Eficácia, aceitabilidade e tolerabilidade do tratamento farmacológico do transtorno de estresse pós-traumático e dos antidepressivos na qualidade do sono de adultos com transtorno de estresse pós-traumático: revisões sistemáticas e metanálises em rede

Abstract

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.

Efficacy, Acceptability, and Tolerability of Antidepressants for Sleep Disturbance in Post-Traumatic Stress Disorder: a Systematic Review and Network Meta-Analysis.

Sleep complaints are a common occurrence in post-traumatic stress disorder (PTSD) and may remain after evidence-based treatment for PTSD has been implemented. If left untreated, sleep disturbance can perpetuate or aggravate the disorder. A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted comparing efficacy, acceptability, and tolerability among antidepressants for sleep disturbance in adults with PTSD, using Cochane‟s RoB2.0 and GRADE approach for NMA. The Cochrane Library, LILACS, PsycINFO, PTSDpubs, and PubMed Central databases were searched from inception to November 29, 2020, leading to the retrieval of 3,733 reports. After the selection process, seven RCTs were included in the review (N=600). We found low certainty of evidence (LCE) that sertraline may improve sleep quality (measured by PSQI) in patients with PTSD (MD –0.48, 95% CrI –0.63 to –0.32). Sertraline was as well accepted (RR 1.12, 95% CrI –0.83 to 1.52, very low certainty [VLCE]) and as well tolerated as placebo (RR 0.58, 95% CrI 0.28 to 1.14, LCE). Mirtazapine (MD –3.35, 95% CrI –9.06 to 2.39, LCE), paroxetine (MD –3.13, 95% CrI –7.47 to 1.26, VLCE), nefazodone (MD –0.25, 95% CrI –5.95 to 5.38, VLCE), and bupropion (MD –2.28, 95% CrI –4.75 to 0.21, VLCE) were similar to placebo for improving sleep quality. These antidepressants resulted in little or no benefit for sleep disturbances in PTSD. Although the NMA suggested that sertraline may improve sleep in PTSD compared to placebo, due to the low certainty, these estimates are not robust enough to guide clinical decisions.