Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression

BACKGROUND: Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. OBJECTIVE: To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. DESIGN: Double-blind, 8-week, randomized controlled trial. SETTING: Eighty-four sites (inpatient and outpatient) in 13 countries.Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20.Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86). MAIN OUTCOME MEASURE: Changes in MADRS total scores using mixed-effects model repeated-measures analyses. RESULTS: During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group (P<.001 for all). The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8. At week 8, MADRS total scores were lower than at baseline by 11.9, 15.0, and 18.5 points in the placebo, olanzapine, and olanzapine-fluoxetine groups, respectively. Remission criteria were met by 24.5% (87/355) of the placebo group, 32.8% (115/351) of the olanzapine group, and 48.8% (40/82) of the olanzapine-fluoxetine group. Treatment-emergent mania (Young Mania Rating Scale score <15 at baseline and > or =15 subsequently) did not differ among groups (placebo, 6.7% [23/345]; olanzapine, 5.7% [19/335]; and olanzapine-fluoxetine, 6.4% [5/78]). Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea. CONCLUSIONS: Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.     

A 52-week, open-label continuation study of lamotrigine in the treatment of bipolar depression

BACKGROUND: Lamotrigine has demonstrated efficacy for the acute treatment of depression in bipolar I patients in a placebo-controlled, monotherapy study. We describe the results of a 52-week, open-label continuation of that trial. METHOD: Patients meeting DSM-IV criteria for bipolar I disorder with a current major depressive episode who completed a 7-week, double-blind study of bipolar depression were offered 1 year of open-label lamotrigine therapy (flexible doses of 100-500 mg/day) in a continuation study. To maintain the acute study blind, the first 3 weeks of the continuation study remained blinded while patients previously randomly assigned to placebo were titrated to a lamotrigine dose of 50 mg/day. Patients who had been randomly assigned to lamotrigine continued at their fixed doses. Beginning at week 4, all patients received open-label lamotrigine for up to 49 additional weeks. Concomitant psychotropic medications were permitted during the open-label phase. Effectiveness (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions-Improvement scale) and safety assessments were administered at weeks 4, 12, 24, 36, and 52. The study was conducted from June 1996 to December 1998. RESULTS: Of 135 patients completing the acute study, 124 (92%) entered the continuation study: 77 had received lamotrigine and 47 had received placebo in the acute study. The mean duration of lamotrigine exposure was 10.4 months, with a mean modal dose of 187 mg/day. Sixty-nine patients (56%) completed 1 year of treatment. Significant and sustained improvement from baseline was seen in mean observed MADRS scores (p <.05). The proportion of patients achieving remission (MADRS score < or = 11) by week 4 of the study was 81.4%, and episodes of mania/hypomania occurred less frequently than in the preceding year. Headache was the most common drug-related adverse event. CONCLUSION: During 1 year of open-label therapy with lamotrigine as adjunctive therapy or monotherapy, bipolar I patients experienced sustained improvement in depressive symptoms without evidence of mood destabilization.     

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.     

A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease

BACKGROUND: This study is an extension of a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate to severe Alzheimer disease. OBJECTIVE: To evaluate long-term memantine treatment in moderate to severe Alzheimer disease. DESIGN, SETTING, AND PATIENTS: Open-label, 24-week extension trial. Raters remained blind to the patients' initial study treatment. Patients (n = 175) were enrolled from the previous double-blind study in an outpatient setting. INTERVENTION: Twenty mg of memantine was given daily. MAIN OUTCOME MEASURES: Efficacy assessments from the double-blind study were continued and safety parameters were monitored. RESULTS: Patients who switched to memantine treatment from their previous placebo therapy experienced a significant benefit in all main efficacy assessments (functional, global, and cognitive) relative to their mean rate of decline with placebo treatment during the double-blind period (P<.05). The completion rate for the extension phase of the study was high (78%) and the favorable adverse event profile for memantine therapy was similar to that seen in the double-blind study. CONCLUSION: These results extend previous findings that demonstrated the efficacy and safety of memantine in the treatment of patients with moderate to severe Alzheimer disease.     

An open-label study of lamotrigine adjunct or monotherapy for the treatment of adolescents with bipolar depression

OBJECTIVE: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. METHOD: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages 12-17 years (mean age 15.8; 7 boys, 13 girls) with diagnoses of bipolar disorder I, II, or not otherwise specified, who were experiencing a depressive episode. Lamotrigine was begun at 12.5 to 25 mg/day. Primary response criteria was a 1 or a 2 on the Clinical Global Impression-Improvement at week 8. A secondary criterion was at least a 50% decrease in Children's Depression Rating Scale-Revised scores. RESULTS: Nineteen subjects completed the trial. The mean final dose was 131.6 mg/day. Seven subjects were taking other psychotropic medications. Sixteen subjects (84%) responded by primary criteria, and 12 (63%) responded to our secondary criteria. Eleven subjects (58%) were considered in remission at week 8. Young Mania Rating Scale and Overt Aggression Scale-Modified scores also decreased significantly during the trial. There was no significant weight change, rash, or other adverse effects during the trial. CONCLUSIONS: Adolescents with bipolar depression appeared to respond to lamotrigine treatment, whether as adjunctive therapy or monotherapy, with decreases in depression, mania, and aggression. Larger, placebo-controlled studies of lamotrigine are needed in this population.     

A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression

OBJECTIVE: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine. METHOD: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004. RESULTS: Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > or = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < or = .001). CONCLUSIONS: Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size.     

Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study

BACKGROUND: The olanzapine/fluoxetine combination has demonstrated effectiveness in treatment-resistant depression (TRD). Although this combination is being used by prescribers, this is the first study to examine long-term use. Long-term efficacy and safety were therefore investigated in a group of patients with major depressive disorder (MDD) with and without TRD. METHOD: 560 patients who met DSM-IV diagnostic criteria for MDD were enrolled in this 76-week, open-label study (Feb. 2000-July 2002). The Montgomery-Asberg Depression Rating Scale (MADRS) total score was the primary efficacy measure. Safety was assessed via adverse events, vital signs, laboratory analytes, electrocardiography, and extrapyramidal symptom measures. RESULTS: MADRS mean total scores decreased 7 points from baseline (31.6 [N = 552]) at 1/2 week of treatment, 11 points at 1 week of treatment, and 18 points at 8 weeks of treatment. This effect was maintained to endpoint with a mean decrease of 22 points at 76 weeks. Response and remission rates for the total sample were high (62% and 56%, respectively), and the relapse rate was low (15%). Response, remission, and relapse rates for TRD patients (N = 145) were 53%, 44%, and 25%, respectively. The most frequently reported adverse events were somnolence, weight gain, dry mouth, increased appetite, and headache. At endpoint, there were no clinically meaningful changes in vital signs, laboratory analytes, or electrocardiography. There were no significant increases on any measure of extrapyramidal symptoms. CONCLUSIONS: The olanzapine/fluoxetine combination showed rapid, robust, and sustained improvement in depressive symptoms in patients with MDD, including patients with TRD. The long-term safety profile of the combination was similar to that of its component monotherapies.     

Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression

OBJECTIVES: The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination. METHODS: Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis. RESULTS: Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001). CONCLUSIONS: Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.     

A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients

OBJECTIVE: The purpose of this study was to investigate the effectiveness of zonisamide in the treatment of bipolar depression. METHOD: Ten patients with DSM-IV bipolar disorder, depressed phase, who had either not tolerated or not responded to previous treatments were given zonisamide in this add-on open-label study. Zonisamide treatment was started at 100 mg/day and increased by 100 mg every 2 weeks to a maximum of 300 mg/day in divided doses (b.i.d. or t.i.d.). Subjects underwent weekly visits at which they were administered the 17-item Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale (CGI). Every 2 weeks, subjects also underwent laboratory tests, a urine examination, and a verbal memory test. Outcome measures were analyzed with repeated-measures analysis of variance. RESULTS: Eight subjects completed all 8 weeks of the study. Two subjects completed more than 4 weeks of the study, and their data were analyzed using the last observation carried forward. Bipolar depression subjects had a significant reduction in HAM-D scores (p < .001) and in CGI-Improvement (CGI-I) scores (p < .001). Five of 8 subjects who completed all 8 weeks of the study had more than a 50% decrease in HAM-D scores and were rated much improved on the CGI-I at the end of 8 weeks of treatment. There was no significant drug effect on YMRS scores, weight, or verbal memory. CONCLUSION: Zonisamide may be a useful drug in the treatment of bipolar depression. Further controlled clinical trials are needed.     

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.     

Risperidone in the treatment of mixed state bipolar patients: Results from a 24-week, multicenter, open-label study in Korea

Aims:  The goal of the present study was to evaluate the efficacy of risperidone combined with mood stabilizers for treating bipolar mixed state.
Methods:  The present study was a 24-week, open-label, combination, prospective investigation of the efficacy of risperidone in combination with mood stabilizers. Risperidone (1–6 mg/day) was given in combination with mood stabilizers in flexible doses according to clinical response and tolerability for 114 patients in mixed or manic episode.
Results:  Forty-four patients met our criteria for mixed state bipolar disorder and 70 met the criteria for pure mania. Mean age for the subjects was 39.0 ± 11.0 years and 55.3% were female. The combination of risperidone with mood stabilizers significantly improved the scores on the Young Mania Rating Scale (YMRS), 17-item Hamilton Rating Scale for Depression (HAMD), 18-item Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and Clinical Global Impression Scale for use in bipolar illness Severity (CGI-BP) at 24 weeks ( P  < 0.0001). Analysis of the YMRS, BPRS, GAS, and CGI-BP scores showed significant improvement in both the manic and mixed groups. The rate of response in YMRS scores was 84.2% ( n  = 96) and the rate of YMRS remission was 77.2% ( n  = 88) at week 24 in the total population. Seventy-four patients met both YMRS ≤ 12 and HAMD ≤ 7 at week 24 (64.9%). Risperidone was well tolerated, and adverse events were mostly mild.
Conclusion:  The combination of risperidone with mood stabilizers was an effective and safe treatment for manic symptoms and coexisting depressive symptoms of bipolar disorder.     

Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study

BACKGROUND: Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials. METHOD: In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension. RESULTS: The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%). CONCLUSION: During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.     

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

OBJECTIVE: To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania. METHODS: This was an eight-week, open-label, prospective study of ziprasidone monotherapy (57.3 +/- 33.9 mg/day) in 21 bipolar youth [manic, mixed, or bipolar not otherwise specified (NOS); 6-17 years old]. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. RESULTS: Fourteen of the 21 youth (67%) completed the study. Ziprasidone treatment was associated with clinically and statistically significant improvement in mean YMRS scores (-10.8 +/- 8.4, p < 0.0001) and 57% had a CGI-I 相似文献   

艾司西酞普兰单用与合用氨磺必利治疗重性抑郁症的疗效和安全性

目的 探讨氨磺必利合用艾司西酞普兰治疗重性抑郁症的有效性和安全性.方法 80例重性抑郁症患者随机分为艾司西酞普兰组(对照组)和艾司西酞普兰合用氨磺必利组(研究组)各40例,疗程8周.于治疗前和治疗后第1、2、4、8周末采用汉密尔顿抑郁量表(HAMD)评定疗效,采用不良事件和实验室检查评价安全性.结果 两组治疗后第8周末缓解率分别为57.9％和64.9％,差异无统计学意义(x2=0.384,P＞0.05).两组HAMD评分治疗后均较治疗前显著降低,差异有统计学意义(P＜0.05).研究组在治疗后第1、2周末HAMD评分显著低于对照组,差异有统计学意义(t=2.91,2.72;P＜0.05).两组不良反应均轻微,差异无统计学意义(P＞0.05).结论 艾司西酞普兰合用氨磺必利治疗重性抑郁症起效更快.     

An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression.

BACKGROUND: Preclinical and clinical evidence indicate that the glutamatergic system might play a role in the pathophysiology of mood disorders. This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in bipolar depression. METHODS: This was an 8-week add-on study of riluzole in combination with lithium in acutely depressed bipolar patients aged 18 years and older. After open treatment with lithium for a minimum period of 4 weeks, subjects who continued to have a Montgomery-Asberg Depression Rating Scale (MADRS) score of >/=20 received riluzole (50-200 mg/day) for 8 weeks. RESULTS: Fourteen bipolar depressed patients entered the study. The linear mixed models for total MADRS score showed a significant treatment effect. No switch into hypomania or mania was observed. Overall, riluzole was well tolerated. CONCLUSIONS: Although preliminary, these results suggest that riluzole might indeed have antidepressant efficacy in subjects with bipolar depression.     

奥氮平联合氟西汀治疗双相抑郁的对照研究

目的探讨奥氮平联合氟西汀治疗双相抑郁的疗效及安全性。方法将符合CCMD-3中国精神障碍分类和诊断标准（第三版）的60例双相障碍抑郁患者随机分为两组,每组30例。研究组用奥氮平联合氟西汀,对照组用帕罗西汀联合碳酸锂,分别治疗8周。以汉密尔顿抑郁量表（HAMD）,汉密尔顿焦虑量表（HA-MA）,治疗时出现的症状量表（TESS）在治疗前和治疗后第2、8周末评价疗效和安全性,在第2、8周末及4、4、需要时用Bech-Rafaelse躁狂量表（BRMS）评定转躁情况。结果两组治疗后HAMD、HAMA评分均较治疗前显著降低（P〈0.01）,研究组和对照组显效率分别为66.67%和64.29%,无显著性差异（P〉0.05）。研究组不良反应为嗜睡、头昏和昏厥、便秘、鼻塞、体重增加等。对照组则为兴奋或激越、肝功能异常、震颤、恶心呕吐、食欲减退或厌食、头痛等,两组差异有显著性（P〈0.05）。结论奥氮平联合氟西汀可有效治疗双相抑郁,不良反应较少,依从性好,并能减少诱发躁狂的风险。     

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 preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapine-fluoxetine combination in women with borderline personality disorder

BACKGROUND: The intent of this study was to compare the efficacy and safety of fluoxetine, olanzapine, or the olanzapine-fluoxetine combination (OFC) in the treatment of women meeting criteria for borderline personality disorder (without concurrent major depressive disorder). METHOD: We conducted a randomized double-blind study of these agents in female subjects meeting Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-IV criteria for borderline personality disorder. Treatment duration was 8 weeks. Outcome measures were clinician-rated scales measuring depression (the Montgomery-Asberg Depression Rating Scale) and impulsive aggression (the Modified Overt Aggression Scale). Data were collected from August 2001 through March 2003. RESULTS: Fourteen subjects were randomized to fluoxetine; 16, to olanzapine; and 15, to OFC. Forty-two of these subjects (93.3%) completed all 8 weeks of the trial. Using random-effects regression modeling of panel data of change-from-baseline scores and controlling for time, olanzapine monotherapy and OFC were associated with a significantly greater rate of improvement over time than fluoxetine on both outcome measures. However, it should be noted that fluoxetine treatment led to a substantial reduction in impulsive aggression and severity of depression. Weight gain was relatively modest in all 3 groups but significantly greater in the olanzapine-treated group than in the groups treated with fluoxetine alone or OFC. CONCLUSION: All 3 compounds studied appear to be safe and effective agents in the treatment of women with borderline personality disorder, significantly ameliorating the chronic dysphoria and impulsive aggression common among borderline patients. However, olanzapine monotherapy and OFC seem to be superior to fluoxetine monotherapy in treating both of these dimensions of borderline psychopathology.