A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression

Abstract

Introduction

For patients who continue to experience depressive symptoms despite an adequate antidepressant SSRI trial, across-class switch is considered one of the best treatment options. The goal of the present work was to compare in terms of efficacy two different dual-action compounds, duloxetine and bupropion, in patients who failed to respond in two consecutive antidepressant trials with SSRIs.

Methods

The patients were allocated randomly to duloxetine (120 mg daily) or bupropion extended release (300 mg daily). The intended medication period was 6 weeks. The primary measure of efficacy was depressive symptoms severity.

Results

A total of 49 participants were randomly assigned to duloxetine 120 mg (n = 27) or bupropion 300 mg (n = 22). The ITT efficacy patient sample consisted of 46 patients. Relatively high response and remission rates in treatment groups were found: from 60 to 70% of patients responded to treatment, and approximately 30 to 40% were in remission by the endpoint (week 6). No statistically significant difference emerged between the two groups at any post-baseline assessment, neither on mean scores of rating scales nor on qualitative efficacy measures.

Limits

Limitations of the study are the lack of a placebo arm, difficult to include owing to ethical reasons, and the relatively small size of the sample.

Conclusions

These preliminary results seem to support the hypothesis that in patients unresponsive to SSRIs the administration of antidepressants with different mechanisms of action is an effective switching strategy. Further studies are needed in light of the challenge posed by resistant depression.

Introduction

Treatment-resistant depression continues to represent a major challenge for clinicians: only 50 to 60% of patients respond to the first antidepressant given (Kroenke et al., 2001). Switching to a different monotherapy antidepressant medication is the preferred option for many patients and clinicians. The possible advantages of switching to a different monotherapy, as compared with adding a second agent (i.e., augmenting or combining), include reduced medication costs, fewer drug interactions, better adherence, and less patient burden over time (Marangell, 2001). In addition, switching to a different antidepressant may be quite appealing to patients, especially when the alternative drug has a more acceptable side effect profile (Fava, 2000, Fava and Rush, 2006).

There are two major types of switching strategies studied in literature: within-class switch and across-class switch. Recently, level 2 of the STAR*D trial compared switching patients with no remission of symptoms from citalopram to bupropion, sertraline or venlafaxine: no differences in efficacy or tolerability emerged between the three treatment groups, with remission rates across treatments of approximately 25% (Rush et al., 2006). The results of a recent meta-analysis conducted by Papakostas et al. suggest a modest yet statistically significant advantage in remission rates when switching patients with SSRI-resistant depression to a non-SSRI rather than an SSRI antidepressant (Papakostas et al., 2008): it is, however, a limitation that only three non-SSRIs (venlafaxine, mirtazapine, and bupropion) were included in the meta-analysis and that most of the studies involved venlafaxine, with the advantage noted being evident regardless of whether or not the two comparisons that utilized mirtazapine and bupropion were included.

Respect to switching strategies from SSRIs to duloxetine, data are limited: an open-label trial conducted on a sample of 40 elderly subjects who have not responded to escitalopram, suggest that duloxetine at doses up to 120 mg/day is a potentially effective and well-tolerated treatment (Karp et al., 2008). In addition, the results of a multicentre trial comparing two different switching strategies from SSRIs to duloxetine (direct switch or start-taper switch) in patients with major depression suggest significant improvements in both emotional and painful physical symptoms of depression regardless of which of the switch methods was used (Perahia et al., 2006).

On the basis of these findings, we hypothesize that, in patients unresponsive to SSRIs, the administration of an antidepressant with a different mechanism of action may be an effective switching strategy. The aim of this study is to compare the efficacy of two different dual-action compounds, duloxetine and bupropione, in patients with major depression unresponsive to SSRIs.