Placebo-controlled trial of risperidone augmentation for selective serotonin reuptake inhibitor-resistant civilian posttraumatic stress disorder

Abstract

Objective: Treatment of posttraumatic stress disorder (PTSD) with pharmacotherapy is promising, although the response to medication has generally been modest, and strategies to improve the response to antidepressant medications are needed. The primary objective of this study was to examine risperidone augmentation in civilians with PTSD currently receiving sertraline without an optimal response.

Method: Male and female participants aged 18 to 65 years were recruited from 3 academic medical centers between June 2004 and September 2006. Those who met eligibility criteria with a DSM-IV diagnosis of PTSD subsequent to a civilian trauma and a Clinician-Administered PTSD Scale (CAPS) score greater than or equal to 50 at screen and baseline were entered into phase 1. In phase 1, patients were treated for 8 weeks with open-label sertraline. Those who did not remit (defined as a 70% decrease in PTSD symptoms as measured by the CAPS) were entered into phase 2. In phase 2, patients remained on sertraline and were randomly assigned to augmentation with risperidone or matching pill placebo for 8 weeks. Symptoms of PTSD and depression and psychotic symptoms were measured prospectively throughout the 16-week study.

Results: Of the 45 patients enrolled, 34 completed phase 1, and 25 of those patients were randomly assigned to phase 2; 20 completed phase 2. For all patients across all phases, PTSD and related symptoms improved with no significant differences between groups. In post hoc analyses, the group that received risperidone augmentation had significantly more improvement than the placebo group on the Davidson Trauma Scale (DTS) sleep item (p = .03) and demonstrated a trend toward significantly more improvement on the Clinical Global Impressions-Improvement scale (p = .066), the positive (p = .065) and paranoia (p = .1) subscales of the Positive and Negative Syndrome Scale, and the CAPS sleep item (p = .09).

Conclusion: Participants responded well to sertraline in phase 1, sustained their response, and displayed a placebo response comparable with that of risperidone in phase 2. There is some evidence to support the conclusion that risperidone augmentation was helpful in those subjects who did not remit with sertraline alone, particularly in the areas of global improvement, positive affect, and sleep.

Trial registration: clinicaltrials.gov Identifier: NCT00133822.