Yamanouchi Yoshio, Sukegawa Tsuruhei, Inagaki Ataru, Inada Toshiya, Yoshio Takashi, Yoshimura Reiji, Iwata Nakao
Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
Int J Neuropsychopharmacol. 2014 Dec 11;18(5):pyu016. doi: 10.1093/ijnp/pyu016.
Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients.
In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient's treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model.
Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 - 0.085, P = .24-.97), despite high statistical power (1-β = 0.48-0.97). The findings are limited by the nonuniformity of the participants' treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group.
Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our "slowly" method is well tolerated. We hope that this approach will result in therapeutic improvements.
现有临床证据无法证明用于精神分裂症治疗的联合用药是合理的。我们评估了一种治疗减量方法，该方法可同时减少给患者同时开具的抗精神病药物的剂量和数量。
在一项由日本厚生劳动省资助的“抗精神病药物联合用药及高剂量处方的安全调整”项目的随机开放研究中，我们评估了一种药物减量方法，该方法包括对163例精神分裂症患者进行为期12周或24周的剂量减少干预。通过将剂量减少0至50氯丙嗪等效剂量，每周从每位患者的治疗方案中停用一种抗精神病药物。使用双向重复测量混合线性模型分析与健康相关的生活质量指标、临床症状和副作用风险的数据。
尽管抗精神病药物剂量降低了23%，但在剂量减少组和观察组之间未观察到结果差异（效应大小=0.001 - 0.085，P = 0.24 - 0.97），尽管统计功效较高（1-β = 0.48 - 0.97）。研究结果受到参与者治疗史、持续时间和剂量减少量不一致的限制。与观察组相比，剂量减少方案组的患者在精神病症状或不良事件方面没有差异。
重要的是，我们研究中的低退出率（6.9%的参与者因患者因素退出，所有次要原因导致的退出率为23.8%）表明我们的“缓慢”方法耐受性良好。我们希望这种方法能带来治疗上的改善。
