Patients with military-related, chronic posttraumatic stress disorder (PTSD) and symptoms that were not improved with use of an antidepressant medication did not experience a reduction in PTSD symptoms with use of the antipsychotic medication risperidone, according to a study in the August 3 issue of JAMA , a theme issue on violence and human rights.
Posttraumatic stress disorder is among the most common and disabling psychiatric disorders among military personnel serving in combat. Antidepressants are the predominant pharmacotherapy for PTSD, and within the U.S. Department of Veterans Affairs (VA), 89 percent of veterans diagnosed with PTSD and treated with pharmacotherapy are prescribed serotonin reuptake inhibitors (SRIs), according to background information in the article.
“However, SRIs appear to be less effective in men than in women and less effective in chronic PTSD than in acute PTSD. Thus, it may not be surprising that an SRI study in veterans produced negative results. Second-generation antipsychotics (SGAs) are commonly used medications for SRI-resistant PTSD symptoms, despite limited evidence supporting this practice,” the authors write.
John H. Krystal, M.D., of the VA Connecticut Healthcare System, West Haven, Conn., and colleagues evaluated whether risperidone (a second-generation antipsychotic often used for the treatment of schizophrenia and bipolar disorder), when added to an ongoing pharmacotherapy regimen would be more effective than placebo for reducing chronic military-related PTSD symptoms among veterans whose symptoms did not respond to at least 2 adequate SRI treatments. The study consisted of a 6-month, randomized, 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. Patients received risperidone (up to 4 mg once daily) or placebo and other psychosocial mental health therapies. Symptoms of PTSD, depression, anxiety and other health outcomes were gauged via various scales and surveys.
After analysis of the data, the researchers found no statistically significant difference between risperidone and placebo in reducing measures of PTSD symptoms after 6 months of treatment. In addition, risperidone was not statistically superior to placebo on any of the other outcomes, including improvement on measures of quality of life, depression, anxiety, or paranoia/psychosis.
Overall, the rate of adverse events during treatment was low but appeared related to dosing of risperidone.
“In summary, risperidone, the second most widely prescribed second-generation antipsychotic within VA for PTSD and the best data-supported adjunctive pharmacotherapy for PTSD, did not reduce overall PTSD severity, produce global improvement, or increase quality of life in patients with chronic SRI-resistant military-related PTSD symptoms. Overall, the data do not provide strong support for the current widespread prescription of risperidone to patients with chronic SRI-resistant military-related PTSD symptoms, and these findings should stimulate careful review of the benefits of these medications in patients with chronic PTSD,” the authors conclude.
Editorial: Interventions for War-Related Posttraumatic Stress Disorder
In an accompanying editorial  on treating military-related PTSD, Charles W. Hoge, M.D., of the Walter Reed Army Medical Center, Silver Spring, Md., writes that “significant improvements in population care for war veterans will require innovative approaches to increase treatment reach.”
“Attention to the occupational context, combat physiology, and mental and physical comorbidities is essential. Validating and implementing collaborative care models based in primary care should be a high priority. Matching evidence-based components of therapy to patient preferences and reinforcing narrative processes and social connections through peer-to-peer programs are encouraged. Family members, who have their own unique perspectives, are essential participants in the veteran’s healing process and also need their own support. Research is required to better understand the perceptions war veterans have concerning mental health care, acceptability of care, willingness to continue with treatment, and ways to communicate with veterans that validate their experiences as warriors.”
Material adapted from American Medical Association (AMA).
 JAMA. 2011;306:493-502.
 JAMA. 2011;306:549-551.