Remington Gary, Saha Amitabha, Chong Siow-Ann, Shammi Chekkera
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
CNS Drugs. 2005;19(10):843-72. doi: 10.2165/00023210-200519100-00004.
The introduction of antipsychotics in the 1950s revolutionised the treatment of schizophrenia, but it soon became apparent that a substantial number of patients demonstrated a suboptimal response to these antipsychotics. Clozapine proved to be beneficial in patients whose symptoms were treatment resistant, but it too had limitations, with as many as 40-70% of those treated with clozapine demonstrating inadequate response to this drug as well. The availability of other 'atypical' antipsychotics offers options, but clozapine appears to remain the most effective option in treatment-resistant schizophrenia. This, of course, raises the question of what to do when clozapine is only partially effective. To address the issue of treatment in patients who have demonstrated a suboptimal response to clozapine, efforts have focused on a variety of augmentation strategies, including numerous medications and electroconvulsive therapy. The current body of evidence consists largely of data from smaller open trials and case series/reports, although data from a limited number of controlled studies are now available. Not surprisingly, the evidence drawn from the former is more supportive of augmentation strategies, although the controlled trials are not without positive findings. The available information is certainly not so overwhelming as to endorse any single augmentation approach. Indeed, it argues for more controlled data and cautions us regarding the cost-benefit ratio in adopting this strategy. Over and above the added adverse effects of another treatment, there is evidence to indicate that actual clinical worsening can occur. Without compelling evidence, clinicians must resort to guiding principles. The potential benefits of augmentation cannot be ruled out, but it should be approached with caution and in a systematic fashion. Factors compromising clozapine response should first be ruled out, and any augmentation trials should be guided by existing evidence and a treatment plan that incorporates a clear understanding of target symptoms. A means of evaluating outcome effectively needs to be in place, and the trial should be circumscribed to prevent needless polypharmacy. A priori, an endpoint needs to be established and the trial discontinued unless results firmly support added benefits.
20世纪50年代抗精神病药物的引入彻底改变了精神分裂症的治疗方式，但很快就发现，相当多的患者对这些抗精神病药物的反应并不理想。事实证明，氯氮平对那些症状具有治疗抵抗性的患者有益，但它也有局限性，接受氯氮平治疗的患者中多达40%-70%对这种药物反应不佳。其他“非典型”抗精神病药物的出现提供了更多选择，但氯氮平似乎仍然是治疗抵抗性精神分裂症最有效的选择。当然，这就引出了一个问题：当氯氮平仅部分有效时该怎么办。为了解决对氯氮平反应欠佳患者的治疗问题，人们致力于多种增效策略，包括使用多种药物和采用电休克疗法。目前的证据主要来自较小规模的开放试验以及病例系列/报告的数据，不过现在也有一些来自有限数量对照研究的数据。不出所料，前者得出的证据更支持增效策略，尽管对照试验也有一些积极的发现。现有的信息肯定不足以支持任何单一的增效方法。实际上，这表明需要更多的对照数据，并提醒我们在采用这种策略时要考虑成本效益比。除了另一种治疗带来的额外不良反应外，有证据表明实际临床病情可能会恶化。在没有确凿证据的情况下，临床医生必须遵循指导原则。增效的潜在益处不能排除，但应谨慎并系统地采用。首先应排除影响氯氮平反应的因素，任何增效试验都应以现有证据和对目标症状有清晰理解的治疗计划为指导。需要有一种有效评估结果的方法，并且试验应加以限制以防止不必要的联合用药。事先需要确定一个终点，除非结果明确支持额外的益处，否则应停止试验。
