Analysis of the Frequency and Onset Time of Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Induced by Antidepressants or Antipsychotics

Abstract

Background Hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented. Objective To analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH. Methods We used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters. Results We identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age. Conclusion and Relevance Most ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.

A Conspectus of Euvolemic Hyponatremia, Its Various Etiologies, and Treatment Modalities: A Comprehensive Review of the Literature

“…Primary polydipsia is one of the most prominent factors in patients with psychosis, affecting nearly 7% of patients with schizophrenia [ 52 ]. Although the median onset time of total antidepressant-induced hyponatremia/SIADH was shorter than that for antipsychotic-induced hyponatremia [ 53 ], despite normal levels of ADH, some psychotropic drugs (sertraline, haloperidol), antiepileptics (carbamazepine, lamotrigine), and chemotherapeutics (cyclophosphamide) increase vasopressin V2 receptor (V2R) mRNA and aquaporin-2 (AQP2) protein expression of the inner medullary collecting duct cells, increasing water absorption even at normal or low ADH levels and leading to nephrogenic syndrome of inappropriate antidiuresis (NSIAD) [ 54 ]. Most idiosyncratic drug reactions resulting in hyponatremia involve more than one pathophysiology mentioned above.…”