Efficacy and safety of etifoxine versus alprazolam in the management of adjustment disorder with anxiety (ADWA)

Background Well-conducted treatment trials and data on predictors of treatment response are both lacking for ADWA, despite the high prevalence of the condition. While benzodiazepines are frequently prescribed for anxiety disorders, etifoxine is also an effective agent not associated with dependence. A randomized controlled trial of etifoxine versus alprazolam for ADWA was undertaken, aiming at comparing efficacy and safety of the two treatments, and investigating predictors of the clinical response. Methods Two hundred and two adult outpatients with ADWA were enrolled at primary care settings sites in South Africa. Patients were followed for 4 weeks of treatment, and for an additional week after treatment discontinuation. The primary outcome measure was the Hamilton Anxiety Rating Scale (HAM-A) and was assessed by using a non-inferiority analysis. Secondary outcomes included the Sheehan Disability Scale (SDS) and the Clinical Global Impressions-Change Scale (CGI-C). Predictors of response were investigated with a multivariate logistic regression. Results Both etifoxine and alprazolam dramatically decreased the HAM-A score at 4 weeks. The difference between treatment groups in HAM-A was of 1.78 [90% CI; 0.23, 3.33] in favor of alprazolam. The two treatments were equally efficacious in patients with more severe anxiety symptoms at baseline. Between week 4 and week 5, after treatment discontinuation, HAM-A scores continued to improve in the etifoxine group, but increased in the alprazolam group ( P = 0.019); no difference was found between the two groups regarding the secondary outcomes. No significant predictors of treatment response were found. Patients treated with alprazolam experienced more treatment-related adverse events, mostly of central nervous origin, and especially after medication discontinuation. Conclusion This trial confirms the efficacy and safety of etifoxine in the management of ADWA.