Safety of Anxiolytics: Analyzing the Russian Database of Spontaneous Reports

INTRODUCTION. Expanding prescription of anxiolytics due to high global incidence of anxiety disorders necessitates a safety assessment of these drugs in clinical practice.

AIM. This study aimed to assess the risks of adverse drug reactions (ADR) to the anxiolytics prescribed for neurotic disorders in the Russian Federation and to identify drugs with the most favorable safety profile.

MATERIALS AND METHODS. Spontaneous reports were submitted to Roszdravnadzor Automated Information System database over 2019–2024 (n=1,024) for drugs with the following international non-proprietary names: diazepam, tofisopam, bromdihydrochlorphenylbenzodiazepine, alprazolam, lorazepam, etifoxine, buspirone, and fabomotizole. The reporting odds ratio (ROR) and the proportionality ratio of reporting (PRR) were calculated for each international non-proprietary name regarding the most frequently reported ADR system organ classes (SOC).

RESULTS. Fatal ADRs were significantly associated with diazepam administration (ROR 10.98, [4.81, 25.05], p<0.001; PRR 48.56, p<0.001). A statistically significant ADR-drug association was established for: 1) diazepam and ADRs related to SOC Immune system disorders; General disorders and administration site conditions; Respiratory, thoracic and mediastinal disorders; and Vascular disorders; 2) bromdihydrochlorphenylbenzodiazepine and ADRs related to SOC Nervous system disorders and Psychiatric disorders; 3) tofisopam and ADRs related to SOC Gastrointestinal disorders. The risk of poisoning, overdoses, as well as suicide or intentional poisoning for benzodiazepine anxiolytics was comparable to non-benzodiazepine drugs (OR for poisoning/overdose 1.41 [0.46, 4.29], p=0.27; OR for suicide/intentional poisoning 1.75, [0.79, 3.9], p=0.08).

CONCLUSIONS. Hydroxyzine has been deemed the safest non-benzodiazepine anxiolytic, with diazepam being the least safe. Due to the low number of reports, further monitoring of ADR risks is warranted.

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