“Ms. L.,” a 30-year-old woman with no past medical history was being treated with ziprasidone 40 mg/day and paroxetine 30 mg/day for major depressive disorder. Paroxetine was discontinued, and sertraline 50 mg/day was initiated for persistent depressive symptoms. Sertraline was titrated to 125 mg/day in Week 4, with ziprasidone maintained at 40 mg/day. Two days later, the patient was brought to the emergency room for severe anxiety, jerking movements of upper extremities, and transient headaches. At presentation, her blood pressure was 134/92 mm Hg, heart rate, 122 beats per minute, and core temperature, 36.8°C. She appeared confused and diaphoretic. Neurological examination demonstrated mydriasis, with frequent, large-amplitude, sudden jerking movements. Extremities showed normal muscle tone, resting tremor with hyperreflexia, frequent myoclonus, and inducible ankle clonus. Laboratory studies were unremarkable. The creatine kinase level was normal (99 U/L). Urine toxicology was negative. Electrocardiography showed sinus tachycardia; cerebral computed tomography was normal. Urinalysis and chest radiographs were negative. The patient was given intravenous fluids and clonazepam 0.5 mg twice daily. Sertraline was discontinued, and ziprasidone was decreased to 20 mg/day. Most of Ms. L’s symptoms resolved within 48 hours, and, on Day 3, she was transferred to Psychiatry.