Electrolyte Disturbances Due to Dual Antidepressants

Electrolyte disturbances, most frequently hyponatremia, were reported for various antidepressant drugs in the past two decades.

Hyponatremia, most probably caused by the syndrome of inappropriate secretion of antidiuretic hormone, has been reported with selective serotonin reuptake inhibitors (SSRIs) in many papers.

Venlafaxine, a dual-action antidepressant, is a serotonin and noradrenaline reuptake inhibitor with a similar mechanism of action to SSRI at low dose. It also increases synaptic norepinephrine and, to a lesser extent, dopamine. Venlafaxine has been shown to cause hyponatremia and it still has to be determined if the risk of hyponatremia is clearly higher in this antidepressant than in SSRIs.

The following risk factors for hyponatremia have been reported during therapy with SSRIs and venlafaxine in several papers: age, female sex, lower body mass index, lower baseline sodium levels, previous history of hyponatremia and concomitant use of other medications known to induce hyponatremia.

In studies with rodents both serotonin and noradrenaline were shown to increase levels of antidiuretic hormone (ADH) by serotonergic and alpha-adrenergic receptors, so one possible mechanism of hyponatremia associated with SSRIs (and venlafaxine) may be stimulation of ADH secretion due to an intensified serotonergic (and noradrenergic) tone after blockade of transporter proteins.

One case of hypokalemia following venlafaxine treatment in a patient suffering from Gitelman syndrome, an inherited renal tubulopathy, has been published.

Mirtazapine, an other dual acting antidepressant, has been observed to cause hyponatremia in one single case report.

A case report of hyponatremia following venlafaxine treatment and recurrence after rechallenge by mistake of the patient will be presented.