Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service-Related PTSD A Randomized Trial

Context Serotonin reuptake-inhibiting (SRI) antidepressants are the only FDA-approved pharmacotherapies for the treatment of posttraumatic stress disorder (PTSD). Objective To determine efficacy of the second-generation antipsychotic risperidone as an adjunct to ongoing pharmacologic and psychosocial treatments for veterans with chronic military-related PTSD. Design, Setting, and Participants A 6-month, randomized, double-blind, placebo-controlled multicenter trial conducted between February 2007 and February 2010 at 23 Veterans Administration outpatient medical centers. Of the 367 patients screened, 296 were diagnosed with military-related PTSD and had ongoing symptoms despite at least 2 adequate SRI treatments, and 247 contributed to analysis of the primary outcome measure. Intervention Risperidone (up to 4 mg once daily) or placebo. Main Outcome Measures The Clinician-Administered PTSD Scale (CAPS) (range, 0-136). Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAMA), Clinical Global Impression scale (CGI), and Veterans RAND 36-Item Health Survey (SF-36V). Results Change in CAPS scores from baseline to 24 weeks in the risperidone group was -16.3(95% CI, -19.7 to -12.9) and in the placebo group, -12.5(95% CI, -15.7 to -9.4); the mean difference was 3.74(95% CI, -0.86 to 8.35; t=1.6; P=.11). Mixed model analysis of all time points also showed no significant difference in CAPS score (risperidone: mean, 64.43; 95% CI, 61.98 to 66.89, vs placebo: mean, 67.16; 95% CI, 64.71 to 69.62; mean difference, 2.73; 95% CI, -0.74 to 6.20; P=.12). Risperidone did not reduce symptoms of depression (MADRS mean difference, 1.19; 95% CI, -0.29 to 2.68; P=.11) or anxiety (HAMA mean difference, 1.16; 95% CI, -0.18 to 2.51; P=.09; patient-rated CGI mean difference, 0.20; 95% CI, -0.06 to 0.45; P=.14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to 0.34; P=.04), or increase quality of life (SF-36V physical component mean difference, -1.13, 95% CI, -2.58 to 0.32; P=.13; SF-36V mental component mean difference, -0.26; 95% CI, -2.13 to 1.61; P=.79). Adverse events were more common with risperidone vs placebo, including self-reported weight gain(15.3% vs 2.3%), fatigue(13.7% vs 0.0%), somnolence (9.9% vs 1.5%), and hypersalivation (9.9% vs 0.8%), respectively. Conclusion Among patients with military-related PTSD with SRI-resistant symptoms, 6-month treatment with risperidone compared with placebo did not reduce PTSD symptoms.