Agitation, sweating and hyperreflexia after adding tramadol to sertraline

A 40-year-old man with a history of major depressive disorder, well managed on sertraline 100 mg daily for the past 12 months, was admitted with a two-day history of agitation, excessive sweating, and twitching of his legs. Four days before admission, he had been started on tramadol 50 mg three times daily for acute low back pain. He also took paracetamol 500 mg as needed for pain. On the day of starting tramadol, he felt restless and anxious. Over the next 48 hours, he developed profuse sweating, tremor, and involuntary jerking of his limbs. He denied any fever or chills. On examination, he was agitated and alert. Heart rate was 118 beats per minute, blood pressure 150/90 mmHg, oral temperature 38.0°C, oxygen saturation 97% on air. Neurological examination revealed hyperreflexia in all limbs, sustained ankle clonus, and inducible wrist clonus. Plantar reflexes were flexor. No other focal neurological deficit was demonstrated. He had no rigidity or opisthotonos. Laboratory tests, including full blood count, urea and electrolytes, liver function tests, and inflammatory markers, were unremarkable. An electrocardiogram showed sinus tachycardia. A diagnosis of serotonin syndrome was made. Tramadol was stopped immediately. He was given intravenous fluids and lorazepam. Over the next 24 hours, his agitation and sweating resolved; clonus was no longer present by 36 hours. He remained well at discharge on day 3. A rechallenge was not undertaken. The differential diagnosis included an exacerbation of anxiety, but the presence of clonus and hyperreflexia made a serotonergic syndrome more likely. He had been stable on sertraline for a year, and the symptoms started shortly after tramadol was introduced.