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

背景资料：所有的治疗指南都一致推荐使用抗精神病药物进行药物治疗，以防止精神分裂症的精神病复发。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，只有2（n=54），总共65个临床试验评估复发预防精神分裂症研究参与者谁是在缓解超过3年。由于证据不足，关于抗精神病药物预防复发的最佳时间的建议存在很大分歧，有些人不建议时间范围（例如NICE指南）。这种缺乏证据应关闭与本项目proposal.Aim：评价，如果药物复发预防与抗精神病药物可以撤回精神分裂症患者谁是在缓解至少3年或应进一步继续。研究设计：本项目包括一个单中心、随机、单盲、平行、纵向的先导试验，其中包括25例精神分裂症（精神分裂症或情感性精神障碍）患者。受试者必须在稳定的抗精神病药物治疗下缓解至少3年（即无精神病住院）。患者将随机分为两个研究组：干预组将停止抗精神病药物治疗，对照组继续。每例受试者的最长活性试验持续时间为26周。复发被定义为主要结局。次要结局包括精神病再住院、精神病评定量表的变化、生活质量、工作能力、个人和社会功能、依从性、脱落、运动障碍和特定不良反应的发生。统计分析包含两个研究组复发率的比较（Fisher精确检验）以及复发时间（Kaplan-Meier曲线，对数秩检验）、考克斯回归、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持续多久，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数不可逆的不良反应的发生，本研究的问题在临床上具有高度相关性，本研究将产生关于精神分裂症和相关疾病的精神药物治疗的重要结果。

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the present project proposal.Aim: Evaluation, if the pharmacological relapse-prevention with antipsychotics can be withdrawn for schizophrenic patients who are in remission for at least 3 years or should be further continued.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 The patients will be randomised in two study arms: The pharmacotherapy with antipsychotics will be withdrawn in the intervention group and continued in the control group.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