Comparative Efficacy and Acceptability of Pharmacological, Psychotherapeutic, and Combination Treatments in Adults With Posttraumatic Stress Disorder: A Network Meta-analysis.

Importance: Posttraumatic stress disorder (PTSD) is a prevalent mental disorder, with a high risk of chronicity, comorbidity, and functional impairment; PTSD is complicated to treat, and the debate on the best treatment approach is ongoing. Objective: To examine comparative outcomes and acceptability of psychotherapeutic and pharmacological treatments and their combinations in adults with PTSD. Data Sources: Embase, MEDLINE, PsycINFO, Cochrane Controlled Trials Register, and PSYNDEX were searched for studies published from January 1, 1980, to February 28, 2018. Reference lists of included studies and of previously published guidelines and systematic reviews were also searched. Study Selection: Of 11 417 records identified, 12 published randomized clinical trials (RCTs) comprising 922 participants, contributing 23 direct comparisons between psychotherapeutic and pharmacological treatments or their combinations were included. Data Extraction and Synthesis: Standardized mean differences (SMDs) and odds ratios were aggregated using random-effects network and pairwise meta-analyses. Risk of bias and indirectness was rated for each study, and network confidence was rated using the Confidence in Network Meta-Analysis framework. Main Outcomes and Measures: The primary outcome was the comparative benefit between 2 treatment approaches to PTSD symptom improvement, and secondary outcome was the comparative acceptability of the treatment approaches, as indicated by patient dropout rates before treatment termination. Results: No treatment approach was found to be superior at the end of treatment (for all, 95% CI included 0). At the last follow-up, psychotherapeutic treatments showed greater benefit than pharmacological treatments in both network (SMD, -0.83; 95% CI, -1.59 to -0.07) and pairwise (SMD, -0.63; 95% CI, -1.18 to -0.09, 3 RCTs) meta-analyses. No difference was found between combined treatments and psychotherapeutic treatments at long-term follow-up, and combined treatments were associated with better outcomes than pharmacological treatments in the network meta-analysis (SMD, -0.96; 95% CI, -1.87 to -0.04), but not in the pairwise meta-analysis, which included 2 RCTs (SMD, -1.02; 95% CI, -2.77 to 0.72). No evidence was found for differential acceptability of the 3 treatment approaches. Conclusions and Relevance: These results suggest superiority of psychotherapeutic treatments over pharmacological treatments; network, but not pairwise, meta-analyses suggest superiority of combined treatments over pharmacological treatments in improving PTSD symptom severity in the long term. The scarcity of reported long-term findings hampers definite conclusions and demonstrates the need for robust evidence from large-scaled comparative trials providing long-term follow-up data.