SynthesisThe international journal of neuropsychopharmacology2021
Hyponatremia Following Antipsychotic Treatment: In Silico Pharmacodynamics Analysis of Spontaneous Reports From the US Food and Drug Administration Adverse Event Reporting System Database and an Updated Systematic Review.
Synthesis in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Comparative Risk of Hyponatremia Among Patients Treated With Second-Generation Antipsychotics.JAMA network open · 2026Article
- Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance-pharmacodynamic analysis using VigiBase.Therapeutic advances in psychopharmacology · 2026Article
- Drug-Induced Hyponatremia: Insights into Pharmacological Mechanisms and Clinical Practice Management.Journal of clinical medicine · 2025Review
- Electrolyte Disturbances Related to Sodium and Potassium and Electroconvulsive Therapy: A Systematic Review.Journal of clinical medicine · 2023Review
- On the potential of drug repurposing in dysphagia treatment: New insights from a real-world pharmacovigilance study and a systematic review.Frontiers in pharmacology · 2023Article
- Potential Use of Pharmacogenetics to Reduce Drug-Induced Syndrome of Inappropriate Antidiuretic Hormone (SIADH).Journal of personalized medicine · 2021Article
- Psychotropic drug-induced hyponatremia: results from a drug surveillance program-an update.Journal of neural transmission (Vienna, Austria : 1996) · 2021Article
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Authors and funding
11 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet been explained.
methodsWe investigated the relationship between pharmacological targets of antipsychotic drugs and the occurrence of hyponatremia by conducting a nested case-control study using the Food and Drug Administration Adverse Event Reporting System database. Multiple logistic regression was used to determine the associations between antipsychotics receptor occupancy and hyponatremia. We also performed a systematic review of clinical studies on this association.
resultsOf 139 816 reports involving at least 1 antipsychotic, 1.1% reported hyponatremia. Olanzapine was the most frequently suspected drug (27%). A significant positive association was found between dopamine D3, D4, and hyponatremia, while adrenergic α 1, serotonin 5-HT1A, and 5-HT2A receptor occupancies were negatively associated. A multivariable stepwise regression model showed that dopamine D3 (adj. odds ratio = 1.21; 95% CI = 1.09-1.34; P < .05) predicted the risk for hyponatremia (P < .05), while serotonin 5-HT2A occupancy (Adj. odds ratio = 0.78; 95% CI = 0.68-0.90; P < .01) exhibited a protective effect against hyponatremia. Among the 11 studies included in the systematic review, incidence rates of hyponatremia diverged between 0.003% and 86%, whereas the odds of developing hyponatremia from effect studies ranged between 0.83 and 3.47.
conclusionsAntipsychotic drugs having a combined modest occupancy for D3 and 5-HT2A receptors and higher levels of D3 receptor occupancy correspond to different degrees of risk for hyponatremia. Based on the few, relatively large-scale available studies, atypical antipsychotics have a more attenuated risk profile for hyponatremia.
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