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Meta-Analysis
. 2024 Feb 26;67(1):e20.
doi: 10.1192/j.eurpsy.2024.11.

The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds

Tim Gheysens  1   2 , Filip Van Den Eede  1   3 , Livia De Picker  1   2
Affiliations
Meta-Analysis

The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds

Tim Gheysens et al. Eur Psychiatry. .

Abstract

Background: Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

Methods: A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801.

Results: We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa.

Conclusion: Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Keywords: adverse drug events; antidepressive agents; hyponatremia; inappropriate ADH syndrome; psychiatry.

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Conflict of interest statement

The authors declare none.

Figures

Figure 1.
Figure 1.
PRISMA flowchart of study inclusion process.
Figure 2.
Figure 2.
Forest plot summarizing ORs and aORs for any hyponatremia (<135 mmol/L) during treatment with SNRIs, SSRIs, TCAs, MAOIs, and mirtazapine compared to no antidepressant.
Figure 3.
Figure 3.
Forest plot for any hyponatremia during treatment with SNRIs compared to SSRIs.
Figure 4.
Figure 4.
Forest plot for any hyponatremia during treatment with mirtazapine compared to SSRIs.
Figure 5.
Figure 5.
Forest plot for clinically relevant hyponatremia during treatment with mirtazapine compared to SSRIs.
See this image and copyright information in PMC

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