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Pharmacotherapy for post-traumatic stress disorder: Systematic review and meta-analysis

  • Mathew Hoskins (a1), Jennifer Pearce (a1), Andrew Bethell (a1), Liliya Dankova (a1), Corrado Barbui (a2), Wietse A. Tol (a3), Mark van Ommeren (a4), Joop de Jong (a5), Soraya Seedat (a6), Hanhui Chen (a7) and Jonathan I. Bisson (a1)...
Abstract
Background

Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy.

Aims

To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability.

Method

A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included.

Results

Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference −0.23, 95% CI −0.33 to −0.12). For individual pharmacological agents compared with placebo in two or more trials, we found small statistically significant evidence of efficacy for fluoxetine, paroxetine and venlafaxine.

Conclusions

Some drugs have a small positive impact on PTSD symptoms and are acceptable. Fluoxetine, paroxetine and venlafaxine may be considered as potential treatments for the disorder. For most drugs there is inadequate evidence regarding efficacy for PTSD, pointing to the need for more research in this area.

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Copyright
Corresponding author
Professor Jonathan I. Bisson, Cardiff University, Institute of Psychological Medicine and Clinical Neurosciences, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff CF24 4HQ, UK. Email bissonji@cf.ac.uk
Footnotes
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The World Health Organization supported this work to inform the development of Mental Health Gap Action Programme (mhGAP) guidelines on disorders and problems specifically related to stress. The views expressed in this article are those of the authors solely and do not necessarily represent the views, policies or decisions of their employers.

Declaration of interest

None.

Footnotes
References
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Pharmacotherapy for post-traumatic stress disorder: Systematic review and meta-analysis

  • Mathew Hoskins (a1), Jennifer Pearce (a1), Andrew Bethell (a1), Liliya Dankova (a1), Corrado Barbui (a2), Wietse A. Tol (a3), Mark van Ommeren (a4), Joop de Jong (a5), Soraya Seedat (a6), Hanhui Chen (a7) and Jonathan I. Bisson (a1)...
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RE: Andrea Cipriani Letter

Mathew Hoskins, Psychiatrist, Cardiff University
Jennifer Pearce, Trainee Clinical Psychologist, Cardiff University
Andrew Bethell, Clinical Studies Officer, Cardiff University
Corrado Barbui, Psychiatrist, University of Verona
Wietse A. Tol, Psychologist, Johns Hopkins Bloomberg School of Public Health
Soraya Seedat, Psychiatrist, Stellenbosch University
Hanhui Chen, Psychiatrist, Shanghai Jiaotong University
Jonathan Bisson, Psychiatrist, Cardiff Univeristy
19 March 2015



Dear Editor,

Professor Cipriani helpfully questions duplication of data from two unpublished studies in our review. We could not get access to the unpublished material for Eli Lilly and Pfizer 589, even after contacting the pharmaceutical companies, and instead relied on the raw data sets obtained from previous reviews.

We have subsequently contacted Dr Friedman who has confirmed that Pfizer 589 was subsequently published as Friedman 2007. We have also contacted the authors of Martenyi 2007, but are, as yet, unable to confirm if this is the published Eli Lilly paper. This seems distinctly possible as the sample sizes are the same but it is important to note that Eli Lilly only released TOP-8 data and not CAPS to the NICE reviewers.

When the Pfizer 589 data is removed it does change the outcome for sertraline, which now demonstrates a small but statistically significant advantage over placebo in reducing the severity of clinician rated PTSD symptoms ((eight studies) n=1271 SMD= -0.16 (95%CI=-0.31 to -0.02) chi squared=33%). This means that paroxetine, fluoxetine, venlafaxine and sertraline can be considered as potential treatments for PTSD.

The outcome for the trauma type subanalysis for sertraline is still statistically insignificant ((three studies) n=278 SMD=-0.42 (95%CI=-1.03 to 0.19) chi squared=81%). Eli Lilly was not included in the meta-analysis of individual agents versus placebo. The overall meta-analysis of SSRIs versus placebo, when Eli Lilly and Pfizer 589 are removed, is now slightly more in favour of SSRIs (nineteen studies) n=3350 SMD= -0.27 (95%CI= -0.37 to -0.16) chi squared =45%; see revised Figure 2 forest plot).

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Conflict of interest: None Declared

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Did you add the same study twice in the meta-analysis?

Andrea Cipriani, Associate Professor
06 February 2015

Dear Editor

I read with interest the systematic review by Mathew Hoskins and colleagues. Looking at Figure 2 of the paper and at the online-only supplemental file, however, it seems to me that two unpublished studies have been counted twice in the meta-analysis. As far as I can see from theinformation reported in the review, the study "Eli Lilly" is the same as "Martenyi 2007" and the study "Pfizer 589" is the same as "Friedman 2007" (same drugs, same comparisons, same sample size). I would be grateful if the authors could clarify the matter.

Bets wishes

Andrea Cipriani

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Conflict of interest: None declared

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