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Level Qualifying studies
A Systematic review or meta-analysis of human trials
B Human RDBPC trials. ≥ 2 studies and/or 1 study with ≥ 50 subjects
C Human RDBPC trials or RCTs. 1 study < 50 subjects
D Human trials or in-vivo animal trials
G No significant nutrient depletion research was found

Results for Citalopram: 2

Evidence Rating Scale

Melatonin

Summary: A 47% increase in melatonin suppression was observed after administration of an acute dose of citalopram, with all participants showing more suppression after citalopram administration. Further, melatonin onset occurred later under normal room light with citalopram compared to placebo.

A 47% increase in melatonin suppression was observed after administration of an acute dose of citalopram, with all participants showing more suppression after citalopram administration. Further, melatonin onset occurred later under normal room light with citalopram compared to placebo.

Sodium

Summary: Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature.Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.

Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature.Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.

Numerous studies have reported hyponatremia associated with SSRI use, with the incidence varying from 0.5% to 32%. Risk factors for the development of hyponatremia with SSRIs include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration. In published reports, hyponatremia developed within the first few weeks of treatment and resolved within 2 weeks after therapy was discontinued.

In elderly patients, the prevalence of hyponatremia as adverse reaction to all types of antidepressants was 9%. Patients with previous hyponatremia, weight <60 kg, and psychosis were at risk. Beside SIADH, the nephrogenic syndrome of inappropriate antidiuresis, in which ADH secretion was normal, is postulated as an underlying mechanism. This has consequences for treatment of antidepressant-induced hyponatremia with vasopressin receptor antagonists.

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

Three selective serotonin reuptake inhibitors (citalopram, escitalopram, and fluoxetine) were associated with significantly increased risks of hyponatraemia, but paroxetine and sertraline were not. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls and hyponatraemia compared with when antidepressants were not being used.

Three selective serotonin reuptake inhibitors (citalopram, escitalopram, and fluoxetine) were associated with significantly increased risks of hyponatraemia, but paroxetine and sertraline were not. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls and hyponatraemia.

Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia.

These data suggest that antidepressant treatment is associated with hyponatraemia affecting a subgroup of individuals only. Generalised linear modelling showed that the risk of hyponatraemia increases with increased age, female gender, and particularly the antidepressant agents sertraline and escitalopram. The findings are of clinical significance as they demonstrate that hyponatraemia can occur rapidly with antidepressants, and SSRI/SNRI medications induce more rapid changes. They support the use of electrolyte monitoring early in antidepressant treatment in patients receiving antidepressants.

There was a strong association between newly initiated treatment with SSRIs or venlafaxine and hospitalization due to hyponatremia. The association for tricyclic antidepressants and mirtazapine was small to moderate. In contrast, there was no evidence that ongoing treatment with antidepressants increases the risk for hospitalization due to hyponatremia.

Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.

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