Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Switching to Imipramine Versus Add-on Mirtazapine in Venlafaxine-Resistant Major Depression

A 10-Week Randomized Open Study

Navarro, Víctor, PhD*; Boulahfa, Ilham, MD; Obach, Amadeu, PsyD*; Jerez, Dídac, MD; Diaz-Ricart, Maribel, PhD; Gastó, Cristóbal, PhD*; Guarch, Joana, PhD*

Journal of Clinical Psychopharmacology: January/February 2019 - Volume 39 - Issue 1 - p 63–66
doi: 10.1097/JCP.0000000000000988
Brief Reports

Purpose/Background Newer-generation antidepressants used in monotherapy or in combination with other newer-generation antidepressants or other psychotropic drugs are usually preferred as first- or second-step treatment options in resistant depression. According to our clinical experience, tricyclic antidepressants still are one of our preferred first choices in treatment-resistant moderate to severe unipolar major depressive episodes.

Methods This 10-week open-design randomized study assessed the effectiveness of switching to imipramine (adjusted to plasma levels) compared with add-on mirtazapine (30 mg/d) for treatment of moderate to severe unipolar major depressive episodes after a 10-week unsuccessful venlafaxine regimen (225–300 mg/d). Efficacy analyses examined the change in depressive symptoms severity from baseline visit to endpoint and the comparative remission rate between treatment subgroups.

Findings/Results The randomized sample consisted of 112 venlafaxine-resistant moderate to severe unipolar major depressed patients. Both the percentage of remitters (71.43% vs 39.28%) and the mean reduction of the Hamilton Depression Rating Scale score (76.94% vs 50.72%) were significantly larger in the imipramine subgroup.

Implications/Conclusions Even though we should be cautious about generalizing these results to patients with a less severe unipolar major episodes, our study suggest that switching to imipramine is a very effective treatment option in unipolar major depressive episodes after an unsuccessful venlafaxine regimen.

From the *Department of Psychiatry and Clinical Psychology, Hospital Clinic of Barcelona, IDIBAPS, CIBERSAM;

Research, Innovation and Teaching Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat (Barcelona); and

Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, IDIBAPS, UB, University of Barcelona, Barcelona, Spain.

Received May 18, 2018; accepted after revision November 2, 2018.

Reprints: Víctor Navarro, PhD, Unipolar Mood Disorder Program, Hospital Clínic de Barcelona, Villarroel 170, 08036 Barcelona, Spain (e-mail:

This study was partially supported by the Instituto de Salud Carlos III (ISCIII): Fondo de Investigación Sanitaria (FIS-PI13/00517).

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.