辅助治疗重性抑郁

阿立哌唑（安律凡） 辅助治疗重性抑郁,1. 2008, Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan,2.Abilify(aripiprazole)tablets:US prescribing information.Princeton(NJ):Bristol-Myers Squibb,2008 Feb,阿立哌唑是美国FDA批准的第一种用于成人MDD辅助治疗的非典型抗精神病药物,ABILIFY is indicated for use as an adjunctive treatment to antidepressantsfor Major Depressive Disorder,阿立哌唑（安律凡 ）用于辅助治疗成人抑郁症,2个6周的研究(CN138-139 and CN138-163) 评价抗抑郁药物联合使用阿立哌唑或安慰剂的疗效及安全性治疗重性抑郁：经过1-3个抗抑郁药物治疗疗效不佳且其中一个是前瞻性的观察研究两个研究取得了一致的结果: 阿立哌唑组的MADRS分数改变显著优于安慰剂组,3,阿立哌唑对重性抑郁的辅助治疗,1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,4,Phase A筛查期,Phase B前瞻性治疗,Phase C治疗无效的患者随机,筛查(1-4 wks),指定 ADT + 安慰剂单盲 (8 wks),Week 08 14,阿立哌唑+ ADT(6 wks),Phase B+治疗有效非随机，单盲,安慰剂 + ADT(6 wks),单盲 安慰剂 + ADT(6 wks),S-CIT(10 or 20 mg),FLUO(20 or 40 mg),PAR CR(37.5 or 50 mg),SERT(100 or 150 mg/day),VEN XR(150 or 225 mg/day),研究设计,1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,重性抑郁发作患者：经过Phase B的8周治疗效果不佳效果不佳是指HAM-D17 14与基线相比减分率50% CGI-I 3,5,CGI-I=Clinical Global ImpressionImprovement; HAM-D 17=17-item Hamilton Rating Scale for Depression.,入组标准：Phase C,1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,6,起始剂量5mg，使用不少于1周后，再进行剂量上调LOCF=末次观察向前结转基线时MADRS平均总分为26分,1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,阿立哌唑使MADRS显著下降,PBO + ADT (n=172),ARI + ADT (n=181),*P.001 vs PBO,平均改变 (LOCF),Weeks,*,*,*,*,*,CN138-1391,Weeks,*P.01 vs PBOP.001 vs PBO,*,CN138-1632,PBO + ADT (n=184),ARI + ADT (n=185),7,*P0.05 vs PBO; * P0.01 vs PBORemission = MADRS Total score 10 ，MADRS = MontgomeryAsberg Depression Rating Scale; LOCF = Last Observation Carried Forward,MADRS治愈率（LOCF）(CN138-139),更高的减分率(26.0% vs 15.7% 结束点, P0.05),安慰剂阿立哌唑,*,*,*,*,减分率 (%),0,5,10,15,20,25,30,1,2,3,4,5,6,周,1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,8,安慰剂阿立哌唑,*,*,*,*,*,*,有效率 (%),0,5,10,15,20,25,30,35,40,1,2,3,4,5,6,周,*P0.05 vs PBO; *P0.01 vs PBO; *P0.001 vs PBO.Response = 50% decrease from end of prospective treatment phase in MADRS Total score.MADRS = Montgomery-Asberg Depression Rating Scale; LOCF = Last Observation Carried Forward.,MADRS有效率（LOCF）(CN138-139),1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,更高的有效率(33.7% vs 23.8% 结束点, P0.05),9,*,*,*,*,*,*,安慰剂,阿立哌唑,至基线的平均改变,*P0.01 vs PBO; *P0.001 vs PBO.CGI-S scores at end of prospective treatment phase: PBO 4.1; ARI 4.1LOCF = Last Observation Carried Forward; CGI-S = Clinical Global Impression-Severity of Illness; CGI-I = Clinical Global Impression-Improvement,-1.2,-1,-0.8,-0.6,-0.4,-0.2,0,0,1,2,3,4,5,6,周,CGI-S的改变（LOCF）(CN138-139),1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,10,P=0.055,P=0.976,*P=0.030,*P=0.017,总平均数,工作/学习,社会生活,家庭生活,n= 164,n=130,n=164,n=164,n=167,n= 127,n=167,n=167,*P0.05.SDS = Sheehan Disability Scale,SDS 分数改变(LOCF) (CN 138-139),1. Berman RM et al. J Clin Psychiatry. 2007;68:843-853; 2. Data on file: CN138-163.,11,慢性病人VS.非慢性病人（CN138-139）,慢性病人：抑郁发作，症状发作完全符合诊断标准，持续2年以上,阿立哌唑组MADRS改变显著优于安慰剂组(-8.9 vs -5.9; P=0.016),12,*P0.05; *P0.001MADRS=Montgomery-Asberg Depression Rating Scale; LOCF=Last Observation Carried Forward.MADRS Total scores at end of prospective treatment phase: PBO 26.4; ARI 26.5.Vertical bars = Standard Error.,*,*,*,*,*,0,1,2,3,4,5,6,7,8,9,10,11,12,0,1,2,3,4,5,6,ARI,PBO,慢性病人MADRS改变（LOCF）(CN138-139),阿立哌唑组MADRS改变显著优于安慰剂组(-8.8 vs -5.9; P=0.012),13,*P0.05; *P0.01MADRS=Montgomery-Asberg Depression Rating Scale; LOCF=Last Observation Carried Forward.MADRS Total scores at end of prospective treatment phase: PBO 25.6; ARI 26.6.Vertical bars = Standard Error.,*,*,*,*,*,非慢性病人的MADRS分数改变（LOCF）(CN138-139),阿立哌唑治疗精神疾病FDA 推荐剂量方案,Once-daily dosingMay be taken with or without foodThe safety of doses of ABILIFY above 30 mg/day has not been evaluated in clinical trialsPrescriptions for ABILIFY should be written for the smallest dose consistent with good patient management to reduce the risk of overdoseDosing adjustments of up to 5 mg/day should occur gradually at intervals of no