Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis - PubMed (original) (raw)

Meta-Analysis

Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis

Thaís Pereira Mendes et al. Prog Neuropsychopharmacol Biol Psychiatry. 2025.

Abstract

Posttraumatic stress disorder (PTSD) is a debilitating condition affecting 5.7 % of the global population in their lifetime. There is a strong association between trauma-related nightmares and insomnia with higher rates of physical illness, mental distress, and suicide among PTSD patients. Prazosin, an α1-adrenergic antagonist, has shown mixed results in treating these sleep disturbances. This study aims to evaluate the effect of prazosin compared to placebo on insomnia, nightmares, and global PTSD symptoms, and to examine variables that might influence this effect. We conducted a meta-analysis and a novel meta-regression analysis of randomized clinical trials (RCTs) comparing prazosin to placebo in samples of patients with PTSD. Data sources were MEDLINE, EMBASE, Scopus, ISI Web of Science, and PTSD Pubs. Examined variables were age, gender, military/civilian status, prazosin dose, treatment duration, baseline symptom severity, use of antidepressants, use of benzodiazepines (BDZ), prevalence of depression, and alcohol use disorder. Ten RCTs with 648 patients were included. Analysis revealed prazosin significantly improved insomnia (SMD = -0.654, p = 0.043) and nightmares (SMD = -0.641, p = 0.025), but not overall PTSD symptoms (SMD = -0.428, p = 0.077). Unexpectedly, higher BDZ use was associated with greater improvement in insomnia (β = -0.046; p = 0.01) and PTSD severity (β = -0.037; p = 0.004). These findings suggest that prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy, suggesting that the addition of prazosin might allow for a reduction of BDZ doses in these patients. Further research should empirically test the efficacy of prazosin alone versus prazosin combined with BDZ to confirm these findings.

Keywords: Benzodiazepines; Insomnia; Meta-analysis; Nightmares; Posttraumatic stress disorder; Prazosin.

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Conflict of interest statement

Declaration of competing interest The authors report no conflicts of interest.

Figures

Fig. 1..

PRISMA flow diagram of the study selection.

Fig. 2..

Risk of bias of the included studies.

Fig. 3..

Forest plot for the difference of endpoint means of insomnia symptoms (standardized mean difference-SMD) and respective 95% confidence intervals between prazosin and placebo groups. Mahr et al. (2023) used only 4 PSQI items, each one with a different SD, therefore we decided not to include it in our analysis. Simpson et al. (2015) did not include insomnia measures, therefore it also couldn’t be included.

Fig. 4..

Association between the effect size of prazosin on insomnia and percentage of users of benzodiazepines. The size of the circles increases as the sample size increases (precision of the estimates).

Fig. 5..

Forest plot for the difference of endpoint means of nightmare severity (standardized mean difference-SMD) and respective 95% confidence intervals between prazosin and placebo groups.

Fig. 6..

Forest plot for the difference of endpoint means of PTSD severity (standardized mean difference-SMD) and respective 95% confidence intervals between prazosin and placebo groups.

Fig. 7..

Association between the effect size of prazosin on PTSD severity and percentage of users of benzodiazepines. The size of the circles increases as the sample size increases (precision of the estimates).

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Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis - PubMed (original) (raw)