Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada
J Clin Psychiatry. 2011 Aug;72(8):1042-8. doi: 10.4088/JCP.09m05866yel. Epub 2010 Sep 7.
In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, "extended" dosing, which allows for intermittent but regular dosing.
We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV-defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007.
Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group.
These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks.
clinicaltrials.gov Identifier: NCT00431574.
在治疗精神分裂症方面，目前所有的口服抗精神病药物都至少需要每天服用一次，并强烈鼓励严格遵守，以最大限度地降低复发的风险。基于对抗精神病药物大脑动力学的更好理解，我们提出了这种方法的一种变体，即“延长”给药，允许间歇性但定期给药。
我们进行了一项随机、双盲、安慰剂对照试验，评估了 35 名符合 DSM-IV 定义的精神分裂症患者，他们已经稳定接受抗精神病药物治疗。在 6 个月的时间里，18 名受试者按常规（每天）服用药物，而 17 名受试者每隔一天服用抗精神病药物（延长）。评估结果包括评估症状的临床量表（简明精神病评定量表[主要评估指标]、卡尔加里抑郁量表）、疾病严重程度（临床总体印象-疾病严重程度量表）和复发（即住院）率。还评估了副作用，包括运动障碍（巴恩斯静坐不能量表、辛普森-安格斯量表、异常不自主运动量表）和体重。该研究于 2003 年 2 月至 2007 年 7 月进行。
延长给药组的个体没有更高的症状恶化、复发或住院风险；实际上，接受常规给药的个体发生了更多的住院治疗。与此同时，延长给药组的副作用也没有明显减少的迹象。
这些结果挑战了长期以来的教条，即稳定的精神分裂症患者必须每天服用口服抗精神病药物。需要进一步进行更大样本的研究来复制这些发现，并阐明假设的临床优势是否能够建立并确定其超过潜在风险。
clinicaltrials.gov 标识符：NCT00431574。
