Honer William G, Thornton Allen E, Sherwood Megan, MacEwan G William, Ehmann Tom S, Williams Richard, Kopala Lili C, Procyshyn Ric, Barr Alasdair M
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
CNS Drugs. 2007;21(9):699-714. doi: 10.2165/00023210-200721090-00001.
Schizophrenia is one of the most severe and disabling psychiatric disorders. Antipsychotic drugs offer considerable benefits in controlling symptoms and preventing relapse. The strategy for the present review of clinical trials was to ask 'What are the features of schizophrenia and the existing treatments of the illness that have implications for future clinical trials'? Six key facts were identified.First, schizophrenia is genetically 'complex'. Trials may benefit from designs including genetically related illnesses, by focussing on cross-cutting aspects of the phenotype such as psychosis or cognitive dysfunction, and by collecting information on possible moderators and mediators of treatment response.Second, schizophrenia affects multiple neurotransmitter systems. Multiple signalling pathways may need to be considered, with different time courses of response. Outcome measures from clinical trials could be collected at more frequent intervals, particularly in the early phase of response.Third, the clinical features used to define the illness are a mix of symptoms and social-occupational dysfunction, yet treatment response is often defined only by changes in symptoms. Multiple measures of functioning need to be collected at baseline and at the endpoint of trials. Consensus definitions for response, remission, relapse, recovery and recurrence need to be developed.Fourth, schizophrenia is often highly disabling. Linking treatment response in clinical trials to measures of quality-adjusted life-years will allow comparison with other medical illnesses using common metrics.Fifth, the general health and care of individuals with schizophrenia is often poor. 'Complex' interventions, which include, but are not limited to, antipsychotic medications, need to be designed and tested for the problems facing these patients.Finally, large gaps exist between clinical trials, practice guidelines and patterns of practice. Trials need to be designed to investigate widely used approaches such as antipsychotic polypharmacy, where actual practice diverges from evidence-based guidelines.
精神分裂症是最严重且使人致残的精神疾病之一。抗精神病药物在控制症状和预防复发方面有显著益处。本次临床试验综述的策略是提出“精神分裂症的特征以及该疾病现有的治疗方法对未来临床试验有哪些影响？”六个关键事实被确定。首先，精神分裂症在遗传上“复杂”。试验可能会从包括与遗传相关疾病的设计中受益，通过关注表型的交叉方面，如精神病或认知功能障碍，并收集关于治疗反应可能的调节因素和中介因素的信息。其次，精神分裂症影响多个神经递质系统。可能需要考虑多个信号通路，且反应的时间进程不同。临床试验的结果测量可以更频繁地收集，特别是在反应的早期阶段。第三，用于定义该疾病的临床特征是症状和社会职业功能障碍的混合，但治疗反应通常仅由症状变化来定义。在试验的基线和终点需要收集多种功能测量指标。需要制定关于反应、缓解、复发、康复和再发的共识定义。第四，精神分裂症通常具有高度致残性。将临床试验中的治疗反应与质量调整生命年的测量指标联系起来，将允许使用共同的指标与其他医学疾病进行比较。第五，精神分裂症患者的总体健康和护理往往较差。需要针对这些患者面临的问题设计并测试“复杂”干预措施，这些措施包括但不限于抗精神病药物。最后，临床试验、实践指南和实践模式之间存在很大差距。试验需要设计来研究广泛使用的方法，如抗精神病药物联合使用，因为实际实践与循证指南存在差异。
