Review: Drug Interactions Between Depression and Epilepsy Therapy

Erwin Samsul (Universitas Mulawarman)
Sandrina Nur Yulianda (Universitas Mulawarman)
Rahmawati Eka Sari (Universitas Mulawarman)
Dina Nurfauziah Rahmi (Universitas Mulawarman)
Rahma Nur Afifah (Universitas Mulawarman)
Risma Nur Ramadhani (Universitas Mulawarman)
Annisa Azhalia Syakina (Universitas Mulawarman)
Selvina Nirmaya Saputri (Universitas Mulawarman)
Listra Febrina Taruk (Universitas Mulawarman)

Journal of Pharmaceuticals and Natural Sciences
Vol. 3 No. 2 (2026): J Pharm Nat Sci

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.