Is there any difference in the incidence of hyponatremia during treatment with different selective

Fråga: Is there any difference in the incidence of hyponatremia during treatment with different selective serotonin reuptake inhibitors (SSRI)? The question pertains to an 80-year-old man that has been treated with sertraline (Zoloft) for some years due to depression. Now the patient has developed hyponatremia, a recognised adverse effect of sertraline. The psychiatrist asks whether there are any other SSRI that are not associated with hyponatremia.

Sammanfattning: All SSRI have been associated with hyponatremia. Data do not reliably suggest a different incidence for different SSRIs at equivalent doses. Also the tricyclic antidepressants might in rare cases cause hyponatremia. In contrast, mianserin and mirtazapine does not seem to be associated with this adverse reaction, although there are a few case-reports about hyponatremia for these substances too.

Svar: All SSRI have been associated with hyponatremia. Reliable frequency figures are not available, but there is no obvious difference between different agents (1,2). Furthermore, SSRI have rarely been associated with the syndrome of inappropriate ADH-secretion (SIADH). SIADH is characterized by an excessive ADH activity, leading to water-retention, hypotonic water-intoxication and hyponatremia. The mechanism by which SSRI might induce SIADH is unclear (3). Some studies imply that the SSRI-induced increase of intracerebral serotonin levels might affect ADH expression and secretion (4,5). However, the scientific literature is not consistent on this point, and other studies have not been able to substantiate that serotonin would have an effect on the expression and secretion of ADH (6).

In most described cases, patients with SSRI-associated SIADH have developed hyponatremia during the first weeks of SSRI-medication or after dose-adjustment. The risk of SSRI-associated hyponatremia is more pronounced in elderly patients and patients treated with diuretics (1,7).

The tricyclic antidepressants have also rarely been associated with SIADH and hyponatremia. However, the tetracyclic antidepressants, mianserin and mirtazapin, do not seem to have been convincingly associated with hyponatremia (1,2,8). These substances have a presynaptic alfa-antagonistic effect that increases the noradrenergic and (for mirtazapine) the serotonergic neurotransmission in the CNS. The different mechanisms of action of the tetracyclic antidepressants and the SSRIs might explain a difference in the likelihood of developing SIADH, although there is no hard evidence for this.

In the Swedish adverse-reaction-report database SWEDIS, reports dealing with SSRI and hyponatremia constitute approximately 3.5% of the total number of reports concerning SSRI (9). Also for mirtazapine there are a few case-reports of hyponatremia (4 of 498 reports). For mianserin there are a total of 406 adverse-reaction-reports, one of which concerns SIADH (9).