Antidepressant-induced hyponatremia/syndrome of inappropriate antidiuretic hormone (SIADH) can cause significant morbidity and mortality. Antidiuretic hormone release due to stimulation of central serotonin 5HT1C, 5HT2 and α-1 adrenergic receptors is thought to cause this adverse effect (Spigset, 1995). Evidence on which antidepressants are more likely to cause hyponatremia is inconsistent (Coupland, 2011; Leth-Moller, 2016). Owing to its uncommon use, there is limited and conflicting data on the risk of hyponatremia with Moclobemide, a reversible inhibitor of monoamine oxidase A (Mercier, 1997; Mazhar, 2019). There are few reports of hyponatremia induced by multiple antidepressant classes in the same patient.

To add to the literature on risk of hyponatremia with Moclobemide and other antidepressants.

We report a case of hyponatremia sequentially induced by multiple different antidepressant classes who was treated with Moclobemide with no recurrence of hyponatremia. We review existing literature on antidepressant-induced hyponatremia.

A 67-year-old man with a history of hypertension, dyslipidemia and gout was first diagnosed with major depressive disorder at age 50 after presenting with pervasive depressed mood, anhedonia, insomnia, poor concentration and feelings of worthlessness. Investigations found no medical causes of depression. His depression remitted on Venlafaxine 75mg/day with no hyponatremia induced. During a second depressive episode 4 years later, his serum sodium (Na) dropped from a normal baseline to 122mmol/L after Venlafaxine was restarted. He appeared euvolemic on physical examination. Investigations found no other causes of hyponatremia and were consistent with SIADH, which was attributed to Venlafaxine. His depression later remitted on Mirtazapine 30mg/day with no hyponatremia induced. During his third depressive episode at age 67, he developed hyponatremia (serum Na 123mmol/L) a week after restarting Mirtazapine. His clinical picture was consistent with SIADH. He later developed hyponatremia after initiating the following antidepressants sequentially: Fluvoxamine, Agomelatine, Nortriptyline, Bupropion. Hyponatremia resolved with fluid restriction and cessation of the implicated antidepressant each time before the next was initiated. He eventually tolerated Moclobemide 300mg/day with no recurrence of hyponatremia.

Agomelatine, Nortriptyline and Bupropion are reported to have a low risk of hyponatremia but were implicated in this case. Venlafaxine and Mirtazapine did not cause hyponatremia when first taken but were implicated when restarted after a period of cessation, underscoring the idiosyncratic nature of antidepressant-induced hyponatremia. Moclobemide can be considered for depressed patients with recurrent antidepressant-induced hyponatremia. Serum Na should be regularly monitored in patients taking antidepressants who are at high risk of hyponatremia.