicates M.D. Support for Measures to Address Opioid Epidemic.”

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Early-Life Trauma May Predict Antidepressant Response in Adults With MDD

A report in Translational Psychiatry has found that trauma experienced early in life appears to predict poorer treatment outcomes in adults with depression. According to the authors, the findings suggest that screening for childhood trauma may help to identify patients less likely to benefit from standard first-line antidepressants.

The study, which was part of the international Study to Predict Optimized Treatment for Depression (iSPOT-D), enrolled 1,008 adults with major depressive disorder (MDD) in five countries between 2008 and 2012 and compared them with 336 healthy controls. Participants with depression were randomly assigned to receive one of three treatments: escitalopram, sertraline, or venlafaxine-extended release (XR). All participants answered questions about childhood abuse, family breakup, serious personal health events, and experience of disaster.

Patients with MDD experienced more early-life stress than controls and had at least four times the rate of exposure to childhood sexual, physical, or emotional abuse, wrote Leanne Williams, Ph.D., a professor of psychiatry and behavioral sciences at Stanford University School of Medicine, and colleagues.

The authors found that the experience of abuse, especially if it occurred between the ages of four and seven, significantly predicted poorer outcomes. “[P]articipants were about 1.6 times less likely to achieve response or remission if exposed to abuse at this age,” they wrote.

The researchers also found that abuse occurring from age 4 to 7 years was associated with significantly poorer outcomes following treatment with sertraline compared with those taking escitalopram and venlafaxine-XR—a finding the authors noted may be due to sertraline’s known effect on inhibiting dopamine.

“These results suggest that it is important to assess for childhood trauma in the outpatient management of depression, and to consider alternative or supplemental treatments for patients with a trauma history,” the authors concluded. 

For more in Psychiatric News about the relationship between childhood abuse and later psychiatric illness, see “New Study Challenges Assumptions of Child Abuse.”

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