Mirtazapine augmentation in the treatment of refractory depression

Pharmacotherapeutic strategies that target specific actions at multiple neuronal receptors or cellular components may offer a superior approach for treatment of refractory depression. Mirtazapine is a novel antidepressant which has a mechanism that involves the enhancement of noradrenergic and serotonergic neurotransmission via blockade of alpha2-adrenergic autoreceptors and heteroreceptors without activity at the serotonin transporter. Mirtazapine is thus a compelling candidate for augmentation treatment in patients who fail to achieve adequate response with other antidepressant medications.

Twenty patients with DSM-IV major depression or dysthmia who had persistent depressive syndromes despite at least 4 weeks of standard antidepressant pharmacotherapy were given augmentation with mirtazapine (15 to 30 mg p.o. q.h.s.) on an open-label basis. Clinical assessments of status at baseline, 2 weeks, and 4 weeks were used to rate response.

Forty-five percent (N = 9) of the sample were responders at 2 weeks. At the 4 week follow-up, 55% (N = 11) were responders, 30% (N = 6) were nonresponders, and 15% (N = 3) had discontinued treatment owing to side effects. Common side effects included weight gain and sedation.

These data suggest that the addition of mirtazapine may be beneficial for patients who have refractory depression, but side effects are prominent at the doses we used. Controlled trials to further evaluate the efficacy and safety of mirtazapine augmentation are needed.