Augmentation of antidepressants with perospirone for treatment-resistant major depressive disorder

Abstract

We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. Twelve patients with major depressive disorder and an incomplete or no response to different kinds of antidepressants (selective serotonin reuptake inhibitor, milnacipran, or sulpride) monotherapy or polytherapy for 8 weeks or more were treated with perospirone augmentation in an eight-week, open-label study. Data were gathered from July 2006 to March 2008. The mean duration of antidepressant pharmacotherapy at baseline was 28 weeks. At baseline, the mean (± SD) of the MADRS scores was 35.8 ± 10.1. The mean (± SD) initial dose of perospirone was 7.0 ± 2.9 mg/day and the final dose was 11.7 ± 6.6 mg/day. Significant reductions in MADRS scores were observed at weeks 2, 4, 6 and 8. Although two of the twelve subjects who completed the protocol achieved remission by the study endpoint, five of the twelve patients were responders (i.e., > 50% improvement in the MADRS score). Sleepiness and tremor were observed in six patients and one patient, respectively, resulting in a reduction of perospirone dose due to these side effects. The discontinuation rate after 8 weeks of treatment was zero. These findings suggest that perospirone may be an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical evidence, a double-blind, placebo-controlled trial is warranted.