Combination of Methylphenidate, Venlafaxine, and Escitalopram Resulting in Serotonin Syndrome

Abstract

Objective: To report a case of possible serotonin syndrome resulting from the addition of methylphenidate and/or escitalopram to venlafaxine. Case Summary: A 23-year-old woman being treated for bipolar depression experienced suspected serotonin syndrome. During the course of hospitalization, several medication changes were implemented. Despite these treatment interventions, depressive symptoms persisted during combination therapy with venlafaxine, lamotrigine, and gabapentin. Clinical problems developed when escitalopram and methylphenidate were later added to the regimen within a 2 day period. Several hours after receiving the second dose of methylphenidate, the patient developed a fever, exhibited hallucinations, and began hyperventilating. She was managed with supportive measures with some response, but continued to be lethargic and dizzy. Physical examination revealed increased rigidity of the upper extremities and labile blood pressure. Serotonin syndrome was suspected and all medications were withheld; the patient was then transferred to the intensive care unit. Discussion: Prompt and accurate diagnosis of serotonin syndrome is difficult but requires the presence of serotonergic agents in addition to core symptoms that have been identified through years of clinical antidepressant use. Additionally, serotonin syndrome is often complicated by other drug-related disorders with overlapping symptoms. Separately and together, escitalopram, venlafaxine, and methylphenidate have the ability to increase serotonin levels. Utilizing the Naranjo probability scale, we determined the likelihood of both methylphenidate and escitalopram contributing to serotonin syndrome as possible. Review of the established criteria for diagnosing serotonin syndrome, the clinical presentation of the patient, and the time frame of symptom development in correlation with drug therapy changes suggests that this is a case of serotonin syndrome. Conclusions: We believe that this was most likely a case of serotonin syndrome, precipitated by the addition of methylphenidate and/or escitalopram to venlafaxine.