Abstract

BackgroundPatients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure. Recently, we did not find differences in outcomes in non-improvers randomized to an early medication change (EMC) strategy compared to treatment as usual (TAU). This secondary analysis investigated possible predictors of higher remission rates in the EMC strategy.MethodsOf 192 non-improvers (i.e. decrease of ≤20% on the HAMD-17 depression scale) after a two-week treatment with escitalopram, n = 97 were randomized to EMC (immediate switch to high doses of venlafaxine XR) and n = 95 to TAU (continued escitalopram until day 28 with non-responders switched to venlafaxine XR). We first analyzed patient characteristics, psychopathological features and subtypes of MDD by logistic regression analyses as possible predictors of remission rates. In a second investigation, we analyzed the predictors, which showed a significant association in the first analysis before Bonferroni-Holm correction by chi-squared tests separated for treatment groups. All analyses were corrected by Bonferroni-Holm method.ResultsThe first analyses yielded no statistically significant results after correction for multiple testing. In the second analyses, however, patients with prior medication at study entry showed higher remission rates in EMC than in TAU (24.2% versus 8.6%, p = 0.017; Bonferroni-Holm corrected significance level: p = 0.025.). Furthermore, patients with a recurrent course of MDD benefited less from treatment as usual (p = 0.009; Bonferroni-Holm corrected significance level: p = 0.025). Age, sex, age of onset, psychiatric or somatic comorbidities, and other subtypes of MDD did not predict remission rates.ConclusionsAlthough in our first analysis we found statistically non-significant results, the second analysis showed significant differences in remission rates between patients with or without previous medication and in patients with recurrent MDD or the first depressive episode. It would therefore be valuable to examine in larger and prospective studies whether remission rates can be increased by quick escalation of treatment in certain subgroups of patients. Promising subgroups to be tested are patients who were previously medicated, and who show a recurrent course of MDD.Trial registrationclinicaltrials.gov Identifier: NCT00974155. Registered at the 10th of September 2009. Retrospectively registered.

Highlights

  • Patients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure

  • Based on this observation we performed a randomized controlled trial with 889 patients to determine whether an early medication change (EMC) strategy is superior to a guideline based treatment in MDD patients with non-improvement after two weeks of antidepressant treatment

  • As previously published [18], demographic and clinical characteristics of patients randomized to EMC or treatment as usual (TAU) were comparable at baseline

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Summary

Introduction

Patients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure. We did not find differences in outcomes in non-improvers randomized to an early medication change (EMC) strategy compared to treatment as usual (TAU). This secondary analysis investigated possible predictors of higher remission rates in the EMC strategy. Patients who do not show more than 20% improvement after two weeks of antidepressant treatment, have a high risk of later treatment failure ([13, 14], see [15]) Based on this observation we performed a randomized controlled trial with 889 patients to determine whether an early medication change (EMC) strategy is superior to a guideline based treatment in MDD patients with non-improvement (defined as a reduction of ≤20% on the HAMD-17) after two weeks of antidepressant treatment. The results did not confirm the merits of the switch/adjunct therapy strategy, as only 24% of patients remitted according to the Hamilton Rating Scale for Depression (HAMD-17) [17], which was not significantly different form the remission rate in the TAU group [18]

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