Chronic tramadol abuse as a cause of serotonin syndrome

Serotonin syndrome is characterized by autonomic hyperactivity, altered mental status, and neuromuscular abnormalities, ranging from mild to life-threatening manifestations. Tramadol has been associated with serotonin syndrome, predominantly in combination with other serotonergic agents or following acute overdose. Reports describing serotonin syndrome caused by chronic high-dose tramadol use as a single serotonergic agent are scarce. A case of serotonin syndrome in a young adult with chronic high-dose tramadol dependence in the absence of co-ingested serotonergic drugs is presented. A 22-year-old man with tramadol dependence (800 mg daily) presented to the emergency department with anxiety and agitation. Physical examination revealed diaphoresis, mydriasis, tachycardia (130 beats/min), hypertension (140/100 mmHg), hyperreflexia, and inducible ankle clonus. Laboratory investigations, head computed tomography, and urine toxicology screening were unremarkable. Based on the presence of inducible clonus and hyperreflexia in the setting of serotonergic exposure, the Hunter Serotonin Toxicity Criteria were fulfilled. Tramadol was discontinued and replaced with methadone. The patient recovered completely within 48 h. This case illustrates that chronic high-dose tramadol use alone may precipitate serotonin syndrome. Clinicians should remain alert to this potentially life-threatening complication, even in the absence of concomitant serotonergic medication.