Possible Interaction of Tramadol and Antidepressants

Clinicians wishing to follow the recommendations of Toby D. Goldsmith, M.D., et al. (1) in using tramadol hydrochloride to achieve rapid remission of obsessive-compulsive disorder (OCD) should be advised that drug-drug interactions may result if concomitant antidepressant treatment is used. In the case presented in the letter by Dr. Goldsmith and colleagues, a patient with OCD was receiving fluoxetine, 20–40 mg/day, in addition to tramadol in the course of her treatment. The authors mention the possibility of a serotonin syndrome developing but do not discuss the risk for seizure, which may result from P₄₅₀ inhibition induced by the selective serotonin reuptake inhibitor (SSRI), as well as competitive binding to the substrate. This is a documented warning in the Physicians’ Desk Reference, and patients receiving both types of medication should be fully informed of this possibility to minimize medical-legal risk.