Evaluation of the necessity of a pharmacological treatment with antipsychotics for the prevention of relapse in long-term stabilized schizophrenic patients: a randomized, single-blind, longitudinal trial

• Applicant: Professor Dr. Stefan Leucht, since 10/2014
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228632533

Background: All treatment guidelines recommend consistently a pharmacotherapy with antipsychotic drugs to prevent a psychotic relapse in schizophrenic disorders. The efficacy of this pharmacological treatment strategy could be verified in a meta-anaysis conducted by our work-group. In this context, it must be considered that only 2 (n=54) of altogether 65 clinical trials evaluating relapse-prevention in schizophrenia examined participants who were in remission for longer than 3 years. Because of this deficient evidence the recommendations diverge regarding the optimum length of an antipsychotic relapse-prevention enormously und some abstain from advising a time frame (e.g. the NICE guidelines). This lack of evidence should be closed with the present project proposal.Aim: Evaluation, if the pharmacological relapse-prevention with antipsychotics can be withdrawn for schizophrenic patients who are in remission for at least 3 years or should be further continued. Study design: The present project contains a mono-center, randomized, single (rater-) blinded, parallel, longitudinal pilot trial, which includes 25 patients with a schizophrenic disorder (schizophrenia or schizoaffective disorder). The participants have to be in remission for at least 3 years (i.e. no psychiatric hospitalisation) under a stable antipsychotic medication. The patients will be randomised in two study arms: The pharmacotherapy with antipsychotics will be withdrawn in the intervention group and continued in the control group. The maximum active trial duration is 26 weeks for every participant. Relapse is defined as primary outcome. Among other, secondary outcomes are psychiatric rehospitalisation, changes in psychiatric rating scales, quality of life, ability to work, personal and social functioning, adherence, drop-outs, movement disorders, and the occurrence of specific adverse effects.The statistical analysis contains a comparison of the relapse rates in both study groups (Fisher`s Exact Test) as well as the time to relapse (Kaplan-Meier-Curve, Logrank-Test), Cox regression, analyses of covariance (ANCOVA) and descriptive statistics. Relevance and implications: The present project proposal will evaluate for the first time employing high-quality methodology, how long an antipsychotic relapse-prevention should be continued and to which time a patient is protected enough, so that a withdrawal of the medication seems appropriate. Due to the occurrence of mostly irreversible adverse effects during the antipsychotic medication this research question is clinically highly relevant and the present study will yield important results regarding the psychopharmacotherapy of schizophrenia and related disorders.

• DFG Programme: Research Grants
• Participating Institution: Klinikum der Technischen Universität München (TUM Klinikum); Institut für KI und Informatik in der Medizin; Südbayerisches Fernstudienzentrum an der Technischen Universität München
• Participating Person: Dr. Stephan Heres
• Ehemaliger Antragsteller: Dr. Markus Dold, until 10/2014