RATIONALE: Ketamine has emerged as a rapid-acting antidepressant. Lamotrigine is used as an off-label treatment for major depressive disorder. Some theorize, based on mechanism, that lamotrigine might interfere with ketamine's antidepressant effects.
OBJECTIVES: To report on clinical outcomes for patients with depression treated concomitantly with/without lamotrigine and ketamine/esketamine.
METHODS: Clinical outcomes based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology-Self Report (QIDS) were organized from patients with major depressive disorder treated with ketamine/esketamine at Yale Psychiatric Hospital from 2014 through November 2023. Patients were treated with intravenous ketamine (0.5 mg/kg over 40 min) or intranasal esketamine (56 or 84 mg) twice per week for two to four weeks.
RESULTS: Overall, 347 patients with depression were treated with ketamine/esketamine, 57 of which were concurrently taking lamotrigine during the treatment period. Most (207/347, 59.7%) patients were women, with an average age of 45.6 (standard deviation [SD] = 16.6). The average dose of lamotrigine was 210.1 (SD = 153.9). In the initial, unadjusted model, there was no group (lamotrigine v. no lamotrigine) by time interaction using the MADRS (F=1.19, p = 0.30) or QIDS (F=0.51, p = 0.60) as outcomes. Adjusting for concomitant medications (antidepressants, benzodiazepines), prior exposure to electroconvulsive therapy, sex, age, race, history of psychiatric hospitalization, additional psychiatric comorbidities, and whether patients started treatment as an outpatient or inpatient did not affect results. 2,345 2,338
CONCLUSIONS: We found no clinical evidence for an interaction between lamotrigine and treatment with ketamine/esketamine in a real-world sample of treatment-seeking patients with major depressive disorder.
