Abstract
Objective: This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical decision-making basis for clinicians. Method: A comprehensive search was conducted using Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Scopus, ScienceDirect, and Web of Science for randomized controlled trails (RCTs), which reported pharmaceutical management and placobo for adults with combat-related PTSD, that were published until April 21, 2021. The effectiveness, acceptability, and adverse events (AEs), were designed as interested outcomes. The change in total symptoms of combat-related PTSD according to the clinician rating scale was defined as primary outcome, and the others were defined as secondary outcomes. Results: Twenty-two RCTs with 1,221 patients were involved. Compared with placebo, overall active comparators had statistical differences for all outcomes, including the change in total symptoms of combat-related PTSD [SMD = −0.36, 95%CI (−0.62,−0.09)], depression [SMD = −0.28, 95%CI (−0.45,−0.10)], anxiety [SMD = −0.44, 95%CI (−0.64,−0.23)], re-experience [SMD = −0.33, 95%CI (−0.52,−0.13)], avoidance [SMD = −0.24, 95%CI (−0.43,−0.05)], and hyper-arousal [SMD = −0.26, 95%CI (−0.48,−0.03)]. Compared with the placebo, in terms of acceptability, overall active comparators did not significantly decrease all-cause discontinuance rates [RR = 0.97, 95%CI (0.78,1.20)], and the significance decreased due to AEs [RR = 2.42, 95%CI (1.41,4.13)]. Nevertheless, overall there was no statistically significant difference for overall AEs, including somnolence, sedation, dizziness, paresthesia, anxiety, blurred vision, generalized anxiety disorder, and sleep disturbance. All funnel plots were symmetrical and no publication bias was found. Conclusion: Active drugs, especially amitriptyline, imipramine, and quetiapine, had a positive effect on the improvement of combat-related PTSD symptoms. Despite there being no significant increase in the AEs of the active drugs, the fact that the discontinuation rates of these drugs, including risperidone, imipramine, and topiramate, were increased deserves attention. Furthermore, as active drugs were effective across ethnic groups and battlefields, active drug regimens were revealed to be more appropriate for treating people with symptoms of extreme severe PTSD (≥80) or PTSD that is at least 8 weeks old. In addition, current evidence was from adults under 60 years of age and male combat-related PTSD. Whether this evidence can be extended to other populations of combat-related PTSD needs to be confirmed by subsequent high-quality, large-sample studies.
Highlights
Post-traumatic stress disorder (PTSD) is a kind of stress disorder with severe clinical symptoms, poor prognosis, and possible brain damage in traumatic and stress-related disorders (Mithoefer et al, 2018)
3.3.1.4 Symptoms of Re-Experiencing In terms of changes in the symptoms of anxiety, eight drugs in 9 randomized controlled trials (RCTs) were compared with placebo in this study
It is worth noting that cardiotoxicity was the main adverse effect of excessive use of TCAs, and sodium bicarbonate was used to treat poisoning. This was different from other studies (Puetz et al, 2015) that looked at medications for anxiety and depression, in which treatment with selective serotonin reuptake inhibitors (SSRIs) and TCAs have been found to reduce PTSD, anxiety, and depression symptoms in veterans
Summary
Post-traumatic stress disorder (PTSD) is a kind of stress disorder with severe clinical symptoms, poor prognosis, and possible brain damage in traumatic and stress-related disorders (Mithoefer et al, 2018). The lifetime prevalence of PTSD in adults is approximately 8% (Kessler et al, 2012; Nichter et al, 2021), between 10 and 20% of trauma survivors in some cases develop chronic PTSD This brings considerable distress to society, families, and individuals, and causes huge economic and social burdens, and even increases the risk of suicide (Kessler et al, 1995; Kessler, 2000; Frayne et al, 2004; Krysinska and Lester, 2010; Wittchen et al, 2011). Based on the fact that treating PTSD with conventional drugs can involve major challenges, including excessive adverse effects, limited efficacy, and lower patient compliance, this study comprehensively evaluates the efficacy, acceptability, and safety of active drugs for PTSD, and explores the influence of relevant confounding factors on PTSD to ensure the reliability and extrapolation of evidence, and provide a reference for clinicians when making treatment decisions
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