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Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial
Abstract
IMPORTANCE: Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. OBJECTIVE: To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. DESIGN: Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. SETTING: One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. INTERVENTION: After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. MAIN OUTCOMES AND MEASURES: Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. RESULTS: The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. CONCLUSIONS AND RELEVANCE: Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16228411.
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“That is, relapses are not distributed evenly across time but tend to occur predominantly around the point of drug cessation.”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [57]
In the citing paper
“It appears that relapse rates are raised in the discontinuation group for 1–3 years following a switch to placebo, before converging with relapse rates of medicated patients thereafter.3,56–59”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [57]
In the citing paper
“one found 43% of the original cohort of patients relapsed in the first year, 21.5% in the second year, and just 3.7% a year in each of the 5 years following57,61”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [57]
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Twumasi, R., Gronemann, F. H., Hjorthøj, C. R., Howes, O. D., Lange, M., Nordentoft, M., & Osler, M. (2026) · Psychological Medicine · doi:10.1017/s0033291726104693 · Cited by 2
Chopra, S., Holmes, A., Segal, A., Zhang, X.-H., Francey, S. M., O'Donoghue, B. N., Cropley, V., Nelson, B., Graham, J., Baldwin, L., et al. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.06.028 · Cited by 5
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Metadata
- Authors
- Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Wunderink, Lex
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2013-09-01
- Volume
- 70
- Issue
- 9
- Pages
- 913
- ISSN
- 2168-622X (ISSN-L)
- OpenAlex
- W2125616168
- Cited by
- 567
- References
- 24
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 31 · 2023: 39 · 2022: 37 · 2021: 47 · 2020: 42 · 2019: 71 · 2018: 59 · 2017: 43 · 2016: 65 · 2015: 42 · 2014: 36 · 2013: 8
- FWCI
- 35.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Psychology › Clinical Psychology › Psychiatric care and mental health services
- Keywords
- first-episode psychosis, remission, antipsychotic dose reduction, antipsychotic discontinuation, long-term antipsychotic treatment, long-term recovery, functional remission, symptom remission, relapse
- MeSH terms
- Adult, Female, Follow-Up Studies, Humans, Long-Term Care, Male, Psychotic Disorders, Recurrence, Remission Induction, Antipsychotic Agents, Treatment Outcome, Age of Onset, Young Adult, Maintenance Chemotherapy
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