To the Editor: Serotonin toxicity is an under-recognised, potentially fatal syndrome that is becoming more common as the use of serotonergic drugs increases.1 We report a case of serotonin toxicity following the concomitant use of the antidepressant citalopram and methylene blue.

A 44-year-old woman underwent elective partial parathyroidectomy for primary hyperparathyroidism. Three hours after surgery, the patient became agitated and restless while staring vaguely into space, making incomprehensible sounds (Glasgow Coma Scale: 11/15; motor response, 5; verbal response, 2; eye opening, 4). Her blood pressure (120/66 mmHg), pulse (100 beats/minute [sinus rhythm]), oxygen saturation (92% while breathing room air), and temperature (37.5°C) were not clinically significant.

Neurological examination revealed bilateral pupillary dilatation with sluggish response to light, myoclonic movements of the lower limbs, brisk reflexes throughout and downgoing plantar responses. Clonus was absent and there was no focal neurological deficit. Blood tests showed a mild inflammatory response (white cell count, 12.7 × 109/L [reference range (RR), 4.0–11.0 × 109/L]; C-reactive protein, 23 mg/L [RR, < 10 mg/L]), normal serum levels of calcium (2.50 mmol/L [RR, 2.12–2.65 mmol/L]), and mildly elevated phosphate (1.5 mmol/L [RR, 0.8–1.4 mmol/L]). A computed tomography scan of the head showed no abnormalities.

The patient’s medical history included ischaemic heart disease, hypertension, obesity and depression. Regular long-term medications included aspirin (75 mg daily), simvastatin (40 mg each night), atenolol (50 mg daily), isosorbide mononitrate (20 mg daily), bendroflumethiazide (a thiazide diuretic not available in Australia; 2.5 mg daily), felodipine (5 mg daily) and citalopram (20 mg daily). On the day of the operation, she received propofol, remifentanil, rocuronium, dexamethasone, morphine analgesia and a preoperative methylene blue infusion (560 mg in 500 mL of saline over 2 hours; used to stain the parathyroid glands). She had previously undergone general anaesthesia without complication.

Serotonin toxicity was diagnosed, precipitated by the combination of methylene blue and citalopram. She was transferred to the intensive care unit, where she was sedated for 12 hours with propofol and alfentanil. Citalopram was withheld, and she received supportive treatment only. She was discharged to the ward 24 hours later and then home (3 days after discharge from the intensive care unit), with no long-term adverse effects. Three months after discharge, she continued to take citalopram, and serum calcium levels were in the normal range.

Serotonin toxicity can be caused by a single drug or a combination of drugs with serotonergic activity. Methylene blue attenuates the metabolism of serotonin through inhibition of monoamine oxidase A.2 When used in combination with a selective serotonin reuptake inhibitor, such as citalopram, toxic accumulation of serotonin may result.3 Features include mental state changes, autonomic hyperactivity, and neuromuscular abnormalities. In mild cases, treatment is supportive, with withdrawal of serotonergic drugs and control of agitation. Moderate to severe cases require control of hyperthermia and autonomic instability, and administration of 5-HT2A (5-hydroxytryptamine2A) antagonists.1