Lamotrigine, Contraceptives, and Psychiatry: A Narrative Review

Lamotrigine is widely used in neurology and psychiatry, particularly in epilepsy and mood disorders, due to its favorable efficacy and safety profile. However, clinically relevant pharmacokinetic interactions between lamotrigine and hormonal contraceptives have been increasingly recognized, raising concerns regarding therapeutic stability and reproductive safety in women of reproductive age. This narrative review examines the bidirectional interactions between lamotrigine and hormonal contraceptive methods, focusing on their pharmacokinetic mechanisms, clinical consequences, and implications for prescribing practice. Relevant studies were identified and narratively synthesized to investigate the bidirectional interactions between lamotrigine and hormonal contraceptive methods, focusing on their pharmacokinetic mechanisms, clinical consequences, and implications for prescribing practice. Available evidence consistently demonstrates that estrogen-containing contraceptives significantly reduce lamotrigine plasma concentrations through induction of hepatic glucuronidation, leading to substantial interindividual and intracycle variability. Cyclic contraceptive regimens further contribute to marked fluctuations in lamotrigine levels, with potential risks of subtherapeutic exposure during active hormone phases and toxicity during hormone-free intervals. In contrast, lamotrigine appears to exert minimal and clinically inconsistent effects on contraceptive efficacy, although hormonal fluctuations and breakthrough bleeding may occur. Progestin-only and non-hormonal contraceptive methods demonstrate more favorable pharmacokinetic profiles and are associated with greater therapeutic stability. Although most data derive from epilepsy populations, these interactions are also relevant in psychiatric practice, where lamotrigine is commonly prescribed for mood stabilization and where modest pharmacokinetic shifts may have a significant clinical impact. An understanding of these interactions is essential to avoid misinterpretation of symptom recurrence, prevent adverse effects, and support informed contraceptive counseling. An individualized, multidisciplinary approach is recommended to optimize both psychopharmacological treatment and reproductive care.