Roy Chengappa Kn, Kupfer David J, Parepally Haranath, John Vineeth, Basu Ranita, Buttenfield Joan, Schlicht Patricia, Houck Patricia, Brar Jaspreet S, Gershon Samuel
Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, and Mayview State Hospital, Pittsburgh, PA, USA.
Bipolar Disord. 2007 Sep;9(6):609-17. doi: 10.1111/j.1399-5618.2007.00506.x.
This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT).
A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100-400 mg/day) or placebo. Patients who had achieved a > or =20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values.
Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo-treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to > or =10% from baseline), and no significant differences between the treatments on worsening of total Montgomery-Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate].
This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI.
本初步研究评估了辅助使用托吡酯与安慰剂相比，在治疗双相型分裂情感障碍（SAD - BT）患者中的疗效和安全性。
选取48例成年患者，根据《精神障碍诊断与统计手册》第四版修订版（DSM - IV - TR）诊断为SAD - BT（经DSM - IV轴I障碍结构化临床访谈患者版支持），按2:1比例（倾向于托吡酯组）随机分配，接受为期8周的双盲治疗，分别使用托吡酯（100 - 400毫克/天）或安慰剂。阳性和阴性症状量表（PANSS）总分较基线下降≥20%的患者有机会继续接受额外8周的双盲治疗。研究药物剂量与早期8周研究期保持不变。在研究期结束时，研究药物在2周内逐渐减量并停药。主要疗效在8周时通过随机分组患者意向性治疗人群中两组PANSS总分的平均变化进行评估。还评估了多项次要指标。安全性分析包括监测不良事件、生命体征、心电图（ECG）和实验室值。
尽管两种治疗均降低了各种精神病理学评定量表的评分，但辅助使用托吡酯治疗（近275毫克/天）在主要结局指标（PANSS量表）或任何次要结局指标上相对于安慰剂并未显示出更高的疗效。托吡酯治疗的患者体重减轻显著多于安慰剂治疗的患者，导致体重指数（BMI）显著降低。相对于辅助使用安慰剂，托吡酯治疗的患者出现感觉异常、镇静、找词困难、嗜睡和健忘的发生率更高，但这些差异无统计学意义。心电图或实验室结果均无临床显著异常。研究中未出现严重不良事件。此外，PANSS总分未恶化（较基线升高≥10%），且在蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）总分恶化方面，两种治疗之间无显著差异[安慰剂组为1/13（7.7%）；托吡酯组为1/25（4.0%）]。
本初步研究不支持辅助使用托吡酯治疗SAD - BT患者的临床疗效。本研究中未出现重大安全性或耐受性问题。与其他研究结果一致，托吡酯治疗的患者确实体重减轻更多且BMI降低。
