Pharmacotherapy for post-traumatic stress disorder - a systematic review and meta-analysis

Abstract

Background. Post-traumatic stress disorder (PTSD) is a prevalent and disabling condition. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in use of medication in its treatment. Objectives. To assess the effects of medication in the treatment of PTSD. Design. Systematic review of randomised controlled trials (RCTs) following the Cochrane Collaboration guidelines. A more detailed version of the review is published in the Cochrane Database of Systematic Reviews. Methods. We searched the Cochrane Depression, Anxiety and Neurosis Group specialised register, the Cochrane Central Register of Controlled Trials (Cochrane Library issue 4, 2004), MEDLINE (January 1966 - December 2004), PsycINFO (1966 - 2004), the National PTSD Center Pilots database, and the meta register module of the Controlled Trials database. Reference lists of retrieved articles were searched for additional studies. Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin re-uptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were done. Main results. Thirty-five short-term (14 weeks or less) RCTs were included in the analysis (4 597 participants). Symptom severity for 17 trials was significantly reduced in the medication groups, relative to placebo (weighted mean difference (WMD) = −5.76, 95% confidence interval (CI): −8.16 - −3.36, N = 2 507). Similarly, summary statistics for responder status from 13 trials demonstrated overall superiority of a variety of medication agents compared with placebo (relative risk (RR) = 1.49, 95% CI: 1.28, 1.73, number needed to treat (NNT) = 4.85, N = 1 272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5% (N = 628) of patients, respectively. Of the medication classes, evidence of treatment efficacy was most convincing for the SSRIs. Medication was also effective in reducing the severity of the PTSD re-experiencing/intrusion, avoidance/numbing, and hyperarousal symptom clusters in 9 trials (N = 1 304). In addition, medication was superior to placebo in reducing comorbid depression and disability. Medication was also less well tolerated than placebo. A narrative review of the 3 maintenance trials suggested that long-term medication may be required in treating PTSD.Conclusion. Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability, and should be considered as part of the treatment of this disorder. The findings of this review support the status of SSRIs as first-line agents in the pharmacotherapy of PTSD, as well as their value in longterm treatment. However, there remain important gaps in the evidence base, and there is a continued need for more effective agents in the management of PTSD.