Mirtazapine not efficacious as PTSD monotherapy

Mirtazapine monotherapy did not appear efficacious for treating PTSD, according to results of a randomized, placebo-controlled trial published in Journal of Clinical Psychiatry.

“Four open-label and [three] controlled trials suggest that mirtazapine is beneficial in the treatment of PTSD, an effect size of 0.27,” Lori L. Davis, MD, of the Research and Development Service at VA Medical Center in Alabama, and colleagues wrote. “However, most of these studies were limited by small sample size, selective outcome reporting and open-label design.”

The investigators sought to assess the efficacy of mirtazapine, a tetracyclic antidepressant, as PTSD monotherapy treatment among U.S. military veterans with PTSD according to DSM-4 criteria. They randomly assigned 39 participants to placebo and 39 to mirtazapine titrated up to 45 mg per day for a double-blind period of 8 weeks, followed by 8 weeks of an open-label phase of mirtazapine treatment. The Structured Interview for Posttraumatic Stress Disorder (SIP) served as the primary outcome efficacy measures. Other measures of PTSD, depression and sleep served as secondary measures. The researchers used mixed-model procedures with a random intercept to conduct analyses of treatment groups, which were meant to test whether mirtazapine was more effective than placebo in reducing PSTD and depression symptoms, as well as in improving quality of sleep.

Davis and colleagues observed no significant differences between groups on SIP scores during the controlled phase. However, they noted significant improvements in secondary outcomes according to the Clinical Global Impressions-Improvement scale for the mirtazapine group vs. the placebo group. Further, there was significant symptom improvement in SIP total score and in scores on the SIP re-experiencing, avoidance and hyperarousal subscales during the 8-week open-label phase. The researchers observed no significant differences between groups in the occurrence of adverse events.

“Our results do not rule out the possibility of mirtazapine as an effective adjunctive treatment to other psychotropic medications or psychotherapy in the treatment of PTSD,” Davis and colleagues wrote. “Identifying the best path of treatment for PTSD has proven to be difficult, yet it remains an essential and imperative task for researchers.”