{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:24:46Z","timestamp":1793211886335,"version":"4.5.0"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2011,8,3]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Serotonin reuptake-inhibiting (SRI) antidepressants are the only FDA-approved pharmacotherapies for the treatment of posttraumatic stress disorder (PTSD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Risperidone (up to 4 mg once daily) or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Change in CAPS scores from baseline to 24 weeks in the risperidone group was \u221216.3 (95% CI, \u221219.7 to \u221212.9) and in the placebo group, \u221212.5 (95% CI, \u221215.7 to \u22129.4); the mean difference was 3.74 (95% CI, \u22120.86 to 8.35; <jats:italic>t<\/jats:italic>\u00a0=\u00a01.6; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.11). 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, \u22120.74 to 6.20; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.12). Risperidone did not reduce symptoms of depression (MADRS mean difference, 1.19; 95% CI, \u22120.29 to 2.68; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.11) or anxiety (HAMA mean difference, 1.16; 95% CI, \u22120.18 to 2.51; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.09; patient-rated CGI mean difference, 0.20; 95% CI, \u22120.06 to 0.45; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to 0.34; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.04), or increase quality of life (SF-36V physical component mean difference, \u22121.13, 95% CI, \u22122.58 to 0.32; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.13; SF-36V mental component mean difference, \u22120.26; 95% CI, \u22122.13 to 1.61; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.79). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Among patients with military-related PTSD with SRI-resistant symptoms, 6-month treatment with risperidone compared with placebo did not reduce PTSD symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>clinicaltrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" 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