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

背景：所有治疗指南都一致推荐使用抗精神病药物进行药物治疗，以防止精神分裂症障碍患者的精神病复发。这一药物治疗策略的有效性可以在我们工作组进行的荟萃分析中得到验证。在这方面，必须考虑的是，在评估精神分裂症复发预防的总共65项临床试验中，只有2项(n=54)检查了缓解期超过3年的参与者。由于证据不足，关于抗精神病药物复发的最佳持续时间的建议存在很大分歧，一些人不建议时间框架(例如，NICE指南)。这一证据的缺乏应该随着本项目的提出而结束。目的：评估对于缓解期至少3年或应该继续进行的精神分裂症患者，是否可以停止使用抗精神病药物进行药物复发预防。研究设计：本项目包含一项单中心、随机、单(评价者)盲、平行、纵向先导试验，包括25名精神分裂症(精神分裂症或分裂情感障碍)患者。参与者必须在稳定的抗精神病药物治疗下缓解至少3年(即没有精神病住院)。患者将被随机分成两组：干预组停用抗精神病药物，对照组继续用药。每个参与者的最长有效试用期为26周。复发被定义为主要结果。统计分析包括两个研究组的复发率(菲舍尔精确检验)和复发时间(Kaplan-Meier-Curve，Logrank-Test)、Cox回归、协方差分析(ANCOVA)和描述性统计。相关性和影响：本项目提案将首次采用高质量的方法，评估抗精神病药物复发预防应该持续多久，以及患者得到足够保护的时间，以便停药似乎是合适的。由于在抗精神病药物治疗过程中发生的不良反应大多是不可逆转的，这一研究问题具有很高的临床意义，本研究将对精神分裂症及相关障碍的精神药物治疗产生重要的结果。

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with the present project proposal.Aim: Evaluation, if the pharmacological relapse-prevention with antipsychotics can be withdrawn for schizophrenic patients who are in remission for at least 3 years or should be further continued.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 The patients will be randomised in two study arms: The pharmacotherapy with antipsychotics will be withdrawn in the intervention group and continued in the control group.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.