Brain Inflammation Linked to OCD, Study Suggests

Brain inflammation appears to be significantly higher in people with obsessive-compulsive disorder (OCD) than those without the condition, according to a study published this week in JAMA Psychiatry. 

“This finding represents one of the biggest breakthroughs in understanding the biology of OCD, and may lead to novel therapeutic treatments,” senior author Jeffrey H. Meyer, M.D., Ph.D., said in a press release. Meyer is the head of the Neurochemical Imaging Program in Mood and Anxiety at the Centre for Addiction and Mental Health (CAMH) in Toronto. 

A new direction for developing treatments for OCD is welcomed because about one-third of patients with OCD do not adequately respond to current medications, such as antidepressants, according to the authors.

Meyer and colleagues recruited 20 people with OCD and 20 age-matched healthy controls for the study. The participants were all in good physical health, were not taking medications, and were between the ages of 19 and 48. None of the participants had a history of autoimmune disease or neurologic illness or injury. Psychiatric disorders and OCD were confirmed using the Structured Clinical Interview of DSM-IV.

All participants underwent a positron emission tomography (PET) scan, using a fluorine dye to measure a marker of microglial activity in six brain regions (dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex). Activated microglia (immune cells) are known to trigger neuroinflammation.

The researchers found that in people with OCD, inflammation was on average 32% higher in these regions than among those without the condition. 

“To our knowledge, this is the first study demonstrating inflammation within the neurocircuitry of OCD,” Meyer and colleagues wrote. “Although pharmaceutical development does not traditionally prioritize OCD, neuromodulatory treatments under development for other diseases associated with microglial activation, such as Alzheimer disease, might be repurposed toward OCD.” 

For related information, see the Psychiatric News article “Report Highlights Alternative Treatment Options for OCD.”

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APA to Senate: Reject Health Care Reform Proposal That Fails to Put Patients First

APA is urging the Senate to reject the health care reform proposal unveiled today by Senate Republicans. A vote on this bill is expected to come as early as next week, before lawmakers break for the July 4 recess.

The proposed Senate bill rolls back Medicaid expansion, caps federal funding for the Medicaid program, and removes protections for people with pre-existing health conditions. 

“Eliminating requirements for coverage of key benefits, including mental health and substance use disorders and other patient protections that are part of the Affordable Care Act, will have detrimental impacts for millions,” APA President-Elect Altha Stewart, M.D., said in a press release issued by APA today. “Mental health is critical to overall health and needs to be equally accessible.”

Among other provisions, APA opposes changes to Medicaid that would result in the loss of coverage for many Americans, including the estimated 2.8 million with substance use disorders and 1.3 million with serious mental illness, who gained coverage for the first time under the expansion of Medicaid under the current law. The proposed changes to Medicaid could also mean fewer resources for fighting the nation’s opioid epidemic. 

“The Senate proposal represents a significant move in the wrong direction, resulting in fewer people having access to insurance, fewer patient protections, and less coverage for essential behavioral health care,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in the press release. “We urge the Senate to reject this harmful legislation and start again on a health care bill that puts patients first.”

Before the Senate’s proposal was made public, APA expressed significant reservations about how the bill was being drafted without the input of patient and physician groups. In an all-member email sent Monday night, Levin urged members to act. “Mental health and substance use treatment is a bipartisan issue,” Levin wrote. “Over the years, APA has worked with both sides of the aisle to achieve passage of the Mental Health Parity and Addiction Equity Act in 2008, its expansion to cover mental health and substance use disorders as part of the Affordable Care Act in 2010, and the 21st Century Cures Act in 2016.”

The House version of the bill, according to the Congressional Budget Office (CBO), would leave some 14 million more Americans uninsured next year than under the current law and 23 million more uninsured by 2026. The Senate bill awaits CBO analysis.

Your Voice Counts
APA urges you to contact your senators and speak out against the Senate health care reform bill released today. APA has created a dedicated tool to make it easy for you to voice your opinion via Facebook, Twitter, or phone.

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Clonazepam May Reduce Risk of Relapse in Patients With Panic Disorder

While most patients with panic disorder respond to selective serotonin reuptake inhibitors, benzodiazepines, and/or a combination of the two, the risk of relapse after drug discontinuation is known to be high. A study in the Journal of Clinical Psychopharmacology now suggests that patients who take clonazepam may be at a lower risk of relapse than those treated with paroxetine.

The findings were based on an observational, prospective, six-year follow-up study of patients with panic disorder who participated in an open, randomized trial in which they were assigned to take either clonazepam (0.5 mg/d to 2 mg/d) or paroxetine (10 mg/d to 40 mg/d) for eight weeks. Patients who responded to the assigned monotherapy after eight weeks continued this treatment for 34 months; partial or nonresponders were offered a combined treatment with clonazepam and paroxetine. After 34 months in the long-term study, clonazepam and paroxetine were tapered (four months for clonazepam taper, and six weeks for paroxetine taper).

Of the 95 patients who completed the three-year study, 10 failed to achieve remission. The researchers conducted follow-up assessments with the 85 patients who achieved remission at years 1, 2, 3, 5, and 6 following the discontinuation of clonazepam, paroxetine, or a combination of the two. These assessments evaluated the number of panic attacks the patients experienced per month, Clinical Global Impression-Severity (CGI-S) scores, and the 14-item Hamilton Anxiety Rating Scale (HAM-A) scores. (Patients were considered to have relapsed if they were receiving psychotherapy or medication for panic disorder symptoms, had CGI-S scores greater than 1, or had panic attacks in the month preceding the assessment.)

Over the course of the follow-up period, cumulative relapse rates increased from 50% (n=33) at 1 year to 89.4% (n=76) at 6 years. However, one-year relapse rates were lower in patients previously treated with clonazepam (p=0.001) compared with those treated with paroxetine. Similarly, patients treated with clonazepam showed consistently lower relapse rates at 6 years compared with patients who had not taken clonazepam.

According to lead author Rafael C. Freire, M.D., Ph.D., of the Federal University of Rio de Janeiro and colleagues, the study suggests that despite long-term treatment, patients with panic disorder remain at high risk of recurrence when treatment is discontinued. “Treatment with clonazepam appears to protect these patients against relapse, but further studies are needed to support this affirmation,” the authors concluded.

For related information, see the Psychiatric News article “Benzodiazepines: Experts Urge Balance.”

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APA Members Urged to Voice Opposition to Senate Health Bill Today

APA members are urged to contact their U.S. senators to voice opposition to the health care reform bill now being considered in the Senate. Senators are expected to vote on the bill, which is based on the House-passed American Health Care Act (AHCA), by July 4.

The Senate Republican health care overhaul bill would strip 23 million people of their health insurance coverage and cap the Medicaid program—cutting over $880 billion from the program, which is the largest provider of behavioral health services for psychiatric patients. It would also end the guaranteed inclusion of mental health and substance use disorder treatment services in the list of Essential Health Benefits covered under current law.

Members are encouraged to contact their senators by phone, Twitter, or Facebook. A dedicated page on APA’s website will help members make contact with their Senators through these avenues.

In an all-member email delivered last evening, APA CEO and Medical Director Saul Levin, M.D., M.P.A., urged members to act. “Mental health and substance use treatment is a bipartisan issue,” Levin wrote. “Over the years, APA has worked with both sides of the aisle to achieve passage of the Mental Health Parity and Addiction Equity Act in 2008, its expansion to cover mental health and substance use disorders as part of the Affordable Care Act in 2010, and the 21st Century Cures Act in 2016.”

Senate offices track phone messages and respond to social media. “Your calls and action do count,” Levin said. “We ask that you voice opposition to any bill that would negatively impact patients, and we appreciate your standing with us to do what is right for our patients.”

For more information, see the Psychiatric News article “CBO Says Millions of People Could Lose Coverage Under AHCA.”

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Study of Pregnant Publicly Insured Women Finds Increase in SGA Use

The use of second-generation antipsychotics (SGAs) by pregnant women enrolled in Medicaid rose more than threefold between 2001 and 2010, according to a report in Psychiatric Services in Advance. In contrast, the proportion of women who received first-generation antipsychotics (FGA) remained stable over the 10-year period.

“To help clinicians and patients make informed treatment decisions, there is an urgent need for further studies in this area to examine adverse pregnancy outcomes associated with maternal use of antipsychotics, in monotherapy or polytherapy, as well as studies examining comparative effectiveness of specific antipsychotic agents among pregnant women,” Yoonyoung Park, Sc.D., of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital in Boston and colleagues wrote.

Park and colleagues analyzed Medicaid Analytic eXtract (MAX) data (2001–2010) from 1,522,247 pregnancies. MAX contains data on demographic characteristics, hospitalizations, and outpatient visits as well as on medications dispensed by an outpatient pharmacy.

From 2001 to 2010, the number of women who filled at least one prescription for a SGA during pregnancy increased from .4% (n=376) to 1.3% (n=2,044) (p<.001), while the use of FGAs remained stable at about .1%.

The increase in the proportion of women taking SGAs appeared to be driven in part by an increase in quetiapine use, which rose from 0.1% in 2001 to 0.6% in 2010, and aripiprazole, which was introduced in 2002 and was used by 0.4% of women by 2010, the authors noted. 

During the study period, the prevalence of bipolar disorder diagnosis in pregnant women also increased more than threefold (from .7% to 2.5%), while the proportion of pregnant women with bipolar disorder who received antipsychotics increased from 13.6% in 2001 to 23.6% by 2010. The authors noted that the increase in bipolar disorder diagnoses is “consistent with the increase observed for the general population, including children and adolescents.”

Additionally, among the 15,196 women who took antipsychotics at any time during pregnancy, 65.2% also received antidepressants, 24.9% received benzodiazepines, and 22.0% received mood stabilizers; 765 women (5%) received at least one prescription for all four of these drug types at some point during pregnancy.

“Polytherapy with other psychotropic medications, common in this population, deserves more attention with regard to fetal safety,” Park and colleagues wrote. “Because Medicaid pays for close to 50% of all deliveries of babies in the United States, the results reflect the real-world utilization of antipsychotics in a large proportion of pregnant women in the U.S. population.” 

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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New Drug Shows Promising Results in Treatment of Postpartum Depression

In a small sample of women with severe postpartum depression, infusion of the compound brexanolone resulted in rapid, significant reduction in symptoms, according to a study published online this week in The Lancet.

The findings “demonstrate a substantial treatment effect of brexanolone” in a group of patients “for which there are no currently approved pharmacological therapies,” Steven Kanes, M.D., of Sage Therapeutics and colleagues wrote. Sage Therapeutics funded this research, and assisted in the study design, data collection, data analysis, data interpretation and writing of the report.

For the double-blind, randomized, controlled trial, the researchers assigned 21 women with severe postpartum depression (Hamilton Depression Rating Scale [HAM-D] score of at least 26) to a 60-hour, continuous intravenous dose of brexanolone or placebo. To make the sample as representative as possible, the researchers recruited patients from urban, suburban, and rural settings in the United States to receive treatment at four research sites.

By 60 hours, seven (70%) women had achieved remission (HAM-D total score of ≤7) compared to one (9%) in the placebo group. Furthermore, mean HAM-D scores for the women who received brexanolone remained significantly lower for a follow-up period of 30 days compared with the placebo group.

Brexanolone is an allosteric modulator of both synaptic and extra-synaptic GABA-A receptors. The results support the rationale for targeting GABA-A receptors in the development of therapies for the estimated 10% to 20% of birth mothers who suffer from postpartum depression, wrote the researchers.

“Our findings provide the first placebo-controlled clinical support for the role of extrasynaptic GABA-A receptors in the modulation of mood and affective states in any clinical population,” wrote the authors. A treatment with rapid onset of action is considered important in severe postpartum depression because of the adverse impact of the depression on the mother, infant, and family.

Brexanolone, a formulation of the neuroactive steroid allopregnanolone, was found to be generally well tolerated among the study participants. There were no deaths, serious adverse events, or discontinuations. The most commonly reported adverse events in the brexanolone group were dizziness (two brexanolone-treated subjects; three placebo-treated subjects) and somnolence (two brexanolone-treated subjects; no placebo-treated subjects).

The author of an accompanying commentary published in The Lancet commented on the study’s “potentially important implication for our understanding of the pathophysiology of postpartum mood disorders,” but he also raised questions such as “Is this a treatment for postpartum episodes specifically or could it be used generally in depression?”

Brexanolone is currently being evaluated in a phase 3 clinical program under way at various other sites across the country.

For related information, see the Psychiatric News article “Synthetic Oxytocin May Increase Risk of Postpartum Depression, Anxiety” and the Psychiatric Services article “Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.”

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APA Urges Senate to Be Transparent, Inclusive in Crafting ACA Repeal Bill

APA today joined with five other medical associations to raise concerns about how the Senate is developing legislation that would harm patients by repealing and undermining essential health care coverage and patient protections established by the Affordable Care Act (ACA). 

In a letter to Senate Majority Leader Mitch McConnell (R-Ky.) and Senate Minority Leader Charles Schumer (D-N.Y.), the six medical organizations urged the political leaders to “commit to a transparent, deliberate, and accountable process” that allows adequate time for stakeholders to provide input on the impact the proposed legislation would have on patients and their physicians. The letter also calls for public hearings on the proposed bill as well as sufficient time to ensure that the Senate has the Congressional Budget Office (CBO) score on the legislation and other independent analyses available for review well in advance of any vote.

“Proposed legislation revamping our nation’s health care system needs to be worked on in the open, not behind closed doors,” APA President-Elect Altha Stewart, M.D., said in a news release. “We are determined that the voices of patients with mental illness or substance use disorders be heard.”  

The five groups that signed onto the letter with APA were the American Academy of Family Physicians, American College of Physicians, American Osteopathic Association, American Academy of Pediatrics, and the American Congress of Obstetricians and Gynecologists. These groups collectively represent more than 560,000 physicians and medical students. 

APA was part of the same coalition of medical organizations that had expressed strong opposition to the American Health Care Act (AHCA), which the House of Representatives passed on May 4. 

Late last month, the CBO released its score of the AHCA, which it projected would leave some 14 million more Americans uninsured next year than under the current law and 23 million more uninsured by 2026. APA had responded to the news immediately at the time, renewing its call for the Senate to reject the ACA replacement bill in favor of a bipartisan solution. 

This week, APA CEO and Medical Director Saul Levin, M.D., M.P.A., reiterated that message. “We are willing to work with lawmakers on both sides of the aisle in crafting health care legislation that provides adequate coverage to Americans,” he said in a news release. “Allow us to lend our expertise to this important issue. It is crucial that any legislation include mental health and substance use disorder treatment.”

(Image: Mikhail Kolesnikov/Shutterstock)