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Relapse and recurrence prevention in major depression: a critical review of placebo-controlled efficacy studies with special emphasis on methodological issues

Published online by Cambridge University Press:  16 April 2020

J.G. Storosum ,
B.J. van Zwieten ,
H.D.B. Vermeulen ,
T. Wohlfarth  and
W. van den Brink
J.G. Storosum*
Affiliation:
Medicines Evaluation Board of the Netherlands Den Haagthe HagueThe Netherlands Psychiatric Department of the Academic Medical Centre University of Amsterdam, Tafelbergweg 25Amsterdam, 1105 BC Amsterdam The Netherlands
B.J. van Zwieten
Affiliation:
Medicines Evaluation Board of the Netherlands Den Haagthe HagueThe Netherlands
H.D.B. Vermeulen
Affiliation:
Psychiatric Department of the Academic Medical Centre University of Amsterdam, Tafelbergweg 25Amsterdam, 1105 BC Amsterdam The Netherlands
T. Wohlfarth
Affiliation:
Medicines Evaluation Board of the Netherlands Den Haagthe HagueThe Netherlands
W. van den Brink
Affiliation:
Medicines Evaluation Board of the Netherlands Den Haagthe HagueThe Netherlands
*
* Correspondence and reprints: E-mail address: [email protected] (J.G. Storosum).
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Summary

This article critically reviews the design and methodology of studies aimed at evaluating relapse and recurrence prevention in major depression. A literature search in MEDLINE was performed with the medical subject headings ‘depression’, ‘recurrence’, ‘relapse’, ‘prevention’ and ‘study’. This search covered the period from January 1990 to July 1999. Only long-term placebo-controlled studies that included patients with non-chronic major depression were selected. Two types of design could be distinguished: randomised withdrawal studies in responders/remitters (N = 11) and extension studies in responders without re-randomisation (N = 3).

Randomised withdrawal studies are suitable for demonstrating long-term efficacy for the duration of the study period. However, this design does not permit a clear differentiation between relapse or recurrence and, therefore, is not suitable to demonstrate unequivocally relapse prevention or recurrence prevention. Extension studies in short-term responders without randomisation are not even suitable to demonstrate long-term efficacy.

A novel design is proposed that overcomes the weaknesses of designs employed thus far. In essence, this design calls for a long-term randomised placebo-controlled study in patients who are free of medication for a substantial period of time and who fulfil the criteria of major depression (recurrent) in sustained remission (e.g., HDRS < 7) as a possible option.

Keywords

long-term efficacymajor depressionmethodologyrecurrencerelapse
Type
Original Article
Information
European Psychiatry , Volume 16 , Issue 6 , September 2001 , pp. 327 - 335
Copyright
Copyright © 2001 Éditions scientifiques et médicales Elsevier SAS. All rights reserved

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