The safety of the use of anti psychotics: analysis of spontaneous reports’ database

Introduction. Antipsychotics are widely used off-label for treating resistant forms of anxiety-depressive disorders, necessitating a thorough safety data collection for this class of medicinal products.

Objective. To assess the safety profile of antipsychotics recommended by the Russian Federation for treating patients with neurotic disorders.

Materials and methods. Spontaneous reports submitted to the "Pharmacovigilance" database of the Roszdravnadzor Automated Information System between 2019 and 2024 were analyzed for chlorprothixene, sulpiride, amisulpride, quetiapine, olanzapine, risperidone, and aripiprazole. For each international nonproprietary name, Reporting Odds Ratios (ROR) and Proportional Reporting Ratios (PRR) were calculated to assess statistically significant disproportionality.

Results. We obtained data from 1392 spontaneous reports, of which 1359 were primary reports. The number of spontaneous reports increased for most drugs, except for sulpiride, amisulpride, flupentixol, and ziprasidone. The total number of reports over the 5‑year observation period did not exceed 50 for flupentixol (n=21), lurasidone (n=35), ziprasidone (n=18), cariprazine (n=29), and amisulpride (n=14). The highest number of statistically significant associations between drug use and the development of adverse reactions across several system-organ classes was demonstrated for risperidone: disorders of the musculoskeletal and connective tissue (dystonia, tremor, hypertonia), disorders of the reproductive system and mammary glands (galactorrhea, amenorrhea), and laboratory/instrumental findings (hyperprolactinemia). Associations were confirmed with injuries, poisonings, procedural complications (poisoning, intentional poisoning, and neurotoxicity), and nervous system disorders (depressed level of consciousness, headache, and dizziness) for chlorprothixene. Associations between quetiapine and nervous system disorders (tremor, stupor, somnolence), injuries, poisonings, and procedural complications (neurotoxicity, poisoning, and overdose) Associations were found between aripiprazole, flupentixol, and lurasidone with musculoskeletal and connective tissue disorders (dystonia). Cariprazine was associated with psychiatric disorders (agitation, anxiety, and 1 case of completed suicide).

Conclusions. The overall reporting level remains extremely low. Considering the international experience in collecting safety data on antipsychotics, a significant number of cases may be underreported, including suicides and self-harm, overdoses, rhabdomyolysis, neuroleptic malignant syndrome, closed-angle glaucoma associated with olanzapine use, and acute pancreatitis associated with quetiapine use.

1. Højlund M, Andersen JH, Andersen K, et al. Use of antipsychotics in Denmark 1997-2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses. Epidemiol Psychiatr Sci. 2021 Apr 6;30:e28. doi: 10.1017/S2045796021000159.

2. Su CC, Chia-Cheng Lai E, Kao Yang YH, et al. Incidence, prevalence and prescription patterns of antipsychotic medications use in Asia and US: A cross-nation comparison with common data model. J Psychiatr Res. 2020 Dec;131:77-84. doi: 10.1016/j.jpsychires.2020.08.025.

3. Radha Krishnan RP, Harrison C, Buckley N, Raubenheimer JE. On- and off-label utilisation of antipsychotics in Australia (2000-2021): Retrospective analysis of two medication datasets. Aust N Z J Psychiatry. 2024 Apr;58(4):320-333. doi: 10.1177/00048674231210209.

4. Pharmacovigilance / under the general direction ed. Kolbin A. S., Zyryanov S. K., Belousov D. Yu. 2nd ed. (corrected and expanded). Moscow: OKI Publishing House: Buki Vedi, 2025. 276 p. : ill. ISBN 978-5-4465-4266-6 (In Russ.).

5. Simon LV, Hashmi MF, Callahan AL. Neuroleptic Malignant Syndrome. 2023 Apr 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.

6. Tan CM, Kumachev A. Neuroleptic malignant syndrome. CMAJ. 2023 Nov 6;195(43):E1481. doi: 10.1503/cmaj.221763.

7. Zhang Y, Deng W, Wang M, et al. A real-world pharmacovigilance study of neuroleptic malignant syndrome based on FDA adverse event reporting system. Front Pharmacol. 2024 Dec 11;15:1438661. doi: 10.3389/fphar.2024.1438661.

8. Song M, Li D, Peng J, Wang N, Zhang M, Ren XL. A disproportionality analysis of antipsychotic-induced hyperprolactinemia based on FDA adverse event reporting system. Int J Clin Pharmacol Ther. 2024 Dec;62(12):543-552. doi: 10.5414/CP204518.

9. Frey C. Quetiapine is associated with pancreatitis: A real-world pharmacovigilance study. J Affect Disord. 2025 Apr 1;374:72-74. doi: 10.1016/j.jad.2025.01.042.

10. Xie WL, Xiang DC, Li YY, et al. An exploratory study evaluating the 20 medications most commonly associated with suicidal ideation and self-injurious behavior in the FAERS database. BMC Pharmacol Toxicol. 2025 Jan 30;26(1):24. doi: 10.1186/s40360-025-00858-7.

11. Yin Y, Jiang J, Jin Y. Evaluation of atypical antipsychotics associated rhabdomyolysis using the FDA adverse event reporting system database. Sci Rep. 2025 Mar 26;15(1):10499. doi: 10.1038/s41598-025-95700-9.

12. Ni J, Tang X, Chen L. Medication overdose data analysis: a review of medication error reports in the FDA adverse event reporting system (FAERS). BMC Pharmacol Toxicol. 2023 Aug 4;24(1):41. doi: 10.1186/s40360-023-00681-y.

13. Qiu W, Wang D, Deng J, Jin L. An analysis of the association between atypical antipsychotic drugs and glaucoma risk: a disproportionality assessment based on the FAERS database. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 18. doi: 10.1007/s00210-025-04610-0.