Evidence for the beneficial effect of ketamine in the treatment of patients with post-traumatic stress disorder: A systematic review and meta-analysis

Abstract

Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and "PTSD pharmacotherapeutic crisis". Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.

Keywords: Meta-analysis; ketamine; mental disorders; post-traumatic stress disorder (PTSD); stress disorders.

Figure 1.

PRISMA flow diagram.

Figure 2.

Judgments about each methodological quality of clinical studies included in the review. (Q1 – Was true randomization used for the assignment of participants to treatment groups?; Q2 – Was allocation to treatment groups concealed?; Q3 – Were treatment groups similar at the baseline?; Q4 – Were participants blind to treatment assignment?; Q5 – Were those delivering treatment blind to treatment assignment?; Q6 – Were outcomes assessors blind to treatment assignment?; Q7 – Were treatment groups treated identically other than the intervention of interest?; Q8 – Was follow-up complete and if not, were differences between groups in terms of their follow-up adequately described and analyzed?; Q9 – Were participants analyzed in the groups to which they were randomized?; Q10 – Were outcomes measured in the same way for treatment groups?; Q11 – Were outcomes measured in a reliable way?; Q12 – Was appropriate statistical analysis used?; Q3 – Was the trial design appropriate, and were any deviations from the standard RCT design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial?).

Figure 3.

Judgments about each methodological quality of clinical studies included in the review. (Q1 – Were the two groups similar and recruited from the same population?; Q2 – Were the exposures measured similarly to assign people to both exposed and unexposed groups?; Q3 – Was the exposure measured in a valid and reliable way?; Q4 – Were confounding factors identified?; Q5 – Were strategies to deal with confounding factors stated?; Q6 – Were the groups/participants free of the outcome at the start of the study (or at the moment of exposure)?; Q7 – Were the outcomes measured in a valid and reliable way?; Q8 – Was the follow-up time reported sufficient to be long enough for outcomes to occur?; Q9 – Was follow-up complete, and if not, were the reasons for loss to follow-up described and explored?; Q10 – Were strategies to address incomplete follow-up utilized?; Q11 – Was appropriate statistical analysis used?).

Figure 4.

Results of the meta-analysis of the effect of ketamine on symptoms associated with post-traumatic stress disorder assessed by the CAPS-5, PCL-5 and MADRS scales. (a) Baseline effect vs Best effect after ketamine treatment. (b) Baseline effect vs Best effect of ketamine in the first 24 hours after treatment and (c) Baseline effect vs Best effect of ketamine after 24 hours of treatment.