Drug & Device Development

Prophylactic antidepressant may ward off interferon blues

Last Updated: 2012-07-16 17:00:28 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - Preemptive antidepressants can reduce the incidence and severity of depression associated with pegylated interferon therapy in adults without a history of psychiatric disorders, according to a multicenter study from Germany.

"It has been shown that a pretreatment with antidepressants (especially SSRIs) is helpful for patients suffering from depressive mood changes when antiviral treatment with IFN-alpha is started," Dr. Martin Schaefer from Kliniken Essen-Mitte noted in an email to Reuters Health.

"However, our trial for the first time shows, that in every patient, especially patients without any psychiatric problems, depressive mood changes as side effects from interferon can be reduced or prevented with escitalopram," he added.

The findings are "highly relevant for improving and optimizing the safety and tolerability of IFN-alpha treatment," the authors write in a paper online July 16 in Annals of Internal Medicine.

Dr. Sanjeev Sockalingam, from the Hepatology and Mental Health Service, University Health Network, and Department of Psychiatry, University of Toronto, Canada, who was not involved in the study, agrees.

In an email to Reuters Health, he noted that although there have been recent advances in therapy for hepatitis C, specifically the addition of direct acting antivirals, pegylated interferon-alpha remains the mainstay of treatment.

"Concerns about interferon-induced neuropsychiatric side effects, specifically depression, have plagued hepatitis C treatment and limited its widespread use," he said. "Rates of interferon-induced depression approximate 20% to 30% in hepatitis C patients without a significant psychiatric history and untreated depression can lead to potentially fatal, albeit rare, outcomes such as suicide in this population."

Several groups have tried to study antidepressant pretreatment in the context of hepatitis C therapy, but according to Dr. Sockalingam their findings "have been inconclusive and limited by lack of statistical power, use of concomitant psychotropic agents and short study duration."

"I applaud the authors (of the current study) for pursuing a more definitive answer about the role of prophylactic antidepressant treatment during hepatitis C therapy," he added.

Dr. Schaefer and colleagues enrolled 181 HCV-infected patients without a history of psychiatric illness from 10 university and 11 academic hospitals in Germany. They randomly assigned 90 to escitalopram 10 mg per day and the remaining 91 to placebo - started two weeks before and continuing for 24 to 48 weeks of antiviral therapy with PEG-IFN-apha2a plus ribavirin.

Far fewer patients in the antidepressant arm developed depression, defined as a MADRS (Montgomery-Asberg Depression Rating Scale) score of 13 or higher: 25 patients (32%) vs 49 (59%) with placebo. The absolute difference of 27 percentage points was significant (p<0.001).

Major depression was diagnosed in seven patients (8%) taking the antidepressant compared with 17 (19%) taking placebo (p=0.031).

"Response to antiviral therapy was not negatively influenced by antidepressant pretreatment," Dr. Schaefer told Reuters Health by email. Fifty patients (56%) in the antidepressant arm and 42 (46%) in the placebo arm achieved a sustained virologic response (p=0.21).

This finding corroborates reports from other trials showing "good safety and tolerability of antidepressants in patients with HCV infection during antiviral therapy," the researchers note in their paper.

Dr. Sockalingam told Reuters Health that the "promising results from this well designed study suggest that there may be role for antidepressant pre-treatment in preventing interferon-associated depression."

"Although studies have shown that psychiatric patient populations, including patients with mood disorders, can successfully be treated for hepatitis C, this evidence has been conducted in multidisciplinary settings with access to psychiatric support," he added. "Most hepatitis C treatment clinics are limited in terms of psychiatric resources, a clinical reality that has fueled research on prophylactic antidepressant treatment for interferon-induced depression."

The German study, Dr. Sockalingam continued, is "the first step in answering this important question and may prove to be an answer to the paucity of psychiatric support available for most patients on interferon-alpha therapy. Future studies with comparable study design are needed to build on these findings and should specifically explore the role of prophylactic antidepressant therapy in the larger hepatitis C patient population with co-morbid psychiatric illness."

Roche Pharma and Lundbeck provided the primary funding for the study.

SOURCE: http://bit.ly/OJWdyv

Ann Intern Med 2012.