Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P 相似文献   

A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder

We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.     

Efficacy of olanzapine monotherapy for treatment of bipolar I depression: a randomized,double-blind,placebo controlled study

Rationale and objective

Depression symptoms are now recognized to be the predominant cause of disability for bipolar disorder (BD) patients. The treatment strategies for the depressed phase of BD remain more anecdotal than data-based. Olanzapine has been investigated as an alternative to antidepressants and a mood stabilizer for acute bipolar depression. The purpose of this study was to assess the efficacy of olanzapine monotherapy for bipolar I depression.

Method

Sixty-eight patients with bipolar I depression were randomly assigned to treatment with olanzapine (mean final dose 14.4 mg/day) (n?=?34) or placebo (n?=?34) in a double-blind parallel-group study design. Planned assessments included Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness scale (CGI-S), Clinical Global Impressions-Improvement scale (CGI-I), Hamilton Depression scale (HAMD), Hamilton Anxiety scale (HAMA), and Treatment Emergent Symptom Scale (TESS).

Results

Of the 68 patients who were randomly assigned, 57 (83.8 %) completed treatments. Improvements in MADRS total score, CGI-S, CGI-I, and HAMD in the olanzapine group were significantly greater relative to those in the placebo group during the 8-week follow-up period (p?<?0.001, p?=?0.0017, p?=?0.007, and p?<?0.001, respectively). Rates of categorical treatment response and remission in the olanzapine group (50.0 % and 35.3 %, respectively) were significantly higher than those in the placebo group (20.6 %, p?=?0.011 and 11.8 %, p?=?0.022, respectively). At the 8-week treatment, the mean weight and the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased significantly in the olanzapine group (p?=?0.037, p?=?0.029, p?=?0.030, and p?=?0.028, respectively).

Conclusions

Olanzapine is effective in the treatment of bipolar I depression but is associated with significant metabolic side effects.     

A double-blind, placebo-controlled, randomized pilot study comparing quetiapine with placebo, associated to naltrexone, in the treatment of alcohol-dependent patients

The objective of this study was to determine whether quetiapine plus naltrexone is more effective than naltrexone alone for the treatment of alcohol-dependent patients. This was a double-blind, randomized clinical trial where eligible alcohol-dependent patients were randomized to receive naltrexone (50mg/day) plus quetiapine (25-200mg/day) or naltrexone (50mg/day) plus placebo for 12 weeks, and afterwards patients received naltrexone alone during 4 additional weeks. The primary efficacy measures were percent days abstinent, drinks per drinking day, and the relapse rate. Sixty-two patients received a single-blind treatment with placebo plus naltrexone, and they were thereafter randomly assigned to quetiapine plus naltrexone (n=30) or placebo plus naltrexone (n=32). Eleven (36.7%) patients in the quetiapine-treated group and 4 (12.5%) patients in the placebo-treated group withdrew before they completed 12 weeks of treatment. There were no statistically significant differences for any primary drinking outcomes between treatment groups. Both regimens were well tolerated. This study failed to demonstrate any additional benefit from the combination of quetiapine and naltrexone compared to naltrexone alone on drinking outcomes.     

拉莫三嗪与喹硫平治疗双相抑郁的对照研究

目的比较拉莫三嗪(利必通)和喹硫平(思瑞康)治疗双相抑郁的疗效及安全性。方法对71例符合CCMD-3诊断双相障碍(目前为抑郁发作)的患者按随机、平行、对照的方法分为拉莫三嗪组和喹硫平组,观察8周,分别于第0、2、4、6、8周末用HAMD、CGI评价疗效,于第2、4、6、8周末用TESS评定不良反应,于第4、8周末用BRMS评定躁狂症状。结果拉莫三嗪组的痊愈率34.21%,有效率65.79%,喹硫平组的痊愈率39.39%,有效率69.70%。两组疗效比较无显著性差异(P>0.05),两组不良反应发生率相当。结论拉莫三嗪和喹硫平均可首选用于双相抑郁治疗,且安全性、不良反应相当。     

Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies

Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).     

Impact of diagnosis and treatment of hypertension on quality of life: a double-blind, randomized, placebo-controlled, cross-over study of betaxolol.

In an experimental study, 150 general practitioners studied 468 apparently healthy subjects whose blood pressure (BP) level was unknown or had not been measured for 1 year. The study lasted for 10 weeks. If BP was greater than 95 mm Hg on the first two visits, subjects were randomized into two experimental groups for 8 weeks, with cross-over from betaxolol to placebo and vice versa after 4 weeks. Quality of life was measured at visits 1, 3 (2 weeks), 5 (6 weeks), and 7 (10 weeks) in five ways: well-being, physical state, sexual functioning, sleep, and cognitive acuity. BP level appeared to be effectively controlled by betaxolol as compared with placebo. The results show that no effects on quality of life could be detected by labeling subjects as hypertensives. Equally, almost no effects of active treatment could be established. Learning effects on the two cognitive acuity measurements used were attenuated by betaxolol, however. Apparently, in a carefully controlled study, the effects of increased medical attention and care outweight the potentially negative effects of labeling and treatment.     

A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment.     

A randomized,placebo-controlled,double-blind trial of sertraline for postpartum depression

Rationale

Postpartum depression (PMD) occurs in roughly 10 % of postpartum women and negatively impacts the mother and her offspring, but there are few placebo-controlled studies of antidepressant treatment in this population.

Objective

The objective was this study is to compare the selective serotonin reuptake inhibitor (SSRI) sertraline to placebo for treating PMD.

Methods

This was a single-center, 6-week, randomized double-blind placebo-controlled trial of sertraline with a 1-week placebo lead-in. The participants (n?=?38) were women with depression onset within 3 months of delivery; a subset (n?=?27) met strict DSM-IV criteria for PMD (onset within 4 weeks of delivery). The participants were prescribed sertraline 50 mg or placebo daily to a maximum of 200 mg/day. Primary outcome variables were the Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impressions (CGI) scores, which were used to determine the rates of response and remission.

Results

Sertraline produced a significantly greater response rate (59 %) than placebo (26 %) and a more than twofold increased remission rate (53 % vs. 21 %). Mixed models did not reveal significant group by time effects, although in the subset of women who met the DSM-IV criteria, there was a statistically significant group by time effect for the HAM-D, Hamilton Anxiety Rating Scale (HAM-A), and CGI.

Conclusions

Women with PMD are more likely to have a remission of their depression with sertraline treatment, a finding that is more pronounced in women who have onset of depression within 4 weeks of childbirth. These data support the continued use of 4 weeks for the DSM-5 postpartum onset specifier for major depressive disorder.     

Duloxetine-bupropion combination for treatment-resistant atypical depression: A double-blind,randomized, placebo-controlled trial

The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the “+placebo” and “+bupropion” groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.     

Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study

Anger and aggression are typical in borderline patients. The goal of this study was to compare the efficacy of lamotrigine versus placebo in the treatment of aggression in women meeting the criteria for borderline personality disorder (BPD). We conducted a randomized, double-blind, placebo-controlled study of lamotrigine in 24 female subjects meeting Structured Clinical Interview for DSM-IV (SCID) criteria for BPD. The subjects were randomly assigned in a 2: 1 manner ratio to lamotrigine (n = 18) or placebo (n = 9). Treatment duration was 8 weeks. Primary outcome measures were self-reported changes on the anger scales of the Trait Anger Expression Inventory (STAXI). In comparison with the placebo group, and according to the intention-to-treat principle, highly significant (p < 0.01) changes on four STAXI scales (State-Anger, Trait-Anger, Anger-Out, Anger-Control) were observed in those subjects treated with lamotrigine after 8 weeks. The only exception (p < 0.05) was found on the Anger-In scale, where a difference of only 8.5% (p < 0.2) was found. All the patients tolerated lamotrigine relatively well. Lamotrigine appears to be a safe and effective agent in the treatment of anger in women with criteria-defined BPD as defined by SCID criteria. It did not produce any clinically significant effect on body weight.     

Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study

Current guidelines for the treatment of bipolar type II (BP II) major depressive episode (MDE) recommend using either mood stabilizer monotherapy or the combination of a mood stabilizer with a selective serotonin reuptake inhibitor (SSRI). These guidelines are the result of concern over SSRI-induced manic switch episodes. We previously showed that fluoxetine monotherapy may be effective as an initial treatment for BP II and BP NOS MDE with a low manic switch rate. We now present the results of a double-blind, placebo-substitution continuation study of fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their MDE. This was a two-phase study. In study phase I, patients received open-label fluoxetine monotherapy 20 mg daily for up to 8 weeks. Responders with a final 17-item Hamilton Rating Scale for Depression (HAM-D) score < or =9 were enrolled into study phase II which consisted of double-blind, placebo-substitution continuation therapy with fluoxetine 20 mg daily for up to 6 months. Outcome measures included the 17-item HAM-D and Young Mania Rating (YMR) scales. Changes in YMR scores were assessed using generalized estimating equation analysis. Relapse was assessed using Kaplan-Meier survival analysis and Fisher's exact test. In study phase II, 43% of fluoxetine-treated patients and 100% of placebo-treated patients relapsed during continuation therapy (P=0.08). The mean increase in YMR score in study phase II was slightly higher in the fluoxetine-treated patients (3.0+/-1.8) versus placebo-treated patients (0.2+/-0.4) (P=0.01). However, this difference was not clinically meaningful. No hypomanic switch episodes were observed during study phase II. Despite the limited sample size resulting in insufficient power to detect statistical significance in relapse rates or change in YMR scores between treatment conditions, these preliminary data appear to support previous observations demonstrating that initial and continuation fluoxetine monotherapy may be safe and effective for some patients with BP II or BP NOS MDE with a low manic switch rate. Larger-scale studies are needed to confirm these findings.     

Evaluation of the effect of paliperidone extended release and quetiapine on corrected QT intervals: a randomized, double-blind, placebo-controlled study

The effect of two atypical antipsychotics on QTc intervals (heart rate-corrected QT interval) was evaluated. Patients (N=109) with schizophrenia (79%) or schizoaffective disorder (21%) were randomly assigned in 2 : 2 : 1 ratio to paliperidone extended release (ER), quetiapine, or placebo. Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day. Least-squares mean change from baseline in population-specific linear-derived correction method from baseline to days 6-7 at individual tmax was 5.1 ms less [90% confidence interval: -9.2 to -0.9] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day. On the basis of a prespecified 10-ms noninferiority margin, paliperidone ER was thus declared noninferior to quetiapine (primary analysis). Mean change in population-specific linear-derived correction method from baseline to days 11-12 at individual tmax was 2.3 ms less (90% confidence interval: -6.8 to 2.3) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day. Treatment-emergent adverse events occurred in 36 (82%) patients treated with paliperidone ER, 41 (95%) patients treated with quetiapine, and 14 (64%) patients treated with placebo. No adverse events of a proarrhythmic nature were noted. The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day (maximum recommended dose), paliperidone ER 18 mg/day (supratherapeutic dose), and quetiapine 800 mg/day.     

Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: A randomized,double-blind,placebo-controlled trial

Controversy exists as to whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression. We conducted a single-center, randomized, double-blind, placebo-controlled, multi-arm, parallel-group trial, comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression. Eighty-one mild-to-moderately depressed outpatients were randomly assigned to receive either 1 g/d of EPA or DHA or placebo (coconut oil) for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS) final score in the modified intention-to-treat population, which comprised of all randomized patients with at least 1 post-randomization observation (n=62; 61.3% female; mean age 35.1±1.2 years). Allocated treatments were well tolerated. Although there was no significant difference between groups at baseline, patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA (p<0.001) or placebo (p=0.002) groups. Furthermore, response to treatment (defined as a ≥50% decrease from the baseline HDRS score) was only observed in 6 patients receiving EPA, while no one in any of DHA or placebo groups responded to treatment. Overall, these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression. However, further, randomized controlled trials are needed to support these findings.     

Mirtazapine treatment of social phobia in women: a randomized, double-blind, placebo-controlled study

Social phobia is an anxiety disorder characterized by extreme fear and phobic avoidance of social and performance situations and by a relatively poor health-related quality of life. The goal of this study was to compare the efficacy of mirtazapine versus placebo in the treatment of patients with social phobia. In 2004, we conducted a randomized, double-blind, placebo-controlled study of mirtazapine in 66 female subjects from the general population meeting the criteria for social phobia. The subjects were randomly assigned in a 1:1 manner to mirtazapine (n = 33) or placebo (n = 33). The treatment lasted 10 weeks. Seven patients dropped out. Primary outcome measures were self-reported changes on the Social Phobia Inventory, Liebowitz Social Anxiety Scale, and Health Survey (SF-36). In comparison with the placebo group and according to the intent-to-treat principle, significant differences on the Social Phobia Inventory and Liebowitz Social Anxiety Scale scales (all P < 0.001), as well as on most (5 from 8) scales of SF-36 (all P < 0.001), were observed in the mirtazapine-treated subjects. All patients tolerated mirtazapine relatively well. Mirtazapine appears to be an effective agent in the treatment of social phobia in women and in the improvement of their health-related quality of life.     

Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study

We tested the efficacy of bupropion in the treatment of persons with pathological gambling (PG). Nondepressed, healthy subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PG were randomly assigned to placebo or flexibly dosed bupropion in a 12-week double-blind trial. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale modified for PG, the Gambling Severity Assessment Scale, the Clinical Global Impression Improvement and Severity Scales, the Global Assessment Scale, the Timeline Follow Back, the Attention-Deficit/Hyperactivity Disorder Rating Scale, and the Sheehan Disability Scale. Thirty-nine subjects (28 men, 11 women) were randomized to bupropion (n = 18) or placebo (n = 21). The 2 groups were similar on demographic and clinical measures. There were few differences between the treatment groups on any primary or secondary outcome measure, although subjects in each cell experienced significant improvement. Of subjects with at least 1 postrandomization visit, 35.7% of bupropion and 47.1% of placebo recipients experienced "much" or "very much" improvement on the Clinical Global Impression Improvement Scale. The trial was complicated by a high noncompletion rate (43.6%). Bupropion was well tolerated. Bupropion and placebo recipients did equally well in a short-term trial, with improvement seen as early as the first week of treatment. The high placebo response rate and the high noncompletion rate each reflect the challenge inherent in treating persons with PG.     

拉米夫定治疗慢性乙型肝炎的多中心、随机双盲、安慰剂对照研究

目的：研究拉米夫定对血清乙型肝炎病毒＿脱氧核糖核酸（ＨＢＶ＿ＤＮＡ）阳性的慢性乙型肝炎病毒感染病人的疗效和安全性。方法：４２９例病人,随机分成拉米夫定治疗组（３２２例）和安慰剂对照组（１０７例）。治疗组每日口服拉米夫定１００ｍｇ,对照组服用外形相同的安慰剂每日１片,共１２ｗｋ。结果：治疗组累计９２．２％病人血清ＨＢＶ＿ＤＮＡ阴转（低于１．６ｎｇ／Ｌ）,最终持续阴转率为７８．５％。对照组ＨＢＶ＿ＤＮＡ累计阴转率为１４．１％,最终阴转率为１１％。２组疗效比较Ｐ＜０．０１。治疗前丙氨酸转氨酶（ＡＬＴ）增高的病人,１２ｗｋ时治疗组的ＡＬＴ复常率为６０．３％,对照组为２７％,Ｐ＜０．０１。２组ＨＢｅＡｇ／抗ＨＢｅ的血清转换率差别无显著意义（Ｐ＞０．０５）。２组的不良反应发生率比较,差别无显著意义（Ｐ＞０．０５）。结论：拉米夫定能明显降低血清ＨＢＶ＿ＤＮＡ水平,促使ＡＬＴ恢复正常,不良反应轻,耐受性好。