Serotonin Syndrome Without Overdose: Polypharmacy-Induced Toxicity in a Medically Stable Young Adult

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin activity in the central and peripheral nervous systems that can lead to symptoms such as altered mental status, autonomic instability (e.g., hyperthermia and hypertensive tachycardia), and neuromuscular abnormalities (e.g., clonus and tremor). We present the case of a 29-year-old male healthcare worker with a history of major depressive disorder (MDD), temporal lobe epilepsy, and suspected obsessive-compulsive disorder (OCD) who presented with sudden-onset agitation, confusion, and abnormal limb movements after his third consecutive 12-hour overnight shift. He had been on stable outpatient doses of escitalopram 20 mg and bupropion XL 150 mg daily for over six months, with naltrexone 50 mg added three months earlier for off-label psychiatric use. In the emergency department, he was treated for presumed seizure or psychosis with multiple sedatives and antipsychotics and subsequently intubated. EEG showed no epileptiform activity, and lumbar puncture was unremarkable. Neurologic findings, including hyperreflexia, clonus, and rigidity, along with rapid clinical improvement following cyproheptadine and benzodiazepines, supported a diagnosis of serotonin syndrome. The patient denied overdose or substance use, and toxicology review concluded that polypharmacy with serotonergic and modulating agents was the likely trigger. We present a young adult who developed serotonin syndrome without overdose, likely due to the cumulative serotonergic effect of multiple prescribed medications at therapeutic doses. This case emphasizes the importance of clinical vigilance in patients with neuropsychiatric comorbidities on centrally acting agents, even in the absence of recent medication changes. It illustrates that even therapeutic combinations of serotonergic and modulating agents can precipitate life-threatening toxicity.