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Pharmacopsychiatry 2019; 52(04): 170-174
DOI: 10.1055/a-0643-4796
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

A Novel Study Design to Systematically Explore the Impact of Trial Methodology on Psychopharmacological Treatment Outcome in Patients with Depression

Emanuel Severus
1   Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Cathrin Sauer
1   Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Michael Bauer
1   Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Michael Ostacher
2   Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
,
Ion-George Anghelescu
3   Privat-Nervenklinik Dr. Med. Kurt Fontheim, Liebenburg, Germany
› Author Affiliations
Further Information

Publication History

received 04 February 2018
revised 04 June 2018

accepted 07 June 2018

Publication Date:
05 July 2018 (online)

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Abstract

Introduction Randomized, double-blind, placebo-controlled trials were developed to draw rather unbiased conclusions regarding the efficacy of antidepressants in the treatment of a major depressive episode (internal validity), mostly with the purpose of formal approval of new compounds in this indication. However, at the same time, data suggest that the very process of randomization and blinded administrations of placebo will have a significant impact on the efficacy of the antidepressant tested and therefore may limit the external validity of results obtained from this type of studies. Therefore, there is an urgent need to systematically study the impact of randomization/placebo control/blinding on patient population, efficacy, tolerability, and external validity in the psychopharmacological treatment of patients with a major depressive episode.

Methods To develop a study design that allows the systematic exploration of the impact of trial design on characteristics of included patient population and outcome.

Results We propose a study design including sample size calculation and statistical analysis in which patients with a major depressive episode are randomized to 3 distinct study designs that differ with regard to control, randomization, and blindness.

Discussion The results of the proposed study design may have substantial consequences when it comes to how to best interpret the results of traditional randomized, double-blind, placebo-controlled trials in the acute treatment of major depressive disorder. Furthermore, they may lead to the implementation of new study designs that may be more suitable for assessing the effectiveness of new antidepressant compounds in everyday clinical practice.

Key words

antidepressant - random allocation - trial design - randomized controlled trials as topic - major depressive disorder
 

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