A 79-year-old woman was admitted with new onset confusion. Her past medical history included heart failure and depression. On admission she was taking ramipril, metoprolol and frusemide. She had started mirtazapine 10 days previously.
The patient was euvolaemic. Her initial investigations revealed a low serum sodium of 113 mmol/L, low serum osmolality 243 mmol/kg (normal range 275-295 mmol/kg) and inappropriately high urine osmolality of 170 mmol/kg (normal range 50-1200 mmol/kg). Tests showed normal renal, thyroid and adrenal function. A diagnosis of inappropriate antidiuretic hormone secretion was suspected. Her chest X-ray and CT of the head did not show evidence of lesions potentially responsible for inappropriate secretion of antidiuretic hormone.
The patient's fluid intake was restricted, and frusemide and mirtazapine were ceased. Her confusion began to resolve after four days. Her serum sodium improved to 132 mmol/L by day 10. Frusemide was reintroduced, without a fall in serum sodium over the next few weeks. We therefore suspected that mirtazapine had caused her hyponatraemia.
Symptoms of severe hyponatraemia include confusion, weakness, lethargy, convulsions and coma. Hyponatraemia may be an under-reported adverse effect of mirtazapine which can result in hospitalisation. Clinicians should be aware of the possibility, particularly as early symptoms may mimic those of the patient's depression. We suggest patients with risk factors (see box) have a serum sodium measured before and 1-2 weeks after starting mirtazapine, or at any time if symptoms suggestive of hyponatraemia develop.
Risk factors for mirtazapine-induced hyponatraemia4
Pre-existing hyponatraemia or comorbidities associated with hyponatraemia
Concurrent drugs which can cause hyponatraemia
- Roxanas MG. Mirtazapine-induced hyponatraemia. Med J Aust 2003;179:453-4.
- Bavbek N, Kargili A, Akcay A, Kaya A. Recurrent hyponatremia associated with citalopram and mirtazapine. Am J Kidney Dis 2006;48:e61-2.
- Vacher CM, Fretier P, Creminon C, Calas A, Hardin-Pouzet H. Activation by serotonin and noradrenaline of vasopressin and oxytocin expression in the mouse paraventricular and supraoptic nuclei. J Neurosci 2002;22:1513-22.
- Madhusoodanan S, Bogunovic OJ, Moise D, Brenner R, Markowitz S, Sotelo J. Hyponatraemia associated with psychotropic medications. A review of the literature and spontaneous reports. Adverse Drug React Toxicol Rev 2002;21:17-29.