Psychotropic drug-induced hyponatremia: results from a drug surveillance program–an update

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.

Identification of risk factors associated with hyponatremia in psychiatric patients: a case-control study

“…The prevalence of SIADH has been estimated to be as high as 11% in acutely ill psychiatric patients [ 14 ]. A drug surveillance program reported that the highest incidence of hyponatremia was found in antiepileptic drug users when compared to all other psychotropic drugs [ 15 ].…”

Pathophysiology of Drug-Induced Hyponatremia

“…Causality between antidepressants and hyponatremia was more frequently shown with SSRIs than with others. According to a drug surveillance program performed in Germany and Austria, SSRIs and SNRIs presented the highest risk of hyponatremia among antidepressants [ 48 ]. Of the SSRIs available, fluoxetine, paroxetine, and sertraline are the more common offenders.…”

“…Oxcarbazepine is a keto-analog of carbamazepine and may be more associated with hyponatremia than carbamazepine [ 48 ]. Sachdeo et al investigated the mechanisms by which oxcarbazepine induces hyponatremia in epilepsy and healthy subjects [ 66 ].…”

Potential Use of Pharmacogenetics to Reduce Drug-Induced Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

“…In clinical practice, however, the strength of association between opioids and SIADH does not appear to approach the magnitude of the association between SSRIs and SIADH [ 26 ]. Another class of drugs strongly associated with SIADH has been the anti-seizure drugs [ 27 ]. Carbamazepine and oxcarbazepine cause hyponatremia quite often [ 28 ].…”