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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
N/A Insufficient evidence to suggest that any significant nutrient depletions exist

Results for Sertraline: 2

Evidence Rating Scale

Folate

Summary: Leucovorin appears to be modestly effective as an adjunct among SSRI-refractory depressed individuals with normal folate levels. The application of leucovorin as an adjunct in the setting of refractory depression deserves further study.

Leucovorin appears to be modestly effective as an adjunct among SSRI-refractory depressed individuals with normal folate levels. The application of leucovorin as an adjunct in the setting of refractory depression deserves further study.

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.

Practitioners should be on the alert for this potentially life-threatening adverse event, especially in older adults with other risk factors for developing hyponatremia.

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.

These results indicate that, among patients with MDD, SSRIs treatment may be associated with decreased serum sodium levels, and the elderly patients are at greater risk for hyponatremia. Further prospective studies would help clarify the relative risks of hyponatremia among various antidepressants.

These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.

Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.

We found no relationship between maximum sertraline dose, age, and changes in routine blood chemistry results with the exception of a small (0.5%) contribution of maximum sertraline dose to variance in serum creatinine levels. Sertraline therapy was not noted to cause any significant changes in serum sodium levels.

We report three cases of severe hyponatraemia, seen in the past 12 months, associated with the selective serotonin reuptake inhibitors fluoxetine and sertraline. Hyponatraemia has been reported as a rare adverse effect of selective serotonin reuptake inhibitors.

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.

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.

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.

Dermatological reactions, fatigue, hyponatraemia and cough were more common in women, whereas dyskinesias/akathisia and aggression more often were seen in men. The median SSRI dosages were above average in patients experiencing seizures, hypomania/mania, personality changes, malaise, bodyweight gain, gynaecomastia and hyperprolactinaemia/galactorrhoea. Severe symptoms, such as seizures, hyponatraemia and the serotonin syndrome, were rarely reported.

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.

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