Drug-Induced Hyponatremia: Insights into Pharmacological Mechanisms and Clinical Practice Management

Background: Hyponatremia (serum sodium concentration < 135 mmol/L) represents the most common electrolyte disturbance in clinical practice, particularly among high-risk populations such as older adults. Its severity ranges from moderately severe to life-threatening symptoms, contributing to increased mortality. Its etiology is widely heterogeneous and leads to different classifications according to volume status such as hypovolemic, euvolemic and hypervolemic hyponatremia. Drug-induced hyponatremia presents itself as one of the most prevalent but frequently overlooked causes, since many confounding factors like associated comorbidities and polypharmacy complicate the identification of specific medicines as the main offenders. Objectives: This narrative review was performed to provide a comprehensive analysis on drug-induced hyponatremia, focusing not only on the underlying pharmacological mechanisms, but also on management strategies in clinical practice. Methods: A narrative literature review was conducted using PubMed, Science Direct and Google Scholar. Results: This narrative review focused not only on the most common drug classes to induce hyponatremia through different mechanisms, including diuretics, antidepressants, anticonvulsants, and antipsychotics, but also on other pharmacological classes, that, although to a lesser extent, might also be associated with decreasing serum sodium levels (antineoplastic and immunomodulating agents, drugs acting on digestive and locomotor systems, anti-infective drugs, endocrine diseases drugs, among others). It also explores recommendations on the management of drug-induced hyponatremia and it emphasizes the role of healthcare providers in addressing this electrolyte disorder. Conclusions: As drug-induced hyponatremia poses significant challenges in clinical practice, understanding its mechanisms, coupled with effective management strategies, can enhance patient safety.