Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase


  • Location of work: Psychiatric Hospital, Priazha District, Republic of Karelia, Russia; Psychoneurological Dispensary, Krasnoflotskaya Street 29, Petrozavodsk, Republic of Karelia, Russia.

V. Terevnikov, MD, PhD, Kellokoski Hospital, 04500, Kellokoski, Finland. E-mail:


Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial.

Patients (n = 41) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase. Efficacy measures were the Calgary Depression Scale for Schizophrenia (CDSS) and the Positive and Negative Syndrome Scale depression item.

During the double-blind phase, both measures' scores decreased significantly in the mirtazapine group but not in the placebo group (for the CDSS, 52.0% vs 19.6%, respectively). During the open-label phase, both groups demonstrated significant improvements. In between-group comparison, a trend favoring mirtazapine did not reach statistical significance. The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative, positive and total (sub)scales for mirtazapine-treated patients during the double-blind phase.

Depressed patients with schizophrenia may benefit from mirtazapine–first-generation antipsychotics combination, with no increased risk for psychosis. However, more studies are needed. Copyright © 2011 John Wiley & Sons, Ltd.