Drug-induced hyponatremia in clinical care

Over the last decades, advances in understanding of previously described associations have important implications for diagnosis and workup of hyponatremia. In addition, new drug groups potentially affecting sodium balance and water homeostasis have evolved. The aim of this review is to summarize current evidence on drug-induced hyponatremia in clinical care.

We searched PubMed using the string "Inappropriate ADH Syndrome/chemically induced"[Mesh] OR "Inappropriate ADH Syndrome/diagnosis"[Mesh]) OR ("Hyponatremia/chemically induced"[Mesh] OR "Hyponatremia/diagnosis"[Mesh]), January 1^st, 2008, to September 2^nd 2024. In total 2003 articles were found and reviewed. Relevant articles referenced herein were subsequently traced backwards and also reviewed.

Drugs associated with hyponatremia, including selective serotonin reuptake inhibitors, antipsychotics, antiepileptic drugs and proton pump inhibitors, typically cause hyponatremia shortly after initiation of treatment. For thiazide diuretics, the number one culprit in drug-induced hyponatremia, the risk for hyponatremia is highest the first weeks after initiation and then gradually decreases to a stable but still increased level after around 3 months. Several drugs that promote a negative water balance such as loop diuretics, lithium and of sodium-glucose cotransporter-2 inhibitors appear to decrease the risk for hyponatremia. Treatment with immune checkpoint inhibitors is associated with an increased risk of hypophysitis and adrenalitis resulting in hyponatremia due to secondary and primary cortisol deficiency.

For most drugs associated with hyponatremia, including thiazides, the cause-effect relationship is tightly linked to newly initiated treatment. Further research is warranted to characterize the association between hyponatremia and newly developed drugs such as sodium-glucose cotransporter-2 inhibitors and immune checkpoint inhibitors.