McIntyre Roger S, McElroy Susan L, Eudicone James M, Forbes Robert A, Carlson Berit X, Baker Ross A
Department of Psychiatry and Pharmacology, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada (Dr McIntyre); Linder Center of Hope, Mason, Ohio, and University of Cincinnati College of Medicine, Cincinnati, Ohio (Dr McElroy); Bristol-Myers Squibb, Plainsboro, New Jersey (Mr Eudicone and Dr Carlson); and Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey (Drs Forbes and Baker).
Prim Care Companion CNS Disord. 2011;13(6). doi: 10.4088/PCC.11m01182.
Metabolic risk factors, termed metabolic syndrome, which include obesity, diabetes, dyslipidemia, and hypertension, are more common in patients with bipolar disorder than in the general population. Moreover, medications used to treat bipolar disorder carry some risk of worsening metabolic parameters.
The study was conducted at 46 study centers in the United States, although only 31 study centers enrolled patients in the 40-week extension phase. Patients with acute bipolar I mania, manic or mixed (DSM-IV-TR criteria; Young Mania Rating Scale score ≥ 20), who required hospitalization were randomly assigned to double-blind aripiprazole (15-30 mg/d), lithium (900-1500 mg/d), or placebo for 3 weeks. Patients treated with aripiprazole or lithium continued treatment to week 12, after which they could enter a double-blind 40-week extension phase. Patients were enrolled in the 12-week acute treatment phase between April 2004 and July 2006; the first patient entered extension treatment in October 2004, and the last patient completed treatment in May 2007. Changes in metabolic parameters were compared between patients treated with aripiprazole or lithium for up to 52 weeks using last observation carried forward and analysis of covariance. Analysis stratified by baseline body mass index (BMI) was also conducted.
Modest increases in body weight were observed in both groups: +0.97 kg (2.1 lb) for aripiprazole (n = 127) and + 0.74 (1.6 lb) for lithium (n = 136), P = .60. A significant difference in body weight increase was observed only among patients with a BMI < 25: + 2.66 kg (5.9 lb) for aripiprazole (n = 35) and + 0.40 kg (0.9 lb) for lithium (n = 37), P = .02. Mean changes from baseline to week 52 in fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasma glucose, triglycerides, or insulin (last observation carried forward) were small in both aripiprazole and lithium treatment groups; no significant differences were observed. Mean laboratory values were within the normal or borderline range for both treatment groups across all BMI categories.
Comparably modest and similar changes in metabolic parameters were observed in patients with bipolar disorder treated for up to 1 year with either lithium or aripiprazole.
clinicaltrials.gov Identifier: NCT00095511.
代谢风险因素，即代谢综合征，包括肥胖、糖尿病、血脂异常和高血压，在双相情感障碍患者中比在普通人群中更为常见。此外，用于治疗双相情感障碍的药物有使代谢参数恶化的风险。
该研究在美国的46个研究中心进行，不过在40周的延长期仅有31个研究中心招募了患者。患有急性双相I型躁狂、躁狂或混合发作（符合《精神疾病诊断与统计手册第四版，修订版》标准；青年躁狂评定量表评分≥20）且需要住院治疗的患者被随机分配至双盲阿立哌唑组（15 - 30毫克/天）、锂盐组（900 - 1500毫克/天）或安慰剂组，为期3周。接受阿立哌唑或锂盐治疗的患者持续治疗至第12周，之后可进入双盲的40周延长期。患者于2004年4月至2006年7月纳入12周的急性治疗期；首位患者于2004年10月开始延长期治疗，最后一位患者于2007年5月完成治疗。采用末次观察结转法和协方差分析，比较接受阿立哌唑或锂盐治疗长达52周的患者的代谢参数变化。还进行了按基线体重指数（BMI）分层的分析。
两组患者体重均有适度增加：阿立哌唑组（n = 127）增加0.97千克（2.1磅），锂盐组（n = 136）增加0.74千克（1.6磅），P = 0.60。仅在BMI < 25的患者中观察到体重增加存在显著差异：阿立哌唑组（n = 35）增加2.66千克（5.9磅），锂盐组（n = 37）增加0.40千克（0.9磅），P = 0.02。阿立哌唑和锂盐治疗组从基线到第52周空腹总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血糖、甘油三酯或胰岛素水平（末次观察结转）的平均变化均较小；未观察到显著差异。两个治疗组所有BMI类别的平均实验室值均在正常或临界范围内。
用锂盐或阿立哌唑治疗长达1年的双相情感障碍患者，代谢参数出现了相当适度且相似的变化。
美国国立医学图书馆临床试验注册中心标识符：NCT00095511 。
