SEROTONIN SYNDROME INDUCED BY VENLAFAXINE AND FLUOXETINE - A CASE-STUDY IN POLYPHARMACY AND POTENTIAL PHARMACODYNAMIC AND PHARMACOKINETIC MECHANISMS

OBJECTIVE: To document a case of serotonin syndrome associated with ve nlafaxine and fluoxetine that did not involve a monoamine oxidase inhi bitor, and to examine the multiple factors, including pharmacodynamic and pharmacokinetic interactions, that likely caused this adverse drug reaction (ADR). CASE SUMMARY: A 39-year-old white woman with depressi on and panic attacks was being treated with fluoxetine, trazodone, clo nazepam, and cimetidine. After fluoxetine and clonazepam were abruptly discontinued, venlafaxine and lorazepam were started. Within 24 hours , she developed diaphoresis, tremors, slurred speech, myoclonus, restl essness, impaired thinking, and diarrhea. This constellation meets Ste rnbach's criteria for serotonin syndrome. DISCUSSION: The possible con tributors to this ADR are discussed, including a single drug effect (e .g., an idiosyncratic reaction to venlafaxine), a pharmacokinetic inte raction, a pharmacodynamic interaction, a combined pharmacokinetic-pha rmacodynamic interaction, and the patient's panic disorder. CONCLUSION S: As more serotonergic drugs are developed and used for psychiatric d isorders, frequently in combination or close temporal proximity, clini cians must be aware of and consider the factors that may increase the risk of patients experiencing serotonin syndrome.