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Randomized Controlled Trial
. 2019 Jan 14;19(1):24.
doi: 10.1186/s12888-019-2014-x.

Predictors of the effectiveness of an early medication change strategy in patients with major depressive disorder

Nadine Dreimüller  1 , Stefanie Wagner  2 , Alice Engel  2 , Dieter F Braus  3 , Sibylle C Roll  4 , Stefan Elsner  5 , André Tadić  2   6 , Klaus Lieb  2
Affiliations
Randomized Controlled Trial

Predictors of the effectiveness of an early medication change strategy in patients with major depressive disorder

Nadine Dreimüller et al. BMC Psychiatry. .

Abstract

Background: Patients 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.

Methods: Of 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.

Results: The 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.

Conclusions: Although 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 registration: clinicaltrials.gov Identifier: NCT00974155 . Registered at the 10th of September 2009. Retrospectively registered.

Keywords: Antidepressant; Early improvement; Major depressive disorder; Predictor; Treatment outcome.

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Conflict of interest statement

Ethics approval and consent to participate

The trial was approved in July 2009 by the ethics committee at the Landesärztekammer Rheinland-Pfalz (code: 837.211.09 (6717)) and the German Federal Institute for Drugs and Medical Devices (BfArM) approved the trial protocol. All study participants provided written informed consent at enrollment into the protocol treatment. The study was conducted in accordance with the Helsinki Declaration and is compliant with the CONSORT guidelines.

Consent for publication

Not applicable

Competing interests

AT has received consultancy fees from Janssen and Novartis. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a-c: Remission rates at endpoint in patients randomized to EMC or TAU. a: In relation to prior medication. a: MDD: Major depressive disorder; EMC: Early Medication Change; TAU: Treatment as usual; * difference in remission Chi2-Test (df = 1) bold if significant. TAU arm: remission in patients with prior medication (8.6%), remission in patients without prior medication 24.3% p = 0.017. Bonferroni-Holm corrected significance level p = 0.025. In the EMC Arm: remission in patients without prior medication 17.1%, remission in patients with prior medication 31.2%; Chi2 = 0.656; df = 1; p = 0.456, Bonferroni-Holm corrected significance level: p = 0.025. b: In relation to a recurrent course of MDD or first episode. b: MDD: Major Depressive Disorder; EMC: Early Medication Change; TAU: Treatment as usual; * difference in remission Chi2-Test (df = 1) bold if significant. TAU-arm: remission in patients with recurrent MDD 7.6%, patients with first episode 31% p = 0.009; Bonferroni-Holm corrected significance level: p = 0.025. EMC-arm: remission in patients with recurrent MDD 22.1%, patients with first episode 20.6% p = 0.028; Bonferroni-Holm corrected significance level: p = 0.025; n.s. c: In relation to the presence of atypical MDD. c: MDD: Major Depressive Disorder; EMC: Early Medication Change; TAU: Treatment as Usual; * significant difference in remission Chi2-Test (df = 1) bold if significant. TAU-arm: remission in patients with patients with atypical MDD 27.8%, patients without atypical features 8.1% p = 0.028; Bonferroni-Holm corrected significance level: p = 0.025, n.s. EMC-arm: remission in patients with patients with atypical MDD 20.6%, patients without atypical features 22.6% p = 0.558; Bonferroni-Holm corrected significance level: p = 0.025; n.s
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