Psychotropic drug-induced hyponatremia: results from a drug surveillance program\u2013an update

Johanna Seifert,Timo Greiner,Christian K Eberlein,Maximilian Deest,Sermin Toto,Stefan Bleich,Michael Schneider,Renate Grohmann,Martin Letmaier

doi:10.1007/s00702-021-02369-1

Abstract

Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of < 130 mmol/l) and often induced by drugs including psychotropic drugs. AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicenter drug surveillance program that assesses severe or unusual adverse drug reactions (ADRs) occurring during treatment with psychotropic drugs. This study presents data from 462,661 psychiatric inpatients treated in participating hospitals between 1993 and 2016 and serves as an update of a previous contribution by Letmaier et al. (JAMA 15(6):739–748, 2012). A total of 210 cases of HN were observed affecting 0.05% of patients. 57.1% of cases presented symptomatically; 19.0% presented with severe symptoms (e.g., seizures, vomiting). HN occurred after a median of 7 days following the first dose or dose increase. Incidence of HN was highest among the two antiepileptic drugs oxcarbazepine (1.661% of patients treated) and carbamazepine (0.169%), followed by selective serotonin-norepinephrine reuptake inhibitors (SSNRIs, 0.088%) and selective serotonin reuptake inhibitors (0.071%). Antipsychotic drugs, tricyclic antidepressants, and mirtazapine exhibited a significantly lower incidence of HN. The risk of HN was 16–42 times higher among patients concomitantly treated with other potentially HN-inducing drugs such as diuretic drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and proton pump inhibitors. Female SSNRI-users aged ≥ 65 years concomitantly using other HN-inducing drugs were the population subgroup with the highest risk of developing HN. The identification of high-risk drug combinations and vulnerable patient subgroups represents a significant step in the improvement of drug safety and facilitates the implementation of precautionary measures.

Highlights

Hyponatremia (HN) is characterized by low serum sodium concentration and is the most common type of electrolyte imbalance (Dineen et al 2017)
N number, HN hyponatremia, 95% confidence intervall (95% CI) 95% confidence interval, ADD antidepressant drug, antipsychotic drugs (APDs) antipsychotic drug, antiepileptic drugs (AEDs) antiepileptic drug, TCAtricyclic antidepressant, selective serotonin reuptake inhibitors (SSRIs) selective serotonin reuptake inhibitor, selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) selective serotonin-norepinephrine reuptake inhibitor, Noradrenergic and specific serotonergic antidepressant (NaSSA) noradrenergic and specific serotonergic antidepressant, monoamine oxidase inhibitors (MAOIs) monoamine oxidase inhibitor, FGA first generation antipsychotic drug, SGA second generation antipsychotic drug, hp high potency, lp low potency explicitly stated otherwise, the following refers to all cases of HN
This study demonstrates that the combined use of pump inhibitors originally associated with hyponatremia (PPIHNs) with SSRIs and SSNRIs each showed a higher risk of HN than when used with the pump inhibitors not originally associated with hyponatremia (PPINNs) pantoprazole

Summary

Introduction

Hyponatremia (HN) is characterized by low serum sodium concentration (generally < 135 mmol/l) and is the most common type of electrolyte imbalance (Dineen et al 2017). HN was set at serum sodium concentration Na(S) below 130 mmol/l, as it is more relevant to clinical practice (Spasovski et al 2014; Mazhar et al 2021). It is estimated that 15–20% of all patients admitted to the hospital suffer from this condition. The severity of symptoms is highly variable ranging from a complete absence of symptoms to mild symptoms such as headache, nausea, and imbalance, to serious symptoms such as seizures, cognitive impairment, and coma. The intensity of symptoms is associated with how quickly Na(S) decreases. A sudden onset drop (< 48 h) of Na(S) causes more dramatic clinical symptoms than a

Methods

Results

Discussion

Conclusion