Antipsychotic Withdrawal - Individual Patient Data Analysis of the Placebo Groups in Randomized Controlled Trials
Final Report Abstract
Discontinuation of antipsychotics may be associated with the occurrence of adverse events and an increased risk of relapse. However, there is a lack of evidence concerning the risk and predictors of adverse events and relapse. The aim of this study was to assess the occurrence of adverse events and relapse following antipsychotic discontinuation. For the analyses of individual participant data, we searched the database of the Yale Open Data Access Project for randomised placebo-controlled trials of antipsychotics with participants with schizophrenia, schizoaffective disorder, or bipolar disorder. The occurrence of adverse events after antipsychotic discontinuation was assessed with metaanalyses. The risk of relapse was analysed with machine learning techniques. The results showed evidence of an increased risk of somatic and psychiatric adverse events after antipsychotic discontinuation. It is of clinical relevance that a longer duration of treatment before discontinuation was associated with a higher probability of somatic adverse events after antipsychotic discontinuation, while tapered discontinuation (compared with abrupt discontinuation) was associated with a lower probability of somatic adverse events after antipsychotic discontinuation. The emergence of distinct adverse events might be partly explained by the receptor affinities of the discontinued antipsychotic (e.g., cholinergic adverse events such as nausea might increase after discontinuation of anticholinergic antipsychotics). We identified general prognostic factors of psychotic relapse after antipsychotic discontinuation that include clinical, social (e.g., social functioning), and behavioural (e.g., substance use) variables indicating the multifactorial aetiology of psychotic relapse. Predictors of increased risk specifically after antipsychotic discontinuation were abrupt discontinuation of higher dosages of oral antipsychotics, especially for individuals with recurring hospitalisations, higher severity of the clinical global impression, and increased prolactin concentrations (prolactin may be increased due to high dopamine receptor occupancy as well as stress before antipsychotic discontinuation). The occurrence of adverse events and relapse after antipsychotic discontinuation has important clinical implications for treatment safety and requires consideration in treatment planning and design of clinical trials. The findings from this study support the importance of informing about safe tapering strategies in evidence-based and consensus-based guidelines to reduce the risk of adverse events and relapse. It appears advisable to differentiate between prognostic factors and interventionspecific predictors of illness trajectories in clinical practice, treatment guidelines, and future research of psychotic disorders.
Publications
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Symposium. Congress of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), Topic: Pharmakotherapy, Title: Absetzen von psychiatrischen Medikamenten. 2019.
Gutwinski, S.; Hasan, A.; Remi, J.; Henssler, J. & Brandt, L.
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Symposium. Congress of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), Topic: Psychotic Disorders, Title: Absetzen von psychiatrischen Medikamenten. 2020.
Gutwinski, S.; Hasan, A.; Henssler, J. & Brandt, L.
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Symposium. Congress of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), Topic: Pharmakotherapy, Title: Absetzen und Reduktion von psychiatrischen Medikamenten. 2021.
Gutwinski, S.; Hasan, A.; Henssler, J. & Brandt, L.
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Adverse events after antipsychotic discontinuation: an individual participant data meta-analysis. The Lancet Psychiatry, 9(3), 232-242.
Brandt, Lasse; Schneider-Thoma, Johannes; Siafis, Spyridon; Efthimiou, Orestis; Bermpohl, Felix; Loncar, Luka; Neumann, Konrad; Hasan, Alkomiet; Heinz, Andreas; Leucht, Stefan & Gutwinski, Stefan
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Symposium. Congress of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), Topic: Pharmakotherapy, Title: Absetzen und Reduktion von psychiatrischen Medikamenten. 2022.
Gutwinski, S.; Hasan, A.; Henssler, J. & Brandt, L.
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Workshop. Congress of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), Topic: WS-148, Title: Reduktion und Absetzen von Psychopharmaka: Antidepressiva und Antipsychotika. 2022
Walter, H.; Henssler, J. & Brandt, L.
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Predicting psychotic relapse following randomised discontinuation of paliperidone in individuals with schizophrenia or schizoaffective disorder: an individual participant data analysis. The Lancet Psychiatry, 10(3), 184-196.
Brandt, Lasse; Ritter, Kerstin; Schneider-Thoma, Johannes; Siafis, Spyridon; Montag, Christiane; Ayrilmaz, Hakan; Bermpohl, Felix; Hasan, Alkomiet; Heinz, Andreas; Leucht, Stefan; Gutwinski, Stefan & Stuke, Heiner
