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：所有治疗指南一致推荐抗精神病药物治疗以预防精神分裂症复发。这种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。在这种情况下，必须考虑到，在总共65项评估精神分裂症复发预防的临床试验中，只有2项（n=54）研究了缓解期超过3年的参与者。由于证据不足，关于抗精神病药预防复发的最佳时间长短的建议存在很大分歧，有些人放弃了建议时间框架（例如NICE指南）。这种缺乏证据的情况应以目前的项目建议来结束。目的：评价缓解期至少3年的精神分裂症患者是否可以停用抗精神病药物或继续使用抗精神病药物预防复发。研究设计：本项目为单中心、随机、单（非）盲、平行、纵向先导试验，纳入25例精神分裂症（精神分裂症或分裂情感性障碍）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（即没有精神病住院治疗）。患者将被随机分为两组：干预组停止抗精神病药物治疗，对照组继续进行药物治疗。每位参与者的最长有效试验持续时间为26周。复发被定义为主要结局。此外，次要结局包括精神疾病再住院、精神疾病评定量表的改变、生活质量、工作能力、个人和社会功能、依从性、退出、运动障碍和特定不良反应的发生。统计分析包括比较两组患者的复发率（Fisher’s Exact Test）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。相关性和意义：本项目提案将首次采用高质量的方法评估抗精神病药物预防复发应该持续多长时间，以及患者受到足够保护的时间，以便停药似乎是合适的。由于在抗精神病药物治疗过程中大多发生不可逆的不良反应，这一研究问题具有很高的临床相关性，本研究将在精神分裂症及相关疾病的精神药物治疗方面取得重要成果。

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the present project proposal.Aim: Evaluation, if the pharmacological relapse-prevention with antipsychotics can be withdrawn for schizophrenic patients who are in remission for at least 3 years or should be further continued.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 The patients will be randomised in two study arms: The pharmacotherapy with antipsychotics will be withdrawn in the intervention group and continued in the control group.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