Safety of Antidepressants: Analysis of the Russian Database of Spontaneous Reports

INTRODUCTION . Extensive use of antidepressants in a wide range of indications, including off-label use, as well as application in vulnerable groups of patients, shows the need to summarise the available safety data of these medicinal products. AIM. This study aimed to evaluate safety profile of antidepressants prescribed for neurotic disorders in the Russian Federation. MATERIALS AND METHODS . The study analysed spontaneous reports registered by Pharmacovigilance database of Roszdravnadzor Automated Information System in 2019–2024 for medicines with international nonproprietary names: fluvoxamine, citalopram/escitalopram, paroxetine, fluoxetine, sertraline, venlafaxine, duloxetine, vortioxetine, amitriptyline, clomipramine, mirtazapine, and imipramine. Reporting odds ratio and proportional reporting ratio was calculated for each international non-proprietary name with respect to statistically significant disproportionality. RESULTS. Amitriptyline resulted in the maximum number of reports (n=470), the minimum registered for imipramine (n=2). For most of the medicines, the total spontaneous reports over the five years of follow-up did not exceed 100. Statistically significant associations between the treatment and adverse drug reactions (ADRs) were demonstrated for the atypical antidepressant vortioxetine, for example, mental, endocrine, cardiac, and reproductive system disorders. Association with laboratory and instrumental disorders was confirmed for agomelatine. Among selective serotonin reuptake inhibitors, the following ADR relationships were statistically significant: fluoxetine — gastrointestinal disorders; fluvoxamine — eye disorders; paroxetine — ADRs in the systemic organ class Injury, Poisoning and Procedural Complications; sertraline — endocrine disorders. Use of selective sero­tonin reuptake inhibitors venlafaxine and duloxetine was significantly associated with immune system disorders. Treatment with tricyclic antidepressant amitriptyline is associated with nervous system disorders. Moreover, there was a high reporting rate from singular health facilities and pharmaceutical companies regarding certain products (atypical antidepressants, selective serotonin reuptake inhibitors, and norepinephrine reuptake inhibitors) and ADRs (such as oculogyric spasm for selective serotonin reuptake inhibitors). CONCLUSIONS. In 2019–2024, the number of spontaneous reports on ADRs caused by antidepressants increased every year; however, overall reporting remained low. Low number of spontaneous reports that do not align with actual consumption data, as well as discrepancy defined between incoming spontaneous reports on certain medicinal products and ADRs make it impossible to assess safety profile of the products considered. To determine safety profile of the medicinal products, further studies based on real clinical practice are recommended.