Efficacy and safety of antidepressant use in focal epilepsy with psychiatric comorbidities: a systematic review

Background: Patients with focal epilepsy frequently experience comorbid psychiatric disorders, complicating treatment and negatively impacting their quality of life. The use of antidepressants in this population raises concerns about the potential for increased seizure frequency. This study aims to systematically review the scientific literature on the efficacy and safety of antidepressants in patients with focal epilepsy and psychiatric comorbidities. Methods: A search was conducted across PubMed, MEDLINE, EMBASE, PsycINFO, Web of Science, and Scopus, focusing on clinical trials, observational studies, case reports, and case series involving patients over 18 years with focal epilepsy and psychiatric diagnoses treated with antidepressants. The ROBINS-I version 2 tool was used to assess bias in observational studies and clinical trials, while the Joanna Briggs Institute checklist evaluated the methodological quality of case reports and series, ensuring a thorough analysis of the studies’ internal validity. Results: 13 studies with 376 patients were included. Selective serotonin reuptake inhibitors (SSRIs: sertraline, escitalopram, fluoxetine), agomelatine, and vortioxetine were effective in reducing depressive and anxiety symptoms and improving sleep, without increasing the frequency of seizures. Venlafaxine was associated with hyponatremia and prolongation of the QT Interval (ventricular repolarization interval), and tricyclics showed seizure risks at high doses. Conclusions: SSRIs, agomelatine, and vortioxetine are safe and effective therapeutic options.