Clonidine for post-traumatic stress disorder: a systematic review of the current evidence

Abstract

Background: Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep.Objective: In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD.Method: PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented.Results: Ten reports, accounting for N = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications.Conclusions: Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.

Keywords: Post-traumatic stress disorder; Trastorno de estrés postraumático; agente antiadrenérgico; anti-adrenergic agent; clonidina; clonidine; nightmares; pesadillas; sleep; sueño.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The figure shows the flowchart of the review phases, reporting the number of records identified, screened, and included. The main reason for exclusion among the full texts assessed was the absence of outcome data of interest for this review.

Figure 2.

Forest plot of the effect of clonidine on post-traumatic stress disorder (PTSD)-related nightmares. The figure shows the effect size of the two studies included in the meta-analysis and their pooled estimate, with relative 95% confidence intervals (95% CI) (Detweiler et al., ; Wendell & Maxwell, 2015). The confidence intervals for all estimates cross the line of no effect, indicating no statistical significance. The two studies have similar weights in the analysis. The meta-analysis includes 69 participants treated with clonidine and 395 controls; MH = Mantel Haenszel.