Review: Drug Interactions Between Depression and Epilepsy Therapy

Abstract

Background: Managing comorbid depression and epilepsy is challenging due to complex drug-drug interactions (DDIs). Objective: This systematic review evaluates clinically significant pharmacokinetic and pharmacodynamic interactions between antidepressants and antiepileptic drugs (AEDs). Methods: A systematic search was conducted across PubMed, ScienceDirect, and Google Scholar (2010–2025) following PRISMA guidelines. Results: Of 377 identified records, 24 studies met the inclusion criteria. Pharmacokinetic interactions (n=18; 75%) primarily involve the CYP450 enzyme system, notably CYP2D6 inhibition by fluoxetine and induction by carbamazepine. Significant pharmacodynamic risks include serotonin syndrome (n=3) and lowered seizure thresholds. Conclusion: While modern therapies offer better safety profiles, specific combinations like valproate-lamotrigine or SSRI-tramadol require rigorous monitoring. Clinical Implications: Pharmacists must prioritize screening for enzyme-inducing AEDs to prevent therapeutic failure or toxicity in neuropsychiatric care.