Antidepressants Associated

Antidepressants Associated With Hyponatremia

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TAKE-HOME MESSAGE

  • A cohort of 638,352 people was evaluated from 1998 through 2012 to investigate the relationship between the use of antidepressants and the risk of hyponatremia. The incidence rate ratio for the association with hyponatremia after initiation of treatment was highest for citalopram (7.80) and lowest for mianserin (0.90). The incidence rate ratio for other agents were: clomipramine 4.93, duloxetine 2.05, venlafaxine 2.90, and mirtazapine 2.95.
  • Apart from mianserin, all antidepressant agents are associated with an increased risk of hyponatremia, with the highest risk seen with citalopram.

Antidepressants are associated with the development of several metabolic abnormalities. This study reports an association between antidepressants and the development of hyponatremia. With the wide use of antidepressants such as SSRIs and SNRIs, it is important to remember to monitor patients periodically on such medications for electrolyte disturbances, glucose intolerance, and lipid abnormalities. Elderly patients are especially at risk and may warrant closer monitoring as the use of other chronic medications and decreased renal clearance may further increase the risk for hyponatremia.

OBJECTIVE

To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.

DESIGN

Retrospective register-based cohort study using nationwide registers from 1998 to 2012.

SETTING

The North Denmark Region.

PARTICIPANTS

In total, 638 352 individuals were included.

PRIMARY AND SECONDARY OUTCOME MEASURES

Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models.

RESULTS

An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14).

CONCLUSIONS

All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.