Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial
Open accessAbstract
Background Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence.Methods In this single-blind, multicentre, parallel, three-group, randomised controlled trial, individuals recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (10:10:8) to PCT and antidepressants, antidepressants alone, or PCT with tapering of antidepressants, using computer-generated randomised allocation stratified for number of previous depressive episodes and type of care. Eligible participants had previously experienced at least two depressive episodes and were in remission or recovery on antidepressants, which they had been receiving for at least the past 6 months. Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage. The primary outcome was time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, assessed four times in 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked. This trial is registered with the Netherlands Trial Register, number NTR1907.Findings Between July 14, 2009, and April 30, 2015, 2486 participants were assessed for eligibility and 289 were randomly assigned to PCT and antidepressant (n=104), antidepressant alone (n=100), or PCT with tapering of antidepressant (n=85). The overall log-rank test was significant (p=0·014). Antidepressants alone were not superior to PCT while tapering off antidepressants in terms of the risk of relapse or recurrence (hazard ratio [HR] 0·86, 95% CI 0·56-1·32; p=0·502). Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction compared with antidepressants alone (0·59, 0·38-0·94; p=0·026). There were two suicide attempts (one in the antidepressants alone group and one in the PCT with tapering of antidepressants group) and one death (in the PCT and antidepressants group) not related to the interventions during the 24 months' follow-up.Interpretation Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding PCT to antidepressant treatment after recovery is superior to antidepressants alone. PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery.Funding The Netherlands Organisation for Health Research and Development.
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In Bockting 2018, 19% (8/43) of participants in the discontinuation group reduced their dose by at least 50%.
“16 of 85 (split 8/43) (19%) were able to reduce the dose by a minimum of 50%.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
In the Results baseline table (page unavailable), 16/85 (19%) refers to participants receiving current psychological or psychotherapeutic treatment, not to antidepressant dose reduction. The Statistical analysis section defines a 50% dose reduction for a per-protocol analysis, but does not report 8/43 or 16/85 as achieving it. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn Bockting 2018, 40% (17/43) of participants in the discontinuation with PCT group discontinued their antidepressant after six months.
“Bockting 2018 reported that 34 of 85 (split to allow multiple-arm comparisons: 17/43) (40%) participants in the discontinuation with PCT group followed the discontinuation advice and discontinued their antidepressant a er six months”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
The Results (page unavailable) identify 85 participants assigned to PCT while tapering antidepressants, supporting the group size. They report that 30 of 50 participants still in the study after six months adhered to the antidepressant protocol, but do not report that 34 of 85 discontinued antidepressants or establish the citing paper’s split figure of 17/43. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn Bockting 2018, 38 of 100 participants in the control group adhered to antidepressant treatment (maintaining at least 20 mg) after six months.
“In all, 38 of 100 participants in the control group adhered to antidepressant treatment (maintaining ≥ 20 mg antidepressant) a er six months.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
The Results report that 38 of 66 participants still in the antidepressants-alone group after six months adhered to the antidepressant protocol; 100 were originally assigned to that group. The Procedures specify a maintenance dose of at least 20 mg fluoxetine equivalent, but the claim uses the original group size as the adherence denominator rather than the 66 assessed at six months. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThere was no difference in risk of relapse between participants discontinuing antidepressants with support from MBCT or PCT compared to those continuing antidepressants (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies).
“There was no difference in risk of relapse (as defined by study authors) between participants discontinuing antidepressants with support from MBCT or PCT compared to those continuing antidepressants (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
The Results report no significant difference in recurrence between PCT with antidepressant tapering and continued antidepressants (HR 0.86, 95% CI 0.56–1.32). The Discussion also describes three earlier MBCT trials as finding no clinically meaningful difference from maintenance medication. The paper does not report the claimed pooled HR of 0.89 (95% CI 0.66–1.19) for 690 participants across three MBCT-or-PCT studies. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBockting 2018 (n = 185; split 143) reported two suicide attempts (one in the PCT with tapering group and one in the antidepressants only group) and no deaths in both groups.
“They reported two suicide attempts (one in the PCT with tapering of antidepressants group, and one in the antidepressants only group).Study authors reported no indication that these were Cochrane Database of Systematic Reviews related to the interventions.They reported no deaths in both groups.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Bockting 2018 (n = 185; split 143) reported two suicide attempts (one in the discontinuation with PCT group and one in the continuation group) during the 104-week follow-up, and study authors reported these events were not related to the interventions.
“Bockting 2018 (n = 185; split 143) reported two suicide attempts (one in the discontinuation with PCT group, and one in the continuation group) during the 104-week follow-up.Study authors reported that these events were not related to the interventions.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn other trials in Canada and the Netherlands, some principles of WBT were used in addition to standard cognitive therapy.
“In other trials that took place in Canada 77 and the Netherlands 78 , some principles of WBT were used in addition to standard cognitive therapy.”
From The pursuit of euthymia (2020) · cites this paper as [78]
The Procedures section describes a Dutch trial of preventive cognitive therapy that included work on positive emotions and memories alongside evaluation of dysfunctional attitudes. The paper does not identify these components as principles of well-being therapy (WBT) or say that WBT principles were added to standard cognitive therapy. No page number is available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredBockting 2018 reported one suicide attempt in the tapering group and one death in the continuation with PCT group.
“Bockting 2018 (n = 146) recorded serious adverse events and reported one suicide attempt in the tapering group; one participant in the continuation with PCT group died.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
A four-week time frame is not feasible for many long-term users of antidepressants.
“suggesting that a time frame of four weeks is not feasible for many long-term users of antidepressants (Bockting 2018).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
One included study found that most participants, 60%, tapered antidepressants over six months.
“However, one included study found that most participants (60%) tapered antidepressants over six months”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
A possible reason this review did not confirm the 60-week MBCT effect is that it pooled studies with their original longer durations and included a later published study.
“possibly because we pooled studies with their original longer duration (e.g.longer than 60 weeks) (as defined in our protocol) and included a later published study (Bockting 2018).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
In Bockting 2018, 17/42 (40%) in discontinuation group discontinued antidepressant after six months and 8/42 (19%) reduced dose by at least 50%.
“This study reported that 17 of 42 (40%) participants in the discontinuation group discontinued the antidepressant a er six months and 8 of 42 participants (19%) were able to reduce the dose by a minimum of 50%.”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
The Results report six-month protocol adherence as 30 of 50 participants in the PCT-with-tapering group, not the claimed discontinuation and dose-reduction figures. The Statistical analysis section uses a 50% dose reduction within six months as a per-protocol criterion, but our copy does not report 17/42 discontinuing or 8/42 reducing their dose; searches for both fractions and percentages found no matching passage. No page numbers were available in the indexed passages. (LLM, conf=0.75)
Experimental — accuracy not yet measuredBockting 2018 reported mean QALYs over 24 months of 1.59 (range 0.64 to 1.94) for the discontinuation with PCT group (n=42) and 1.62 (range 0.95 to 1.95) for the continuation and PCT group (n=104).
“Mean QALYs over 24 months were 1.59 (range 0.64 to 1.94) for the discontinuation with PCT group (n = 42) and 1.62 (range 0.95 to 1.95) for the continuation and PCT group (n = 104).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Bockting 2018
The Outcomes section (page unavailable) says cost-effectiveness results would be reported elsewhere; our copy does not report QALYs. The Results identify a 24-month follow-up and 104 participants allocated to PCT plus maintenance antidepressants, but do not give the claimed QALY means, ranges, or discontinuation-group sample of 42 (searched: QALYs, quality-adjusted life years, and the stated values). (LLM, conf=0.78)
Experimental — accuracy not yet measured
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- Authors
- Bockting, C. L. H., Klein, N. S., Elgersma, H. J., van Rijsbergen, G. D., Slofstra, C., Ormel, J., Buskens, E., Dekker, J., de Jong, P. J., Nolen, W. A., Schene, A. H., Hollon, S. D., & Burger, H.
- Affiliations
- University of Groningen (NL)
- Lentis (NL)
- University Medical Center Groningen (NL)
- Arkin (NL)
- Radboud University Nijmegen (NL)
- Vanderbilt University (US)
- Corresponding author
- Bockting, Claudi L H
- ORCID
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 5
- Issue
- 5
- Pages
- 401-410
- ISSN
- 2215-0366 (ISSN-L)
- OpenAlex
- W2795882974
- Semantic Scholar
- 1cd6dba1a2b098d2f7050a3bdffe9a9c9e148cfd
- Cited by
- 130
- References
- 32
- Citations by year
- 2026: 22 · 2025: 10 · 2024: 10 · 2023: 17 · 2022: 12 · 2021: 11 · 2020: 18 · 2019: 17 · 2018: 12 · 2017: 1
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- ZonMw (171002401)
- 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 › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- antidepressant tapering, major depressive disorder, depression relapse, depression recurrence, relapse prevention, remission, combination therapy, antidepressant side effects, health care utilization, general practitioners, primary care, secondary mental health care
- MeSH terms
- Antidepressive Agents, Combined Modality Therapy, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Netherlands, Psychotherapy, Recurrence, Cognitive Behavioral Therapy, Single-Blind Method, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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