[Intervention Review]
Pharmacotherapy for post traumatic stress disorder (PTSD)

Dan J Stein1, Jonathan C Ipser2, Soraya Seedat2

1Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. 2MRC Research Unit for Anxiety and Stress Disorders, University of Stellenbosch, Tygerberg, South Africa

Contact address: Dan J Stein, Department of Psychiatry and Mental Health, University of Cape Town, Anzio Road, Rondebosch, Cape Town, 7700, South Africa. dan.stein@uct.ac.za. djs2@sun.ac.za. (Editorial group: Cochrane Depression, Anxiety and Neurosis Group.)

Cochrane Database of Systematic Reviews, Issue 4, 2009 (Status in this issue: Unchanged)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD002795.pub2
This version first published online: 25 January 2006 in Issue 1, 2006. Last assessed as up-to-date: 13 October 2005. (Help document - Dates and Statuses explained).

This record should be cited as: Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD002795. DOI: 10.1002/14651858.CD002795.pub2.
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Abstract

Background
Post traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.

Objectives
To assess the effects of medication for post traumatic stress disorder.

Search strategy
We searched the Cochrane Depression, Anxiety and Neurosis Group specialised register (CCDANCTR-Studies) on 18 August 2005, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 4, 2004), MEDLINE (January 1966 to December 2004), PsycINFO (1966 to 2004), and the National PTSD Center Pilots database. Reference lists of retrieved articles were searched for additional studies.

Selection criteria
All randomised controlled trials (RCTs) of pharmacotherapy for PTSD.

Data collection and analysis
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 reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken.

Main results
35 short-term (14 weeks or less) RCTs were included in the analysis (4597 participants). Symptom severity for 17 trials was significantly reduced in the medication groups, relative to placebo (weighted mean difference -5.76, 95% confidence intervals (CI) -8.16 to -3.36, number of participants (N) = 2507). Similarly, summary statistics for responder status from 13 trials demonstrated overall superiority of a variety of medication agents to placebo (relative risk 1.49, 95% CI 1.28 to 1.73, number needed to treat = 4.85, 95% CI 3.85 to 6.25, N = 1272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5% (628) of patients, respectively. Of the medication classes, evidence of treatment efficacy was most convincing for the SSRIs.

Medication was superior to placebo in reducing the severity of PTSD symptom clusters, comorbid depression and disability. Medication was also less well tolerated than placebo. A narrative review of 3 maintenance trials suggested that long term medication may be required in treating PTSD.

Authors' conclusions
Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability. 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 long-term treatment. However, there remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

Plain language summary

Medication for post traumatic stress disorder
Post traumatic stress disorder (PTSD) occurs after exposure to significant trauma and results in enormous personal and societal costs. Although traditionally treated with psychotherapy, there is increasing recognition of a theoretical basis for medication treatments. This was a systematic review of 35 short-term randomised controlled trials of pharmacotherapy for PTSD (4597 participants). A significantly larger proportion of patients responded to medication (59.1%) than to placebo (38.5%) (13 trials, 1272 participants). Symptom severity was significantly reduced in 17 trials (2507 participants). The largest trials showing efficacy were of the selective serotonin reuptake inhibitors, with long-term efficacy also observed for these medications.

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