再普乐治疗双相情感障碍

再普乐治疗双相情感障碍,双相障碍: 概述,诊断会有困难1-2 治疗困难 1-2通常需要多种药物治疗 3患病率与死亡率高 1-2,1. McElroy SL and Keck PE, Biol Psych 2000; 539-557.2. Thase MD and Sachs GS, Biol Psych 2000; 558-572.3. APA Bipolar Guidelines Am J Psych 2002;159 (Suppl4):1-50.,双相障碍的患病情况,90% 为复发性自杀危险性大（死亡率11-19%）功能恢复滞后于症状的恢复反复发作可导致进行性的功能衰退复发次数可影响以后的治疗效果及预后,1. Dion G et al. Hosp and Community Psych 1988;39(6);652-657.2. Goodwin FK. Jamison KR: Manic Depressive Illness 1990.3. Keck PE Jr, et al. Am J Psych 1998; 155(5):646-652.,双相障碍的流行病学,双相I型的患病率为 1.21-1.6% 2 双相谱系障碍的患病率为2.6-6.5% 3首诊时10人中有7人被误诊4有抑郁症状的患者中，有30% 可能是双相障碍5,Goodwin FK and Jamison KR, Manic-Depressive Illness 1990. Kessler RC, et al. Arch Gen Psychiatry 1994;51:8-19. Angst J. J Affect Dis. 1998;50:143-151. National Depressive and Manic-Depressive Association (NDMDA) Constituent Survey, Chicago, IL, 2001. Manning JS. Comprehensive Psychiatry 1997;38:102-108.,情绪低落,亚临床阶段,抑郁阈值,躁狂阈值,情绪高涨,严重程度,双相障碍的病程,Manning JS, et al. Prim Care Companion J Clin Psych 2002;4(4):142-150.,混合性躁狂和快速循环,混合性躁狂同时存在抑郁和躁狂症状可占所有双相I型的 30-40% 女性 男性快速循环4 次发作/年女性3倍于男性超快速循环: 4 次/月,1. Evans DL. J Clin Psych 2000;61 (Suppl 13):26-31. 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC. American Psychiatric Association, 2000.,双相躁狂的治疗目标,控制危险的症状 自杀、激越、精神病症状稳定心境 控制躁狂症状 对抑郁、焦虑和精神病性症状也有效恢复病前功能对患者无损害不影响患者的日常生活,治疗躁狂理想的心境稳定剂,治疗躁狂快速起效对精神病性症状有效疗效广泛（如混合型、快速循环型）缓解抑郁症状,改善认知功能长期治疗有效安全、耐受性好使用简单方便,再普乐治疗双相障碍的指征,急性躁狂严重急性躁狂或混合发作:合用锂盐或丙戊酸盐轻、中度：可单用再普乐快速循环型双相抑郁，伴精神病性症状-联合用药难治性抑郁症巩固维持治疗,Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision). Am J Psychiatry. 2002;159(Suppl4):1-50.Grunze H, Kasper S, Goodwin G et al. World J Biol Psychiatry 2003;4:5-13.中国精神障碍治疗指南（2003）,心境障碍与精神病性障碍的交叉重叠,抑郁症,精神病性障碍,双相障碍,难治性抑郁症,双相抑郁症,伴精神病性症状的抑郁症,再普乐对神经递质的作用（可能的药理机制）,再普乐治疗急性躁狂,丙戊酸钠或碳酸锂加用奥氮平治疗急性期I型双相心境障碍,Tohen M. et al (2002),6周、双盲、安慰剂对照、急性期治疗研究 (N = 344)入组标准:以前有2次抑郁、躁狂、或混合发作 在第一、第二次诊治时，YMRS 总分 16 单用碳酸锂或丙戊酸钠治疗2 周无效者(A) 合并治疗 (奥氮平+碳酸锂或丙戊酸钠) (B) 单一治疗 (单用碳酸锂或丙戊酸钠).剂量:奥氮平:起始剂量: 10 mg/d剂量范围: 5 20 mg/d平均剂量: 10.4 mg/d碳酸锂:血锂浓度0.6 1.2 mEq/L (mmol/L)丙戊酸钠:血浓度50 125 g/mL (347 866 mol/L),疗效:YMRS 总分,-14,-12,-10,-8,-6,-4,-2,0,平均变化,从基线到终点,奥氮平合并治疗, n = 220,锂+/丙戊酸钠 单一治疗, n = 114,-13.11,-9.10,*,基线: 22.31 22.67,*p = .003,奥氮平合并治疗组 YMRS 总分有显著较多改善,每周分析: YMRS 总分从基线到终点平均改变 (LOCF),-20,-15,-10,-5,0,0,1,2,3,4,5,6,双盲治疗周数,*p .05,*,从5周起，奥氮平合并治疗病例有较多 LOCF 平均改善,*,平均改变从基线到终点,奥氮平合并治疗, n = 220,锂+/丙戊酸钠单一治疗, n = 114,每周分析: YMRS 总分方差分析,-15,-10,-5,0,平均 (最小方差),双盲治疗的周数,*,*,*,*,*p .05 *p .01*p .001,方差分析表明, 在第1、3、5、及6周末，奥氮平合并治疗病例的改善更为显著,奥氮平合并治疗, n = 220,锂+/丙戊酸钠单一治疗, n = 114,锂+/丙戊酸钠 单一治疗, n = 114,显效率:YMRS 总分减少50%,44.7%,67.7%,0,10,20,30,40,50,60,70,80,*p .001,病例 (%),奥氮平合并治疗, n = 220,有效者,*,奥氮平合并治疗组的2/3以上病例有显效，明显多于单一治疗组,-16,-14,-12,-10,-8,-6,-4,-2,0,0,10,20,30,40,50,60,缓解率p=.152,病人百分比,YMRS评分变化,比 安慰剂,比 安慰剂,3 周,4 周,p=.019,-14.78,n=70,n=66,比丙戊酸盐,合用比单用,3 周,6 周,p.001,p=.003,-10.39,n=125,n=114,n=220,n=234,n=219,n=56,p=.028,比 氟哌啶醇6 周,再普乐,安慰剂,丙戊酸盐,Li or VPA,OLZ+Li or VPA,氟哌啶醇,再普乐治疗急性躁狂,再普乐治疗非精神病性躁狂的疗效优于丙戊酸盐,Tohen M, et al. Am J Psychiatry. 2002;159:1011-1017.,-8.7,-14.1*,丙戊酸盐 (n=74),再普乐 (n=63),*p.001,3周时的 YMRS 评分改善 (LOCF),治疗前:,25.7,26.1,-14,-12,-10,-8,-6,-4,-2,0,合用再普乐对躁狂发作或混合发作的抑郁症状的疗效优于单用锂盐或丙戊酸盐,-6,-5,-4,-3,-2,-1,0,-4.98 *,-0.89,Baseline:,合用再普乐 (n=220),单用锂盐或丙戊酸盐 (n=114),* p.001,HAM-D Mean Change,Baseline to Endpoint (6 Weeks),Improvement,Tohen M, et al. Arch Gen Psychiatry. 2002;59(1):62-69.,14.52,13.54,再普乐用于双相障碍的巩固维持治疗,再普乐长期治疗的依从性好于锂盐（1年随访）,病例%,完成随访*,不良反应,疗效差,再普乐 12 mg/day (n=217),锂盐1103 mg/day (n=214),Slide Modified:,Review:,Reviewer Memo:,Source:,Memo:,*p=.004,n=41,n=55,n=34,n=31,n=70,n=101,Tohen M, et al. Presented at: Stanley Bipolar Meeting; September 11-14, 2002; Freiberg, Germany.,再普乐预防躁狂发作优于锂盐预防抑郁发作等同于锂盐,复发病例%,*YMRS or HAMD-21 Total scores 15.Tohen M, et al. Presented at: Stanley Bipolar Meeting; September 11-14, 2002; Freiberg, Germany.,0,10,20,30,40,50,14.3%,28.0%,p=.055,p=.895,p.001,总复发,复发为抑郁,复发为躁狂,15.4%,16.1%,38.8%,30.0%,再普乐 12 mg/day (n=217),再普乐1103 mg/day (n=214),*,再普乐对躁狂症维持治疗的疗效优于丙戊酸盐,*Days 2 and 3; weeks 2-15, week 23, weeks 31-47.Tohen MF. Presented at: 155th APA Annual Meeting; May 18-23, 2002; Philadelphia, PA.,-25,-20,-15,-10,-5,0,0,5,10,15,20,25,30,35,40,45,再普乐 (n=125),丙戊酸盐 (n=126),YMRS量表总分变化,治疗时间（周）,*,*,*,*,*,*,*,*,*,*,*,*,p=.002 overall *p.05,躁狂或抑郁复发前的时间（天),0,100,200,300,400,500,0,20,40,60,80,100,OLZ plus Li or VPA, (n=30),Li or VPA, (n=38),p=.023,Time to recurrence into either pole following symptomatic remission of mania (YMRS 12) and depression (HAMD-21 8), was significantly longer for the olanzapine cotherapy group compared to the monotherapy group (estima