Jeffrey Goltz, M.D.

SSRIs are the first line pharmacological treatment for PTSD.  However, the response rate with SSRIs alone is typically <60%, with between 20-40% of patients achieving full remission.   Thus, many PTSD patients either have residual symptoms or are resistant to treatment with SSRIs.  This article will briefly review evidence for use of antipsychotic medication to help pharmacologically treat PTSD.

A variety of studies have been conducted to assess the efficacy of using antipsychotic medications for the treatment of PTSD.  The Clinician Administered PTSD Scale (CAPS) is often used to measure the effectiveness of a medication for reducing PTSD symptoms.The three subcategories of the scale include: intrusion, avoidance/numbing, and hyperarousal. The two best-studied antipsychotics treatment of PTSD are Risperidone and Olanzapine.  Wang, Woo, & Bahk (2013) analyzed available data for double-blind, placebo randomized-control trials (RCTs) dating up until January 2013. Most of these studies were conducted on  < 100 patients and produced mixed results.  The largest RCT (247 subjects) for evaluating antipsychotic effectiveness demonstrated that Risperidone had no effect as an adjunct for reducing total CAPS scores (Krystal et al., 2011).  While it did have some effect on the reduction intrusion and hyperarousal scores, the effect size was likely subclinical.  Also, no difference in quality of life was found when Risperidone was added to the regimen.

Similarly, RCTs with other antipsychotic medications used as a monotherapy have failed to establish the utility of these drugs in the treatment of PTSD.  In one case, an RCT initiated using Ziprasidone was stopped prematurely due to adverse side effects.  Also, an RCT (n=15) using Aripiprazole as a monotherapy (Naylor et al., 2015) has also shown no statistically significant effect on PTSD symptoms.   The only evidence for efficacy of Aripiprazole and Quetiapine (no RCTs known to author) comes from case studies, uncontrolled trials, or retrospective studies (Wang et al., 2013).

On the other hand, a number of meta-analyses have demonstrated a statistically significant effect of antipsychotics on total CAPS scores, including that done by Han et al. (2014). However, the effect size obtained by Han et al. indicates a minor clinical effect.  Other meta-analyses have similarly shown minor reductions in total CAPS scores (Liu, Xie, Wang, & Cui, 2014).

Therefore, the strength of studies performed to evaluate the efficacy of antipsychotic drugs for the treatment of PTSD has been limited by the small sample size and the short length of the studies (most less than 2 months).   In addition, most RCTs with antipsychotics have only been done with either Risperidone or Olanzapine and are difficult to compare and assess because of the variability of their use either as an adjunct to SSRIs, or as a monotherapy.  Also, the results from RCTs are mixed.  Further, while there may be some improvement with antipsychotics, it is important to recall that the side effects produced by antipsychotics may negatively effect patients’ quality of life (i.e., weight gain).  A small gain may be exchanged for worsening physical health consequences.  Larger studies are needed to better evaluate antipsychotics.  

Works Cited and Recommended Reading

Han, C., Pae, C., Wang, S., Lee, S.,  Patkar, A.A., Masand, P.S. & Serretti, A. (2014). The potential role of 
atypical antipsychotics for the treatment of posttraumatic stress disorder.  Journal of Psychiatric Research,  72, 72-81.

Krystal, J.H., Rosenheck, R.A., Cramer, J.A., Vessicchio, J.C., Jones, K.M., Vertrees, J.E., … Stock, C. (2011).  Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial.  The Journal of the American Medical Association (JAMA), 306(5), 493-502.

Liu, X., Xie, X., Wang, K., & Cui, H. (2014).  Efficacy and acceptability of atypical antipsychotics for the treatment of post-traumatic stress disorder: a meta-analysis of randomized, double-blind, placebo-controlled trials.  Psychiatry Research, 219(3), 543-549

Naylor, J.C., Kilts, J.D., Bradford, D.W., Strauss, J.L., Capehart, B.P, Szabo, S.T., … Marx, C.E. (2015).  A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military veterans resistant to antidepressant treatment.  Introduction to Clinical Psychopharmacology, 30(3), 167-174.

Wang, H.R, Woo, Y.S. & Bahk, W. (2013)  Atypical antipsychotics in the treatment of PTSD.  Clinical Neuropharmacology, 36(6), 216-222.