奎硫平治疗双相情感障碍临床分析

目的：评价奎硫平单药治疗及联合碳酸锂治疗双相情感障碍躁狂发作的疗效和安全性。方法：78例双相情感障碍躁狂发作患者随机分成奎硫平单药治疗组（研究组）和奎硫平联合碳酸锂治疗组（对照组）各39例。观察4周。于治疗前以及治疗1、2和4周分别采用杨氏躁狂量表（YMRS）、阳性与阴性症状量表（PANSS）评价疗效;采用不良事件量表、SimpsonAngus量表、Barnes静坐不能评定量表及不自主运动量表评价药物安全性。结果：治疗4周,研究组痊愈率63.89%,有效率94.44%;对照组分别为66.67%和94.44%,两组比较,差异无统计学意义（P〉0.05）。两组YMRS评分治疗前差异无统计学意义（P〉0.05）,治疗后各周均有显著下降（P均〈0.01）;两组比较,差异无统计学意义（P〉0.05）。研究组不良反应总发生率显著低于对照组（χ2=4.06,P〈0.05）。结论：奎硫平单药治疗双相情感障碍躁狂发作与奎硫平联合碳酸锂治疗疗效相同,且单药治疗不良反应发生率更低。     

喹硫平（思瑞康）单药或联合锂盐治疗双相躁狂发作的疗效和安全性

目的 比较喹硫平单药或联合锂盐治疗双相躁狂患者的疗效和安全性.方法 24例患者随机给予喹硫平单药或联合锂盐治疗,于基线、治疗第1、2、3、4周末,分别采用临床总体印象量表一双相障碍版(CGI-BP)、Young躁狂量表(YMRS)、阳性和阴性症状量表(PANSS)评定疗效.基线和终点时进行生化、血常规、尿常规以及心电图检查,以评价安全性.结果 试验组和对照组的YMRS和PANSS的得分随着治疗时间而逐渐下降,每组各时间点之间存在统计学显著性(P<0.01),但是两组之间比较无统计学意义(P>0.05).两组在有效率、痊愈率和病情改善方面比较无统计学意义(P>0.05),两组均未出现严重的不良事件.结论 喹硫平(思瑞康)单药治疗双相障碍躁狂急性发作的疗效同联合碳酸锂治疗相当,但安全性高.     

奎硫平治疗精神科双相急性躁狂症患者的疗效及安全性

目的本研究诣在探讨喹硫平治疗双相心境障碍急性躁狂发作的临床效果及安全性。方法选取笔者科室92例确诊双相心境障碍急性躁狂发作患者依据入院顺序分为喹硫平组和碳酸锂组各46例,两组患者均连续治疗6周,观察两组患者的临床治疗效果及不良反应发生率差异。结果治疗后第3周、第6周喹硫平组的躁狂评分(18.5±3.6)分、(11.5±2.4)分均显著的低于碳酸锂组的(21.6±3.9)分、(14.3±3.0)分(P0.05)。治疗后第3周、第6周喹硫平组的躁狂评分减分率(24.18±8.17)%、(52.87±21.64)%均显著的高于碳酸锂组的(13.60±7.03)%、(42.80±19.33)%(P0.05)。治疗后第6周喹硫平组的愈显率(69.57%)均显著的高于碳酸锂组的(91.30%)(P0.05)。喹硫平组的不良反应率(10.87%)显著的低于碳酸锂组的(28.26%)(P0.05)。结论喹硫平治疗双相心境障碍急性躁狂发作的临床效果确切,不良反应发生率更低。     

碳酸锂单用与合并阿立哌唑治疗双相障碍I型躁狂发作患者的随机对照研究

目的:探讨碳酸锂单用及合并阿立哌唑治疗双相障碍I型躁狂发作患者的疗效和安全性。方法:86例门诊双相障碍I型躁狂发作患者被随机分为联合组(碳酸锂+阿立哌唑治疗)和单药组(碳酸锂单药治疗),疗程8周。分别在治疗前、治疗2、4、8周进行杨氏躁狂量表(YMRS)和汉密顿抑郁量表(HAMD)-17项评定,采用治疗中出现的症状量表(TESS)评定不良反应。结果:治疗前两组YMRS评分差异无统计学意义;治疗2、4、8周后联合组YMRS减分值明显高于对照组(P0.05或P0.01);治疗前后两组HAMD均7分;两组TESS评分差异无统计学意义。结论:碳酸锂联合阿立哌唑治疗双相障碍I型躁狂发作较单用碳酸锂起效快,症状改善更明显,且未见不良反应明显增加。     

碳酸锂联合富马酸喹硫平片或丙戊酸镁缓释片治疗双相情感障碍躁狂发作的疗效

目的研究富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂治疗双相情感障碍躁狂发作的疗效。方法将100例双相情感障碍躁狂发作的患者随机、双盲分为对照组和观察组,50例/组,对照组采取丙戊酸镁缓释片联合碳酸锂治疗,观察组采用富马酸喹硫平片联合碳酸锂治疗。将两组双相情感障碍躁狂发作患者的倍克-拉范森躁狂量表(BRMS)评分、阳性和阴性症状量表(PANSS)评分、认知功能、临床效果、不良反应发生情况进行比对。结果观察组患者治疗后的BRMS评分及PANSS评分均低于对照组,差异具有统计学意义(P0.05);治疗后的言语记忆测验(HVLT-R)、持续操作测验(CPT)评分高于对照组,差异具有统计学意义(P0.05);两组的临床总有效率和不良反应发生率无统计学差异(P0.05)。结论在治疗双相情感障碍躁狂发作方面,富马酸喹硫平片联合碳酸锂、丙戊酸镁缓释片联合碳酸锂进行治疗均可取得较好的疗效,安全性较高,但是富马酸喹硫平片联合碳酸锂在改善患者认知功能及临床症状方面效果更好。     

富马酸喹硫平片或丙戊酸镁缓释片联合碳酸锂治疗双相情感障碍躁狂发作的临床研究

目的比较富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂治疗双相情感障碍躁狂发作的临床疗效。方法随机数字表法将135例双相情感障碍躁狂发作患者分为3组各45例,对照组采取碳酸锂单独治疗,观察1组行富马酸喹硫平片联合碳酸锂治疗,观察2组采取丙戊酸镁缓释片联合碳酸锂治疗,比较3组临床疗效、不良反应、治疗前后躁狂量表(BRMS)评分、阳性阴性症状量表(PANSS)评分及认知功能情况。结果观察1、观察2组治疗28d BRMS评分、PANSS评分、CPT评分较对照组比较差异均有统计学意义(P0.05)。观察1组与观察2组治疗7d BRMS评分、PANSS评分分别比较显著差异(P0.05)。观察1组、观察2组治疗总有效率分别为88.9%、86.7%均显著高于对照组的66.7%(P0.05)。3组不良反应发生率比较差异无统计学意义(P0.05)。结论富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂均能明显改善双相情感障碍躁狂症发作患者躁狂症状,疗效明确,能有效促进患者部分认知功能恢复,且富马酸硫平片联合碳酸锂治疗起效更快。     

奎硫平与氯丙嗪辅助碳酸锂治疗躁狂发作疗效分析

目的:探讨奎硫平与氯丙嗪分别合并碳酸锂治疗躁狂发作的疗效和安全性.方法:将符合条件的46例躁狂患者随机分成两组,进行6周治疗.采用Beck-Rafaelsen躁狂量表(BRMS)评定疗效,以副反应量表(TESS)及实验室有关辅助检查评价安全性.结果:治疗结束时两组BRMS的减分率无显著差异,奎硫平组在治疗第1周末的减分率比氯丙嗪组显著;奎硫平组心血管症状及神经毒性反应均较氯丙嗪组低.结论:奎硫平合并碳酸锂治疗躁狂发作与氯丙嗪合并碳酸锂的疗效相似,前者起效较快且安全性较高.     

奎硫平单用与联合碳酸锂治疗女性躁狂发作患者的对照研究

目的:观察奎硫平对女性躁狂发作的急性期及维持期治疗的疗效及安全性。方法:将61例女性躁狂发作患者随机分为研究组(30例)和对照组(31例),两组均给予奎硫平0.4~0.8 g/d,对照组在此基础上加用碳酸锂1.0~1.75 g/d,治疗6周。于治疗前后采用Bech-Rafaelsen躁狂量表(BRMS)评定疗效;于治疗后采用治疗中出现的症状量表(TESS)评定不良反应。结果:治疗后BRMS评分两组间比较差异无统计学意义(t=-0.41~1.17,P均0.05);研究组痊愈率69.0%,对照组痊愈率73.3%,两组痊愈率差异无统计学意义(χ2=0.77,P均0.05)。两组不良反应比较,差异无统计学意义(χ2=0.01~1.51,P均0.05)。结论:奎硫平单用与奎硫平联合碳酸锂治疗女性躁狂发作的疗效及安全性相当。     

奎硫平合并心境稳定剂治疗躁狂发作的疗效

目的探讨奎硫平合并碳酸锂或丙戊酸钠治疗躁狂发作的疗效和安全性。方法将符合CCMD-3躁狂发作或分裂情感障碍诊断标准的68例研究对象随机分成两组,研究组应用奎硫平合并碳酸锂或丙戊酸钠,对照组单一使用碳酸锂或丙戊酸钠,治疗观察6周。采用Beck—Rafaelsen躁狂量表(BRMS)评定疗效,以副反应量表(TESS)及实验室有关辅助检查评价安全性。结果奎硫平组在治疗第1周末的减分率比对照组显著,这种差异在1～6周一直存在,而且第6周结束后的临床痊愈率也显著高于对照组。奎硫平组痊愈率为69．7%,对照组为19．2%(x~2=14．85,P＜0．01)。两组均没有严重的药物不良反应,因无疗效和不良反应导致的脱落率两组差异无显著性。奎硫平组脱落率为8．3%,对照组为18．7%(x~2=1．58,P＞0．05)。结论奎硫平合并碳酸锂或丙戊酸钠治疗躁狂发作的疗效比较理想,比单一使用心境稳定剂好。     

碳酸锂、丙戊酸钠及奎硫平对双相障碍患者认知功能的影响

目的:探讨碳酸锂,丙戊酸钠和奎硫平对双相障碍患者认知功能的影响。方法:110例稳定期双相障碍I型患者分成4组,分别是碳酸锂组26例,丙戊酸钠组24例,碳酸锂+奎硫平组27例和丙戊酸钠+奎硫平组33例。采用数字符号,连线测验,数字广度,视觉再生,言语流畅性测验,威斯康星卡片分类测验(WCST)和汉诺塔检测认知功能,比较组间认知功能的差异。结果:Spearman相关分析显示,病程与所有认知功能指标均无显著相关(P均>0.05)。方差分析显示,汉诺塔计划时间组间差异有统计学意义(F=3.5,P<0.05)。LSD检验表明,碳酸锂组的汉诺塔计划时间成绩分别比丙戊酸钠组,碳酸锂+奎硫平组和丙戊酸钠+奎硫平组差,差异有统计学意义(P<0.05)。结论:碳酸锂可能对稳定期双相障碍患者的某些执行功能有损害。     

A double-blind,randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania

OBJECTIVES: This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated. METHOD: Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly. RESULTS: The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group. CONCLUSIONS: The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.     

A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder

OBJECTIVE: To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder. METHOD: In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002. RESULTS: More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events. CONCLUSIONS: Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.     

A Naturalistic, Single-blind Comparison of Rapid Dose Administration of Divalproex ER Versus Quetiapine in Patients with Acute Bipolar Mania

Objective: When treating acute bipolar mania, the speed of onset of anti-manic effects is crucial. Quetiapine and divalproex ER are widely used agents to treat acute mania. Rapid dose administration regimens for divalproex ER and for quetiapine have been described. We conducted a naturalistic, head-to-head, pilot study comparing the efficacy and safety of rapidly titrated divalproex ER and quetiapine in acutely manic inpatients, with the primary outcome being improvement within the first seven days.Method: Thirty consenting bipolar patients with acute mania (Young Mania Rating Scale >17 ) needing hospitalization due to acute mania were randomized to receive rapidly loaded divalproex ER (30mg/kg/day) or rapidly titrated quetiapine (200mg Day 1, raised by 200mg/day up to 800mg as tolerated). Assessments were made on Day 1 (baseline), Day 3, Day 7, Day 14, and Day 21 and included Young Mania Rating Scale, Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement, and Montgomery-Asberg Depression Rating Scale. Raters but not patients or treating physicians were blinded (single-blinded study).Results: Subjects in both treatment groups exhibited significant and rapid improvement in their mania starting at Day 3 with few significant adverse effects; however, there were no significant differences in the degree or rate of improvement between the two treatment groups in any of the efficacy or adverse effects scales.Conclusion: Results of this small study indicate that rapid-dose administration of both quetiapine and divalproex ER produce rapid improvement in acute mania within the first seven days and both seem to be well tolerated.     

Quetiapine in acute mania: a case report (with a six-month follow-up)

Quetiapine is an effective and well-tolerated antipsychotic. To date, experience with quetiapine in bipolar disorders is very limited and information on the use in acute patients is lacking. A patient with a DSMIV diagnosis of acute mania intolerant to lithium and to neuroleptics was treated with quetiapine. The daily dosage of quetiapine was gradually titrated up to 600 mg t.i.d. Quetiapine was effective, as evidenced by rating scale scores of the BPRS, YMRS and CGI, which dropped by 91% and 94% respectively from baseline (devoid of relevant side-effects). Quetiapine seems to be a promising agent for the treatment of manic episodes in bipolar disorders, although controlled trials are needed.     

A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania

OBJECTIVE: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. METHOD: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days for this double-blind study, which was conducted from July 2002 through January 2004. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) score across the study period. RESULTS: Repeated measures analysis of variance using the last-observation carried forward data indicated no statistically significant group difference in YMRS scores across the 28 days of the study (p = 0.3). Mixed regression analyses (comparison of slopes) revealed that improvement in YMRS scores occurred more rapidly in the quetiapine than in the divalproex group for both the last-observation carried forward (p = 0.01) and observed data (p = 0.03). Response and remission rates were significantly greater in the quetiapine than in the divalproex group (p < .03). Rates of adverse events did not differ significantly between groups. CONCLUSIONS: The results suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms associated with adolescent bipolar disorder; however, a quicker reduction of manic symptoms may occur with quetiapine as compared with divalproex. Quetiapine may be useful as monotherapy for the treatment of adolescents with manic or mixed episodes, although placebo-controlled studies are necessary.     

Long-term treatment of adjunctive quetiapine for bipolar mania

This study evaluated the overall effectiveness and tolerability of adjunctive quetiapine as a continuation therapy for the long-term treatment of bipolar mania. Twenty-three patients were enrolled in this study and received quetiapine add-on treatment in combination with their existing or new mood stabilizers. The clinical assessment was carried out using the Young Mania Rating Scale (YMRS), Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale scores-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly from the baseline to the endpoint by 89.7% and 78.3%, respectively (p < 0.0001; p < 0.0001). By the end of the study, 22 patients showed at least 50% improvement in the YMRS score. This study suggests that quetiapine can be used as an adjunct in the long-term treatment of bipolar mania.     

Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study

OBJECTIVE: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania. METHODS: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL. RESULTS: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension. CONCLUSIONS: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.     

A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes

BACKGROUND: Carbamazepine has been used to treat mania for over 2 decades. Most evaluations of carbamazepine have had important limitations, such as absence of a parallel placebo group, small sample size, or the confounding influence of concomitant treatment. All studies have used conventional, immediate-release carbamazepine formulations. We assessed the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ; SPD417) in bipolar disorder patients with manic or mixed episodes. METHOD: Following a single-blind placebo lead-in, DSM-IV-defined bipolar disorder patients with manic or mixed episodes were randomly assigned to receive ERC-CBZ (N = 101) or placebo (N = 103) for 3 weeks. Patients were hospitalized through the first 7 days of the double-blind period. ERC-CBZ was initiated at 400 mg/day and increased, as necessary and tolerated, up to 1600 mg/day. Efficacy was assessed weekly with the Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression (HAM-D). Data were gathered from December 1999 to June 2001. RESULTS: Ninety-six (47.1%) of 204 patients completed the study. The mean +/- SD final ERC-CBZ dose was 756.44 +/- 413.38 mg/day with a mean plasma drug level of 8.9 microg/mL. Starting at week 2, ERC-CBZ was associated with significantly greater improvements in YMRS (p =.032) using last-observation-carried-forward analyses. At end point, the responder rate (patients with at least a 50% decrease in YMRS score) also favored ERC-CBZ (41.5% vs. 22.4%; p =.0074). In a post hoc analysis of mixed patients, HAM-D score was significantly improved in patients remaining on ERC-CBZ treatment on day 21 (p =.01). Adverse events occurring more frequently in the ERC-CBZ group than in the placebo group included dizziness, nausea, and somnolence. CONCLUSION: We found ERC-CBZ to be effective in the first large, randomized, double-blind, placebo-controlled parallel trial of carbamazepine monotherapy in acute mania. This trial provides important additional evidence supporting the use of carbamazepine in acute mania.     

Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials

OBJECTIVE: To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. METHODS: In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study. RESULTS: Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p < or = 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. CONCLUSIONS: These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.