Andrea Cipriani1, Taryn Williams2, Adriani Nikolakopoulou3, Georgia Salanti3, Anna Chaimani4, Jonathan Ipser2, Phil J Cowen1, John R Geddes1, Dan J Stein2. 1. Department of Psychiatry,University of Oxford,UK. 2. Department of Psychiatry and Mental Health and Medical Research Council of South Africa Unit on Anxiety & Stress Disorders,University of Cape Town,South Africa. 3. Department of Clinical Research,Institute of Social and Preventive Medicine,University of Bern,Switzerland. 4. Department of Hygiene and Epidemiology,University of Ioannina School of Medicine,Greece.
Abstract
BACKGROUND: Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds. METHODS: Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up. RESULTS: Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72-32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking. CONCLUSIONS: The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.
BACKGROUND: Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds. METHODS: Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up. RESULTS:Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72-32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking. CONCLUSIONS: The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.
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