Pharmacotherapy for posttraumatic stress disorder

D J Stein, N Zungu-Dirwayi, van Der Linden GJ, S Seedat
Cochrane Database of Systematic Reviews 2000, (4): CD002795

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. By definition prior psychological trauma plays a causal role in the disorder, and psychotherapy is a widely accepted intervention. Nevertheless there is growing evidence that PTSD is characterized by specific psychobiological dysfunctions, and this has contributed to a growing interest in the use of medication in its treatment.

OBJECTIVES: The authors aimed to undertake a systematic review of randomized controlled trials (RCTs) of the pharmacotherapy of posttraumatic stress disorder (PTSD) following the guidelines and using the software of the Cochrane Collaboration, and to provide an estimate of the effects of medication in this disorder. Secondary objectives were to explore questions about whether particular classes of medication are more effective and/or acceptable than others in the treatment of PTSD, and about which factors (clinical and methodological) predict response to pharmacotherapy.

SEARCH STRATEGY: Studies of the pharmacotherapy of PTSD were identified using literature searches of MEDLINE (1966 to 1999, using the textwords posttraumatic, post-traumatic, medication, pharmacotherapy) and other electronic databases (PSYCLIT; National PTSD Center Pilots database; Dissertation Abstracts; Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register). In addition, published and unpublished RCTs were requested from PTSD researchers and pharmaceutical companies. An initial broad strategy was undertaken to find not only RCTs, but also open-label trials and reviews of the pharmacotherapy of PTSD; additional studies were sought in reference lists of retrieved articles and included studies in any language.

SELECTION CRITERIA: All RCTs of PTSD (including both placebo controlled and comparative trials), whether published or unpublished, but completed prior to the end of 1999 were considered for the review.

DATA COLLECTION AND ANALYSIS: Selected RCTs were independently assessed and collated by 2 raters, and Review Manager (RevMan) software was used to capture data on treatment response and PTSD symptom ratings. Ratings of subtypes of PTSD symptoms (intrusive/re-experiencing, avoidant/numbing, hyperarousal), of comorbid symptoms (depression, anxiety), and of quality of life were included where possible. A range of additional information, which may explain possible clinical and methodological heterogeneity amongst the trials, was also captured. Summary statistics for dichotomous and continous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken.

MAIN RESULTS: 15 short-term (12 weeks or less) RCTs were found, of which 9 had sufficient data for inclusion in the analysis. Methodological limitations were particularly apparent in early work; these included short (5 weeks or less) duration of trials and a reliance on self-report scales (rather than use of standardized clinician-rated scales). Despite these and other potentially important differences between the trials, many trials demonstrated efficacy for medication over placebo. Summary statistics were calculated for the Clinical Global Impressions scale change item (CGI-C) or close equivalent from 10 sets of data including various antidepressants and other agents - the proportion of non-responders was lower in the pharmacotherapy group than in the control group (relative risk (95% CI) = 0.72 (0.64, 0.83)). Similarly, summary statistics for the intrusion, avoidance and total scales of the Impact of Events Scale (IES) from 4sets of data again including various agents showed a statistically (and clinically) significant difference between medication and placebo (Weighted Mean Difference (95% CI) = -3.81 (-6.72,-0.91), -3.31(-5.24,-1.37), -7.18 (-11.86,-2.50) respectively).

REVIEWER'S CONCLUSIONS: Medication treatments can be effective in PTSD, acting to reduce its core symptoms, and should be considered as part of the treatment of this disorder. The existing evidence base does not provide sufficient data to suggest particular predictors of response to treatment, or to demonstrate that any particular class of medication is more effective or better tolerated than any other. However, the largest trials showing efficacy to date have been with the SSRIs, and in contrast, there have been negative studies of some agents. Given the high prevalence and enormous personal and societal costs of PTSD, there is a need for additional controlled trials in this area. Additional questions for future research include the effects of medication on quality of life in PTSD, appropriate dose and duration of medication, the use of medication in different trauma groups, in pediatric and geriatric subjects, and the value of early (prophylactic), combined (with psychotherapy), and long-term (maintenance) medication treatment.

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