奥氮平单药与联合碳酸锂治疗双相障碍躁狂发作患者的对照研究

目的:比较奥氮平单药与奥氮平联合碳酸锂治疗双相躁狂或混合发作患者的疗效与安全性. 方法:60例双相障碍Ⅰ型躁狂发作或混合性发作患者随机分为单用药组29例和合用药组31例.分别给予奥氮平单药和奥氮平联合碳酸锂治疗.疗程4周.于基线时,治疗l,2,3和4周,分别采用临床总体印象量表-双相障碍版、Young躁狂量表(YMR...     

新型抗精神病药对躁狂发作的辅助治疗

目的:研究利培酮与奥氮平合并碳酸锂治疗双相障碍躁狂发作的疗效与安全性.方法:66例双相障碍躁狂发作患者随机分为两组,使用碳酸锂治疗,分别合用利培酮或奥氮平,疗程6周.以Bech-Rafaelsen躁狂量表(BRMS)、大体评定量表(GAS)、疗效总评量表病情严重程度(CGI-SI)、副反应量表(TESS)进行评价.结果:利培酮组与奥氮平组疗效相仿,不良反应有不同.结论:利培酮与奥氮平可作为治疗躁狂症的辅助药物.     

奥氮平与碳酸锂对双相情感障碍患者躁狂症状、血清尿酸水平的影响及安全性比较

目的比较奥氮平与碳酸锂对双相情感障碍躁狂发作患者症状、血清尿酸水平的影响及安全性。方法对我院治疗的72例双相情感障碍躁狂发作患者进行研究。按照随机数字表发将患者分为观察组和对照组,对照组给予碳酸锂治疗,观察组给予奥氮平治疗。比较两组患者治疗前后的Beck-Rafaelsen躁狂量表(BRMS)评分、血清尿酸水平以及不良反应发生情况。结果两组患者治疗后,BRMS评分较治疗前均有显著降低(P0.05),且观察组患者各时间段的BRMS评分均显著低于对照组各时间段的BRMS评分(P0.05)。两组患者治疗前后及各时间点的血清尿酸水平比较差异均无统计学意义(P0.05)。对两组患者随访8周,对照组的不良反应发生率与观察组相比无显著差异(P0.05)。结论奥氮平治疗双相情感障碍躁狂发作的疗效确切,安全性较高。未发现其对血清尿酸水平的显著影响。     

奥氮平与碳酸锂治疗躁狂发作的对照研究

目的：比较奥氮平与碳酸锂治疗双相Ⅰ型障碍急性躁狂发作的疗效及安全性。方法：57例符合美国精神障碍诊断与统计手册第4版（DSM-Ⅳ）双相Ⅰ型障碍急性躁狂发作患者随机分为奥氮平组与碳酸锂组。治疗6周。以Bech-Rafaelsen躁狂量表（BRMS）、大体评定量表（GAS）、临床疗效总评量表（CGI）评估疗效,治疗中出现的症状量表（TESS）评定不良反应。结果：奥氮平与碳酸锂疗效相当（P〉0.05）,各有其不良反应。治疗前后TESS量表分,两组间差异无显著性（P〉0.05）。结论：奥氮平治疗双相Ⅰ型障碍急性躁狂发作,疗效和不良反应与碳酸锂无明显差异。     

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。     

奥氮平合并碳酸锂治疗躁狂发作临床对照研究

目的研究奥氮平合并碳酸锂与氟哌啶醇合并碳酸锂治疗躁狂发作的疗效及安全性。方法将72例躁狂发作患者随机分为两组,其中奥氮平组和氟哌啶醇组各36例,进行为期6周的对照研究,采用躁狂量表和不良反应症状量表评定疗效及安全性。结果奥氮平组与氟哌啶醇组疗效相当(P>0.05),而奥氮平组副作用明显少于氟哌啶醇组。结论奥氮平合并碳酸锂是治疗躁狂发作安全有效的药物。     

氟西汀与碳酸锂预防双相II型障碍重性抑郁发作复燃和转躁对照研究

目的:观察双相II型重性抑郁发作临床症状控制后较长期的单用氟西汀与单用碳酸锂治疗的复燃或转躁情况。方法:对75例双相II型障碍重性抑郁发作临床症状控制的患者随机分成两组,分别单用氟西汀与碳酸锂进行26周的治疗并随访,并进行汉密尔顿抑郁量表(HAMD)、杨氏躁狂量表(YMRS)评定。结果:治疗前1周、治疗2周、10周、18周、26周两组HAMD、YMRS评分两组同期比较差异均无显著性(P>0.05)。氟西汀组亚综合征抑郁和抑郁症复燃率低,碳酸锂组亚综合征轻躁狂和轻躁狂发作率低,两组比较差异均有显著性(P<0.05)。结论:双相II型障碍重性抑郁发作后氟西汀单一治疗比锂盐单一治疗可较好预防复燃,但能增加轻躁狂心境转换的发作。     

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。     

帕利哌酮联合心境稳定剂治疗双相障碍躁狂发作的疗效与安全性研究

目的研究帕利哌酮联合心境稳定剂治疗双相障碍躁狂发作的疗效与安全性。方法200例双相障碍躁狂发作患者分为碳酸锂、丙戊酸钠单药治疗组和帕利哌酮+碳酸锂、帕利哌酮+丙戊酸钠联合治疗组,治疗共6周。于治疗前及治疗后1、2、4、6周末采用临床总体印象量表-双相障碍版(CGI-BP)、Young躁狂量表(YMRS)和副反应量表(TESS)等评定疗效和安全性。结果四组YMRS和CGI-BP较治疗前均有下降(p0.05),联合治疗组下降水平要强于单药治疗组(p0.05),其中帕利哌酮联合丙戊酸钠组在1、2周末下降速度和水平要强于帕利哌酮联合碳酸锂组(p0.05);四组间不良反应发生率无明显差异(p0.05)。结论帕利哌酮缓释片联合碳酸锂或丙戊酸钠能快速有效控制双相障碍躁狂发作,耐受性好。     

齐拉西酮结合丙戊酸钠治疗双相障碍躁狂发作的临床疗效观察

目的探讨齐拉西酮联合丙戊酸钠缓释片治疗双相障碍躁狂发作的临床疗效及安全性。方法选取2013年1月~2017年3月期间在我院接受治疗的100例双相障碍躁狂发作患者作为研究对象,将患者随机分为齐拉西酮组和奥氮平,每组各50例。奥氮平组患者采用丙戊酸钠缓释片联合奥氮平治疗,齐拉西酮组患者采用丙戊酸钠缓释片联合齐拉西酮治疗,治疗8周后,比较两组患者的临床疗效、躁狂评分、不良反应发生率。结果齐拉西酮组的临床总有效率为94%,明显高于奥氮平组的78%(P0.05);治疗后,两组患者的躁狂评分均较治疗前明显降低(P0.05),且齐拉西酮组的躁狂评分显著低于奥氮平组(P0.05);齐拉西酮组的不良反应发生率为4%,奥氮平组的不良反应发生率则为18%,两组比较差异具有统计学意义(P0.05)。结论采用齐拉西酮与丙戊酸钠缓释片联合治疗双相障碍躁狂发作,既可有效缓解患者的躁狂症状,又可减少患者的不良反应发生率。     

Lithium regulates glycogen synthase kinase-3beta in human peripheral blood mononuclear cells: implication in the treatment of bipolar disorder.

BACKGROUND: Bipolar disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3beta (GSK3beta). The mood stabilizer lithium inhibits GSK3beta in vitro and in mouse brain, and this is currently the strongest known potential therapeutic target of lithium. We tested whether lithium modified GSK3beta in vivo or in vitro in peripheral blood mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects. METHODS: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar subjects currently treated with lithium, and 13 lithium-free bipolar subjects. Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated GSK3beta. RESULTS: The level of phospho-Ser9-GSK3beta in PBMCs was regulated by agents that modified kinases and phosphatases acting on GSK3beta and was increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3beta levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy control subjects. CONCLUSIONS: Signaling pathways regulating serine9-phosphorylation of GSK3beta can be studied in human PBMCs. Both in vitro and in vivo therapeutic lithium treatment is associated with a large increase in phospho-Ser9-GSK3beta in PBMCs. Therefore, the inhibitory serine9-phosphorylation of GSK3beta in human PBMCs may provide a biochemical marker to evaluate the association between GSK3beta inhibition and therapeutic responses to lithium treatment.     

喹硫平与碳酸锂单药治疗双相抑郁的随机双盲对照研究

目的研究喹硫平和碳酸锂单药治疗双相抑郁的有效性和安全性。方法为期8周的双盲随机平行可变剂量对照研究。对68例符合DSM-Ⅳ双相抑郁诊断标准的患者随机分为喹硫平组与碳酸锂组,在基线和治疗期每周采用HAMD-17、HAMA、MADRS、YMRS、CGI-I和TESS进行评定。结果以MADRS评分,喹硫平组和碳酸锂组有效率分别为86.86%、82.45%,痊愈率分别为54.35%、52.48%,两组的疗效差异无统计学意义（P〉0.5）;两组在治疗终末HAMD-17、HAMA、MADRS、CGI-I的减分率差异无统计学意义（P〉0.5）;HAMA减分值比较,喹硫平组起效快于碳酸锂组,差异具有统计学意义（P〈0.01）。两组患者均有良好的耐受性。结论喹硫平单药可有效治疗双相抑郁,尤其适用于伴焦虑的双相抑郁。     

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.     

Bipolar I and II disorder residual symptoms: Oxcarbazepine and carbamazepine as add-on treatment to lithium in a double-blind,randomized trial

Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC (n = 26) or CBZ (n = 26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint (p < 0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 (p < 0.05) and from baseline to week 8 (p < 0.001), except YMRS (p < 0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings.     

Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression

BACKGROUND: Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination. METHOD: In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records. RESULTS: Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.     

The impact of glycogen synthase kinase 3β gene on psychotic mania in bipolar disorder patients

Objective

The aim of this study was to examine the relationships between glycogen synthase 3β gene polymorphisms and bipolar I disorder, manic in a Korean sample.

Methods

Patients with bipolar disorder (n = 118) and a control group (n = 158) were assessed by genotyping for GSK3β single nucleotide polymorphisms (SNPs) − 1727A/T and − 50C/T. The patients were divided into two groups according to the presence of psychotic symptoms (psychotic mania, n = 92; non-psychotic mania, n = 26) and also divided based on gender and age of onset. The severity of symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).

Results

There were no significant differences in the genotype distributions or allelic frequencies of GSK3β polymorphisms and gender between patients with bipolar disorder and a normal control group. According to haplotype analysis, there was no association between these two groups. However, analysis of the age of onset of bipolar disorder revealed significant differences in genotype and allele distributions among the patients. Patients who were homozygous for the wild-type variant (TT) had an older age of onset than carriers of the mutant allele (A/A: 27.4 ± 9.1; A/T: 30.1 ± 11.8; T/T: 42.3 ± 19.9; p = 0.034). We detected differences in allele frequencies of the GSK3β − 1727A/T polymorphism between the psychotic mania group and the non-psychotic mania group.

Conclusion

This study suggests that GSK3β polymorphisms are not associated with bipolar disorder. However, the GSK3β SNP − 1727A/T is associated with age of onset and presence of psychotic symptoms in bipolar disorder.     

Electroconvulsive therapy in medication-nonresponsive patients with mixed mania and bipolar depression

BACKGROUND: The aim of this study was to investigate the effectiveness of electroconvulsive therapy (ECT) in medication-nonresponsive patients with mixed mania and bipolar depression. METHOD: Forty-one patients with mixed mania (DSM-IV diagnosis of bipolar I disorder, most recent episode mixed) and 23 patients with bipolar depression (DSM-IV diagnosis of bipolar I disorder, most recent episode depressed) consecutively assigned to ECT treatment were included in this study. Subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions-Severity of Illness scale (CGI-S). Assessments were carried out the day before starting ECT, 48 hours after completion of the third session (T1), and a week after the last session of ECT (T2). RESULTS: Both groups received an equal number of ECT sessions (mean +/- SD = 7.2 +/- 1.7 vs. 7.3 +/- 1.6). In both groups, within-group comparisons showed that there was a significant reduction in CGI-S score (mixed mania, p <.0001 at T1 and T2; bipolar depression, p < .01 at T1, p < .0001 at T2), MADRS total score (both groups, p < .0001 at T1 and T2), BPRS total score (mixed mania, p < .0001 at T1 and T2; bipolar depression, p < .001 at T1, p < .0001 at T2), and BPRS activation factor score (mixed mania, p < .0001 at T1 and T2; bipolar depression, NS at T1, p < .01 at T2). Between-group comparisons revealed that patients with mixed mania showed significantly greater decrease in MADRS score (p < .001) and a greater proportion of responders (CGI-S) than patients with bipolar depression at endpoint (56% [N = 23] vs. 26% [N = 6], p = .02). Patients with mixed mania showed a greater reduction in suicidality, as measured by MADRS score, than patients with bipolar depression (p < .02). CONCLUSION: In our study, ECT was associated with a substantial reduction in symptomatology, in both patients with mixed mania and those with bipolar depression. However, the mixed mania group exhibited a more rapid and marked response as well as a greater reduction in suicidal ideation. Response to ECT was not influenced by the presence of delusions.     

抗精神病药对躁狂症的治疗作用：利培酮治疗躁狂症对照观察

目的：了解利培酮对躁狂症患者的疗效及不良反应。方法：对90例躁狂症患者随机分为单用利培酮组30例,利培酮合并碳酸锂组30例及氯氮平合并碳酸锂组30例,在治疗前及治疗第1、2、4、6、8周末分别评定Young氏躁狂量表（YMRS）、阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）,以了解疗效及不良反应。结果：单用利培酮组、利培酮合并碳酸锂组及氯氮平合并碳酸锂组治疗第2、4、6、8周末YMRS、PANSS总分均显著下降（P〈0.01）,但3组间比较差异无显著性（P〉0.05）。治疗第4、6、8周末TESS总分3组间比较差异有显著性（P〈0.01）。利培酮合并碳酸锂组及氯氮平合并碳酸锂组不良反应较单用利培酮组明显增多,尤其是氯氮平合并碳酸锂组更甚。结论：单用利培酮治疗躁狂症有效,而且不良反应更小。