Pharmacological treatments for adults with post-traumatic stress disorder: A network meta-analysis of comparative efficacy and acceptability

Background: The purpose of this study was to compare efficacy and acceptability among drug treatments for adults with post-traumatic stress disorder (PTSD) through a systematic review, random-effects pairwise and network meta-analyses. Methods: Double-blind randomized controlled trials comparing pharmacological interventions for adults with PTSD were searched from database inception through Aug. 28, 2018, on Cochrane (Central), Embase, LILACS, PILOTS, PsycINFO, PubMed, and Web of Science. Clinical trial registries and the websites of pharmaceutical companies were also searched. The GRADE system was used to assess the quality of the evidence. Results: The systematic review included 58 studies comprising 6766 patients randomized to 26 different interventions. Regarding efficacy, topiramate (SMD = -0.57; 95%CrI: -1.07,-0.10), risperidone (SMD = -0.53; 95% CrI: -0.93,-0.15), quetiapine (SMD = -0.59; 95%CrI: -1.06,-0.11), paroxetine (SMD = -0.35; 95%CrI: -0.48,-0.21), venlafaxine (SMD = -0.25; 95%CrI: -0.44,-0.05), fluoxetine (SMD = -0.28; 95%CrI: -0.46,-0.08), and sertraline (SMD = -0.21; 95%CrI: -0.33,-0.09) outperformed placebo. Moreover, phenelzine (RR = 3.39; 95%CrI: 1.43,11.09), lamotrigine (RR = 4.39; 95%CrI: 1.18,26.38), and fluoxetine (RR = 1.28%CrI: 1.01,1.59) outperformed placebo in terms of acceptability. Conclusions: The NMA supports topiramate, risperidone, quetiapine, paroxetine, venlafaxine, fluoxetine and sertraline as effective pharmacological choices for the treatment of PTSD. Quetiapine and topiramate have the shortcoming of relying on a few small studies, but the clinically meaningful change in symptoms is noteworthy and merits further investigation. Among the pharmacological treatments with evidence of efficacy compared to placebo, fluoxetine achieved a relatively high rank regarding acceptability. To the best of our knowledge, this is the largest contemporary NMA on the subject and the addition of new medications is an important extension of previous meta-analyses, enabling a larger number of drug comparisons.