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Initial Severity and Depressive Relapse in Cognitive Behavioral Therapy and Antidepressant Medications: An Individual Patient Data Meta-analysis

Abstract

Background

Baseline severity has emerged as a key predictor of acute response to treatments for depression. The goals of this individual patient data meta-analysis were to compare the relapse prevention effects of acute phase cognitive behavioral therapy (CBT) vs. acute phase antidepressant medications (ADM) either continued (-c) or discontinued (-d) and determine whether baseline depression severity moderated these effects.

Methods

We included all available relevant randomized trials of CBT versus ADM in adult outpatients with depression. Cox proportional hazards models were used to examine whether treatment condition, baseline severity, and additional characteristics were associated with relapse.

Results

Using individual participant data from 5 of 10 published trials (N = 341), CBT (HR = 0.38, 95% CI 0.26–0.57) and ADM-c (HR = 0.48, 95% CI 0.29–0.80) were superior to ADM-d in preventing relapse over 12 months but did not differ from each other (HR = 1.26, 95% CI 0.76–2.09). Baseline severity did not moderate these effects.

Conclusions

Regardless of a patient’s baseline symptom severity, CBT and ADM-c both prevent depressive relapse substantially better than medication discontinuation. Given the shorter duration of treatment and equivalent longer-term outcomes, treatment with CBT might be considered a first choice for adults with depression.

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Fig. 1
Fig. 2

Data Availability

The datasets generated during and/or analyzed during the current study are available from the authors on reasonable request.

Notes

  1. It has become conventional to distinguish “relapse,” defined as the return of symptoms following remission, from “recurrence,” defined as a new episode following recovery (Frank, et al., 1991) But, the validity of precise criteria for differentiating between relapse and recurrence has not been well established, and it can be difficult in practice to determine when an individual has “recovered” from an index episode. Because we are interested in the effect of severity on symptom return at any point following the end of acute treatment, we do not make distinctions between relapse and recurrence in our analyses, using “relapse” as a universal term for the return of depressive symptoms following acute phase treatment.

  2. Due to the expected small number of RCT’s comparing CBT to medications, the inclusion criteria were intentionally broad. For example, eight sessions is a relatively short and non-standard treatment length and a follow-up of only 6 months is relatively brief. All identified trials had longer durations of acute treatment (10–24 weeks) and longer follow-up (8 to 18 months) than the minimum criteria. Also, the inclusion criteria allowed no more than 5 booster sessions, however, of the included trials only one offered booster sessions and the maximum number offered was 3 (Hollon et al., 2005). There is a small inconsistency in the original registration between the inclusion criteria, which indicates that anyone receiving ADM who is then followed will be included, and the “comparison condition”, which mentions only those who received ADM acutely and were later withdrawn onto placebo. Given the small number of studies and given that our intention was to capture as many trials as possible, we use the stated inclusion criteria throughout and consider for the ADM-d group anyone who was withdrawn from ADM during follow-up.

  3. We use the term “follow-up” to refer to the phase of each study that took place immediately following acute treatment. Some of the studies used other terms to label this phase, e.g., “continuation phase.” Three of the studies (Dobson et al., 2008; Hollon et al., 2005; Jarrett et al., 2000) terminated all continuation treatments at the end of this phase and continued to follow participants naturalistically for another year or more. Those data were not included in the current report as the arms of the naturalistic portions of those studies no longer matched the arms in the “follow-up” phase.

  4. The non-significant difference between CBT and ADM-c represented a small effect (NNT = 16) and power to detect a difference of this magnitude was low in this sample. Conservatively, total samples of > 1800 would be needed to detect an effect of this magnitude given the observed overall relapse rates (SAS PROC POWER; Hsieh & Lavori, 2000).

Abbreviations

IPDMA:

Individual patient data meta-analysis

CBT:

Cognitive behavioral therapy

ADM:

Antidepressant medication

ADM-c:

Acute phase ADM followed by continuation phase ADM

ADM-d:

Acute phase ADM that was discontinued

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Acknowledgements

We would like to the thank the full research teams that aided in the conduct of the trials that provided data for this manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JCF, NRF, ZW, ZL, and SI. The first draft of the manuscript was written by JCF and NRF, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jay C. Fournier.

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Conflict of Interest

Dr. Fournier receives royalties from Guilford Press and has served as paid consultant to Happify, Inc. Dr. Forand has common stock options in AbleTo, Inc. Dr. Jarrett is a paid reviewer for UpToDate and a paid consultant to the National Institutes of Health. She has equity stock in Amgen, Johnson and Johnson, and Procter and Gamble. Dr. Jarrett’s medical center collects the payments from the cognitive therapy she provides to patients. Dr. Vittengl is a paid reviewer for UpToDate. Dr. Shelton reports consulting relationships with: Acadia Pharmaceuticals, Allergan, Inc., Alfasigma USA, Inc., Myriad Neuroscience, Novartis International AG, Evecxia Therapeutics, Janssen Pharmaceutica, Neurorx, Inc., Seelos Therapeutics, Inc.; receiving grant support from: National Institutes of Health, Patient-Centered Outcomes Research Institute, Acadia Pharmaceuticals, Alkermes, Inc., Allergan, Inc., Assurex, Inc., Avanir Pharmaceuticals, Inc., Cerecor, Inc., Genomind, Intracellular Therapies, Janssen Pharmaceutica, LivaNova PLC, Navitor Pharmaceuticals, NeuroRx Inc., Novartis International AG, Otsuka Pharmaceuticals, Takeda Pharmaceuticals; and receiving royalties from UpToDate, Inc./Wolters Kluwer Health. Dr. Dimidjian reports being a co-founder of Mindful Noggin, Inc. receiving revenue from MinfulNoggin.com, receiving royalties from Guilford Press, and receiving funding from philanthropic foundations and the National Institute of Health. No other authors report any conflicts of interest.

Ethical Approval

All studies were performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Included studies were reviewed and approved by the relevant Institutional Review Boards.

Informed Consent All participants provided informed consent to participate to the authors of the trials included in this meta-analysis.

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Fournier, J.C., Forand, N.R., Wang, Z. et al. Initial Severity and Depressive Relapse in Cognitive Behavioral Therapy and Antidepressant Medications: An Individual Patient Data Meta-analysis. Cogn Ther Res 46, 517–531 (2022). https://doi.org/10.1007/s10608-021-10281-x

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Keywords

  • Depression
  • Relapse
  • Cognitive behavioral therapy
  • Antidepressant medication
  • Baseline severity