Background: Most international guidelines suggest that benzodiazepines (BDZs) may be inefficient or iatrogenic in the aftermath of a potentially traumatic event (PTE). The goal of this study was to assess the strength of the evidence on whether the use of BDZs in the aftermath of a PTE negatively affects the incidence and severity of post-traumatic stress disorder (PTSD). Methods: We systematically scrutinized the ISI Web of Knowledge, MEDLINE, SCOPUS, and PTSDpubs electronic databases in addition to citation searching. We included original studies providing data about the development of PTSD in adults after BDZ administration in the aftermath of a PTE. We screened 387 abstracts and selected eight studies for the qualitative synthesis and seven for the meta-analysis. We performed two separate meta-analyses, one for randomized clinical trials (RCTs) and the other for cohort studies. Heterogeneity between studies was evaluated with Higgins I² statistic and tested using the χ². This study was registered at PROSPERO (number 127170). Results: The meta-analysis of the cohort studies showed an increased risk of PTSD in patients who received BDZs compared to those who did not (risk ratio (RR) = 1.53; 95% confidence interval (CI): 1.05–2.23) with a modest heterogeneity among studies ( I2 = 41.8, p = 0.143). Regarding the RCTs, the combined measure revealed a tendency toward an increased severity of the PTSD symptoms (standardized mean difference (SMD): 0.24; 95% CI: 0.32–0.79). Conclusion: The studies reviewed showed a possible harmful effect of BDZs when used immediately after a PTE. However, these conclusions were based on a small number of studies of poor to moderate methodological quality.

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