Relapse Prevention in First-Episode Schizophrenia—Maintenance vs Intermittent Drug Treatment With Prodrome-Based Early Intervention: Results of a Randomized Controlled Trial Within the German Research Network on Schizophrenia
Abstract
OBJECTIVE: After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. METHOD: A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). RESULTS: Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. CONCLUSIONS: Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00159120.
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It is likely that discontinuation studies employing linear dose reductions will be more likely to induce withdrawal reactions (including, potentially, withdrawal psychosis) because reductions in D2 antagonism become increasingly large, causing greater likelihood of dopaminergic rebound.
“It is, therefore, likely that discontinuation studies employing linear dose reductions,74,83,84,86,87 as recommended in some older guidelines,94 will be more likely to induce withdrawal reactions (including, potentially, withdrawal psychosis) because reductions in D2 antagonism become increasingly large, causing greater likelihood of dopaminergic rebound.”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [87]
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Kann eine Langzeitbehandlung mit Antipsychotika zu strukturellen Hirnschäden führen? Kontra
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Classical Somatic Treatments: Pharmacotherapy and ECT
Sommer, I. E., & Blom, J. D. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0959-5_24 · Cited by 1 · see citing works
SCHIZOPHRÉNIE ET AUTRES TROUBLES PSYCHOTIQUES À DÉBUT PRÉCOCE
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Schizophrenia and other psychotic disorders of early onset
Starling, J., & Feijo, I. (2013) · doi:10.13140/2.1.1881.1846 · Cited by 1 · see citing works
Risks of Intermittent Antipsychotic Treatment in Schizophrenia
Suzuki, T., Nomura, K., & Watanabe, K. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10lr06452yel
Frontale Hirnvolumen- minderung durch Antipsychotika?
Greifswald, E.-M.-A.-U. (2015)
Early schizophrenia: skilful management of medication
Cookson, J. (2015) · BJPsych Advances · doi:10.1192/apt.bp.114.013359
“A similar conclusion was reached by Gaebel et al (2011) (Table 3).”
Pharmakotherapie und andere somatische Behandlungsverfahren (Modul 4a)
Gäebel, W., Hasan, A., & Falkai, P. (2019) · Springer eBooks · doi:10.1007/978-3-662-59380-6_5
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Evolving Concepts for the Assessment and Treatment of Schizophrenia
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Recidivas em esquizofrenia: um estudo brasileiro
Ribeiro, L. D. C., Arruda, F. S., Maciel, G. M., & Bulhões, G. P. (2026) · Jornal Brasileiro de Psiquiatria · doi:10.1590/0047-2085-2025-0040
- Authors
- Gaebel, W., Riesbeck, M., Wölwer, W., Klimke, A., Eickhoff, M., von Wilmsdorff, M., Lemke, M., Heuser, I., Maier, W., Huff, W., Schmitt, A., Sauer, H., Riedel, M., Klingberg, S., Köpcke, W., Ohmann, C., Möller, H.-J., & German Study Group on First-Episode Schizophrenia
- ORCID
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2010-06-29
- Volume
- 72
- Issue
- 02
- Pages
- 205-218
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2032982738
- Cited by
- 92
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 1 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 16 · 2012: 9
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- GRO (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 › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- first-episode schizophrenia, relapse prevention, decision-making algorithm, extrapyramidal symptoms, quality of life, functional decline, treatment refusal
- MeSH terms
- Acute Disease, Adult, Combined Modality Therapy, Double-Blind Method, Female, Germany, Haloperidol, Humans, Long-Term Care, Male, Middle Aged, Patient Education as Topic, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Schizotypal Personality Disorder, Antipsychotic Agents, Cognitive Behavioral Therapy, Risperidone, Secondary Prevention
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