Prevention of Recurrence After Recovery From a Major Depressive Episode With Antidepressant Medication Alone or in Combination With Cognitive Behavioral Therapy: Phase 2 of a 2-Phase Randomized Clinical Trial

DeRubeis, Robert J.; Zajecka, John; Shelton, Richard C.; Amsterdam, Jay D.; Fawcett, Jan; Xu, Colin; Young, Paula R.; Gallop, Robert; Hollon, Steven D.

doi:10.1001/jamapsychiatry.2019.3900

Cited by 48Treatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesMental Health Treatment and Access

Prevention of Recurrence After Recovery From a Major Depressive Episode With Antidepressant Medication Alone or in Combination With Cognitive Behavioral Therapy: Phase 2 of a 2-Phase Randomized Clinical Trial

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DeRubeis, Robert J., Zajecka, John, Shelton, Richard C., Amsterdam, Jay D., Fawcett, Jan, Xu, Colin, Young, Paula R., Gallop, Robert +1 more·2020·JAMA Psychiatry

DOI 10.1001/jamapsychiatry.2019.3900PMC PMC6902236

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Abstract

Importance: Antidepressant medication (ADM) maintenance treatment is associated with the prevention of depressive recurrence in patients with major depressive disorder (MDD), but whether cognitive behavioral therapy (CBT) treatment is associated with recurrence prevention remains unclear. Objective: To determine the effects of combining CBT with ADM on the prevention of depressive recurrence when ADMs are withdrawn or maintained after recovery in patients with MDD. Design, Setting, and Participants: A total of 292 adult outpatients with chronic or recurrent MDD who participated in the second phase of a 2-phase trial. Participants had recovered in the first phase of the trial receiving ADM, either alone or in combination with CBT. The trial was conducted in research clinics in 3 university medical centers in the United States. Patients in phase 2 were randomized to receive maintenance of or withdrawal from ADM and were followed up for 3 years. The first and last patients entered phase 2 in August 2003 and October 2009, respectively. The last patient completed phase 2 in August 2012. Data were analyzed from December 2013 to December 2018. Interventions: Maintenance of or withdrawal from treatment with ADM. Main Outcomes and Measures: Recurrence of an MDD episode using longitudinal interval follow-up evaluations; sustained recovery across both phases. Results: A total of 292 participants (171 women, 121 men; mean [SD] age 45.1 [12.9] years) were included in analyses of depressive recurrence. Maintenance ADM yielded lower rates of recurrence compared with ADM withdrawal regardless of whether patients had achieved recovery in phase 1 with ADM alone (48.5% vs 74.8%; z = -3.16; P = .002; number needed to treat [NNT], 2.8; 95% CI, 1.8-7.0) or ADM plus CBT (48.5% vs 76.7%; z = -3.49; P < .001; NNT, 2.7; 95% CI, 1.9-5.9). Sustained recovery rates differed as a function of phase 2 condition, with maintenance ADM superior to ADM withdrawal (z = 2.90; P = .004; OR, 2.54; 95% CI, 1.37-4.84; NNT, 2.3; 95% CI, 1.5-6.4). Phase 1 condition was not associated with differential rates of sustained recovery (ADM alone vs ADM plus CBT; z = 0.22; P = .83; OR, 1.08; 95% CI, 0.52-2.11; NNT, 26.0; 95% CI, number needed to harm 3.2 to NNT 2.8), nor was there a significant interaction of phase 1 condition and phase 2 condition (z = 0.30; P = .77; OR, 1.14; 95% CI, 0.49-2.88). Conclusions and Relevance: Maintenance ADM treatment, but not previous exposure to CBT, was associated with reduced rates of depressive recurrence. In previous studies, when CBT has been provided without ADM, CBT has shown a preventive effect on depressive relapse. Whether CBT also has a preventive effect on depressive recurrence, or if adding ADM interferes with any such preventive effect, remains unclear. Trial Registration: ClinicalTrial.gov identifier: NCT00057577.

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Specific forms of CBT and pharmacotherapy focused on relapse prevention have been found to significantly reduce relapse for eating, substance use, mood and anxiety disorders.
“Specific forms of CBT and pharmacotherapy focused on relapse prevention have been found to significantly reduce relapse for eating, substance use, mood and anxiety disorders (246–255).”
From The integrated treatment of eating disorders, posttraumatic stress disorder, and psychiatric comorbidity: a commentary on the evolution of principles and guidelines (2023) · cites this paper as [248]
The Recurrence section (page not provided) reports significantly lower depressive recurrence among patients who continued antidepressant medication than among those withdrawn from it. The Discussion (page not provided) notes benefits of relapse-focused psychotherapy in other depression studies, but this trial found no added recurrence protection from CBT. The paper does not establish the claimed benefit across eating and substance use disorders. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Between one-fifth and one-half of patients in remission from a depressive episode will suffer a recurrence within 2 years.
“Studies indicate that between one-fifth to one-half of patients in remission from a depressive episode will suffer a recurrence within 2 years.4–10”
From Predicting Relapse of Depressive Episodes During Maintenance Treatment: The Canadian Biomarker Integration Network in Depression (CAN-BIND) Wellness Monitoring in Major Depressive Disorder Study: Prédire la rechute d’épisodes dépressifs pendant le traitement d’entretien : Une étude de suivi du bien-être dans les troubles dépressifs majeurs du Réseau canadien d’intégration des biomarqueurs pour la dépression (CAN-BIND) (2025) · cites this paper as [4]

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Effect of Cognitive TherapyWith AntidepressantMedications vs Antidepressants Alone on the Rate of Recovery inMajor Depressive Disorder A Randomized Clinical Trial
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Authors: DeRubeis, R. J., Zajecka, J., Shelton, R. C., Amsterdam, J. D., Fawcett, J., Xu, C., Young, P. R., Gallop, R., & Hollon, S. D.
Affiliations: University of Pennsylvania (US)
Rush University (US)
Vanderbilt University (US)
University of New Mexico (US)
West Chester University (US)
Corresponding author: DeRubeis, Robert J.
ORCID: DeRubeis, Robert J.
Zajecka, John
Shelton, Richard C.
Xu, Colin
Gallop, Robert
Hollon, Steven D.
Venue: JAMA Psychiatry
Publisher: American Medical Association (AMA)
Published: 2020-03-01
Volume: 77
Issue: 3
Pages: 237
ISSN: 2168-622X (ISSN-L)
DOI: 10.1001/jamapsychiatry.2019.3900
PMC: PMC6902236
OpenAlex: W2993806141
Cited by: 48
References: 25
Citations by year: 2026: 3 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 7 · 2019: 1
FWCI: 4.34
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: JAMA Psychiatry (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Pfizer
AstraZeneca
Patient-Centered Outcomes Research Institute
F. Hoffmann-La Roche
ACADIA Pharmaceuticals
Sage Therapeutics
Avanir Pharmaceuticals
Cerecor
Myriad Genetics
H. Lundbeck A/S
Allergan
National Institute of Mental Health (MH 01697)
Janssen Pharmaceuticals
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
Keywords: major depressive disorder, depression recurrence, antidepressant discontinuation, cognitive behavioral therapy, combination therapy, sustained recovery, relapse prevention, outpatients, chronic depression, treatment discontinuation, number needed to treat
MeSH terms: Antidepressive Agents, Combined Modality Therapy, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Remission Induction, Cognitive Behavioral Therapy, Treatment Outcome, Secondary Prevention

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Prevention of Recurrence After Recovery From a Major Depressive Episode With Antidepressant Medication Alone or in Combination With Cognitive Behavioral Therapy: Phase 2 of a 2-Phase Randomized Clinical Trial

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