Friday, February 12, 2016

Buprenorphine-Samidorphan Combination May Reduce Symptoms in Patients With MDD

A small study investigating an adjunctive combination of drugs affecting different opioid receptors demonstrated efficacy in reducing symptoms of depression, according to a paper published today in AJP in Advance.

The study used buprenorphine (a partial µ-opioid receptor agonist that also blocks κ-opioid agonists) and samidorphan (a µ-opioid receptor antagonist), developed by Alkermes, which sponsored the clinical trial. Study participants included 142 people with major depressive disorder (MDD) who had been treated with a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor but had an “inadequate response” to one or two courses of treatment.

The researchers used a two-stage sequential parallel design in which first-round placebo nonresponders were randomized to placebo or high- or low-dosage levels of the drug combination, wrote Maurizio Fava, M.D. (pictured above), a professor of psychiatry at Harvard Medical School and executive vice chair of psychiatry at Massachusetts General Hospital, and colleagues.

Significant improvements in scores on the Hamilton-Depression Rating Scale, the Montgomery-Åsberg Depression Scale, and the Clinical Global Impressions severity scale were recorded among patients taking a 2mg/2mg combination of buprenorphine/samidorphan compared with placebo after four weeks. There was also evidence of improvement in the 8mg/8mg dosage group, although this evidence did not reach statistical significance. Nausea, vomiting, and dizziness were commonly occurring side effects, and there was no evidence of opioid withdrawal or consistent signal of abuse liability, the authors reported.

“These results support the premise of the sequential parallel comparison design as a strategy to enhance signal detection in relatively smaller samples, and they are consistent with the finding that signal detection is enhanced in placebo nonresponders, as the effect size of buprenorphine/samidorphan was greater in stage 2 than in stage 1,” Fava and colleagues wrote. “These results support the hypothesis of a significant role of opioid dysregulation in major depression and the therapeutic potential of opioid modulation,” they concluded.

For more in Psychiatric News about the use of buprenorphine in treating depression, see “Low-Dose Buprenorphine Found to Decrease Suicidal Ideation, but Experts Remain Cautious.”

Thursday, February 11, 2016

Adjunctive Pramipexole May Benefit Patients With Refractory Depression

An article published in the February issue of the American Journal of Psychiatry shows that pramipexole—a selective D3 receptor agonist approved for the treatment of Parkinson’s disease and restless legs syndrome—may be an effective adjunctive therapy for treatment-resistant depression.

Studies have long suggested that agents that enhance dopamine neurotransmission may be particularly useful in reducing treatment-resistant depression. A previous study comparing pramipexole with placebo in an 8-week randomized, double-blind trial with 60 outpatients with major depression for whom at least one adequate antidepressant medication trial (mean, two trials) had failed reported a modest statistically significant benefit of pramipexole (mean= 1.35 mg/day) over placebo, but neither the response rates (40% compared with 33%) nor the remission rates (27% compared with 23%) differed significantly between groups.

For the current treatment series, Jan Fawcett, M.D. (pictured above), a professor of psychiatry at the at the University of New Mexico School of Medicine, and colleagues administered pramipexole (0.25 mg to 5.0 mg/day) to 42 patients aged 25 to 84 with treatment-resistant depression for 2 weeks to 60 months. All patients took pramipexole while maintaining their treatment regimen for depression, which included selective serotonin reuptake receptor inhibitors, tricyclics, and monoamine oxidase inhibitors, as well as electroconvulsive therapy (ECT).

Overall, 76% of the patients showed a meaningful clinical response (achieving remission or a reduction of symptoms), which persisted over a 16-month follow-up period, while 24% were intolerant or nonresponsive to pramipexole. Effective pramipexole dosages ranged from 0.75 mg/day to 5.0 mg/day, with a mean effective dosage of pramipexole in responders and remitters of 2.46 mg/day. Intolerance was encountered early, often at a low dosage and usually due to nausea.

“To our knowledge, this is the first case series of adjunctive pramipexole in patients with treatment-resistant depression,” the authors wrote. They added that although the case series was not a planned study, with patients being managed and evaluated clinically without rating scales or structured interviews, the results “support the notion that pramipexole—and potentially other dopamine agonists—are of value for patients in a treatment-resistant depressive episode. Appropriate precautions, careful patient monitoring, and gradual dosage escalation are advised.”

Pramipexole has not been approved by the Food and Drug Administration for the treatment of depression.

To read more about potential therapies for depression, see the Psychiatric News article “The Ketamine Challenge: When Practice Leaps Ahead of Science.”

(Photo Courtesy of UNMSM)

Wednesday, February 10, 2016

APA Announces Results of 2016 National Election

APA’s Committee of Tellers has approved the following results of APA’s 2016 national election. Please note that these results are considered public, but not official until approved by the Board of Trustees at its meeting on March 19 and 20.

Anita S. Everett, M.D.

Bruce J. Schwartz, M.D.

Trustee at Large
Richard F. Summers, M.D.

Area 3 Trustee
Roger Peele, M.D.

Area 6 Trustee
Melinda L. Young, M.D.

Resident-Fellow Member Trustee-Elect
Uchenna B. Okoye, M.D., M.P.H.

Complete results of the election will be reported in the March 4 issue of Psychiatric News.

Tuesday, February 9, 2016

New Process Announced to Avoid EHR Penalties in 2017; Apply Now

The government has issued an update to previous rules governing the Electronic Health Records Incentive Program and is now allowing blanket “hardship” exemptions to the program so that clinicians, hospitals, and critical access hospitals can avoid penalties that would have been incurred in 2017 had they not complied with “meaningful use” requirements in 2015.

The deadline to apply for the exemption is March 15 for eligible professionals; the deadline for hospitals and critical access hospitals is April 1.

The update, which also reduces the amount of information that eligible professionals, hospitals, and critical access hospitals must submit for an exemption, is the result of the Patient Access and Medicare Protection Act (PAMPA). This law established that the secretary of Health and Human Services may consider hardship exemptions for “categories” of eligible professionals, hospitals, and critical access hospitals. Prior to this law, the Centers for Medicare and Medicaid Services (CMS) was required to review applications on a case-by-case basis. Under the group application, multiple providers and provider types may apply together using a single submission.

This is the first time that an individual may apply for the hardship exemption on behalf of a group of physicians. This individual may be the physician applicant or the individual filling out the information on behalf of a physician group (for example, a member of the group’s administrative staff). CMS will provide notice of its hardship-exception decisions—which are final and cannot be appealed—via the email address provided on the application.

Applying for the hardship will not prevent a physician from earning an incentive; it simply protects a physician from receiving a meaningful-use penalty. Therefore, physicians who believe that they met the requirements for the 2015 reporting period should still apply for the hardship protection.

The update rectifies problems related to CMS’s delayed notification of the meaningful-use rule regarding exemptions; that delay would have adversely impacted many physician practices. The final rule was released last October, which left less than 90 days for physicians to submit data for what should have been a 90-day reporting period before the end of 2015. Because of this delay, the hardship category applies to all physicians.

The new applications and instructions for a hardship exception from the Medicare Electronic Health Records Incentive Program 2017 payment adjustment are posted at the CMS website. For more information, contact APA’s Department of Practice Management and Delivery Systems at

(Image: istockphoto/DragonImages)

Monday, February 8, 2016

Adults Diagnosed With Concussion May Be at Heightened Long-Term Risk of Suicide

Adults who have been diagnosed with a concussion may be at a heightened long-term risk of suicide, reports a study published today in the Canadian Medical Association Journal. According to the authors, the findings suggest that a history of concussion may be relevant when assessing a patient's suicide risk.

Donald Redelmeier, M.D., of Sunnybrook Health Sciences Centre in Toronto and colleagues examined 235,110 records of patients in Ontario who had a concussion between 1992 and 2012. During the follow-up period, 667 suicides occurred, equivalent to 31 deaths per 100,000 patients annually—three times the population norm.

Weekend concussions (considered more likely to be caused by recreational injuries) were associated with a one-third further increased risk of suicide compared with weekday concussions (considered more likely to be caused by occupational injuries). For people with a prior suicide attempt, a psychiatric or substance use disorder, or multiple concussions, this risk was even higher; however, even individuals who met none of these criteria still had double the long-term suicide risk following a concussion.

“[C]oncussions are rarely deemed relevant for consideration by psychiatrists or other physicians when eliciting a patient’s history,” the authors wrote. “Greater attention to the long-term implications of a concussion in community settings might save lives because deaths from suicide can be prevented.”

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Suicide and Chronic Traumatic Encephalopathy.”

(Image: Triff/Shutterstock)

Friday, February 5, 2016

Study Finds Chronic Viral Infections May Contribute to Cognitive Decline

Some chronic viral infections such as herpes could contribute to subtle cognitive deterioration in otherwise healthy older adults, according to a study published in Alzheimer Disease and Associated Disorders.

While previous work had found an association between cognitive problems and viruses, this study offers temporal evidence to suggest infections may contribute to cognitive decline down the road.

Over a period of five years, researchers from the University of Pittsburgh School of Medicine (UPMC) and Johns Hopkins University annually assessed cognitive function (attention, memory, language, and more) in 1,000 adults 65 years and older. At study entry, nonfasting blood samples were obtained and assayed for exposure to cytomegalovirus (CMV), Herpes Simplex virus 1 and 2 (HSV-1, HSV-2), and Toxoplasma gondii (TOX).

The team found that baseline antibody levels for HSV-2 were significantly associated with baseline cognitive scores, while CMV, HSV-2, and TOX (though not HSV-1) were significantly associated with greater cognitive decline over the five-year period—independent of other age-related variables.

“This is important from a public health perspective, as these infections are very common and several options for prevention and treatment are available,” Mary Ganguli, M.D., M.P.H., a professor of psychiatry at UPMC, said in a press statement. “As we learn more about the role that infectious agents play in the brain, we might develop new prevention strategies for cognitive impairment.”

To read more about the potential role of infection in mental health, see the Psychiatric News article “Researchers Consider Infection as One Cause of Depression.”

(Image: Spectral-Design/Shutterstock)

Thursday, February 4, 2016

APA Urges Members to Support Reclassification of ECT Devices

Five years after it last broached the matter, the Food and Drug Administration (FDA) is again proposing to reclassify electroconvulsive therapy (ECT) from a Class III (high risk) medical device to Class II (low risk). APA supports this change.

Opposition from anti-psychiatry groups was blamed for the FDA's maintaining the Class III status in 2011. Opponents to reclassification argued then that ECT causes memory problems, cognitive impairment, and other adverse effects. Supporters noted that current ECT practices, using anesthesia and muscle relaxants, significantly reduce those effects.

The FDA in a recent Federal Register notice acknowledged some side effects but concluded: “FDA believes that in the specified patient population, and with the application of general and special controls as described in this document, the probable benefit to health from use of the device outweighs the probable injury or illness from such use.”

APA urges psychiatrists to contribute their comments to the FDA in favor of the reclassification. A template form letter has been prepared that provides talking points. The FDA’s draft guidance on the proposed reclassification and a link to post comments can be accessed here. The FDA must receive comments by March 28.

“[I]t is so important for psychiatrists to take the lead in expressing their views in regard to the role that ECT plays in clinical practice and in the treatment of major depressive disorder,” wrote APA CEO and Medical Director Saul Levin, M.D., M.P.A., and APA President Renée Binder, M.D., in a blog post. “For appropriate patients, ECT has been a lifesaver. It has given them an opportunity for a normal, functional life.”

For more in Psychiatric News about the previous attempt to reclassify ECT, see “FDA Advisory Panel Favors ECT in High-Risk Category.”


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