艾司西酞普兰治疗抑郁症伴焦虑的疗效分析

目的评价国产艾司西酞普兰片治疗抑郁症伴焦虑的疗效及安全性。方法本研究为6周的多中心开放性研究,共入组符合CCMD-3诊断标准的抑郁症(同时HAMD≥17分、HAMA≥14分)患者173例,服用国产艾司西酞普兰片的剂量为10mg-20mg/d,分别在治疗前及第1、2、4、6周末以汉密尔顿抑郁量表17项(HAMD)、汉密尔顿焦虑量表(HAMA)和临床总体印象量表CGI(包括病情严重程度评分CGI-SI、疗效评分CGI-GI)评定疗效,以不良事件记录表、体格检查、实验室检查评估用药安全性。结果共169例患者完成研究,经6周治疗后显示,HAMD、HAMA、CGI-SI评分呈现一致的减分趋势,各时点HAMD-17、HAMA、CGI-SI的总分与治疗前比较,差异均有显著性(P<0.05),总体有效率为81.1%、痊愈率是63.9%。不良反应发生率为10.06%,一般可以耐受。结论国产艾司西酞普兰片治疗抗抑郁及焦虑作用确切,可用于治疗抑郁症伴焦虑障碍。     

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.     

Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial.

OBJECTIVE: Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD). METHODS: In this randomized, double-blind trial, patients age > or =18 meeting DSM-IV criteria for MDD were randomized to placebo (N=99), duloxetine 80 mg/day (N=93), duloxetine 120 mg/day (N=103), or paroxetine 20 mg/day (N=97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD(17)) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a > or =30% reduction from baseline in the HAMD(17) total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment. RESULTS: More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P<0.05) in the HAMD(17) total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P=0.089) on mean change on the HAMD(17). Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD(17) mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases. CONCLUSIONS: The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.     

Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder

OBJECTIVE: To evaluate the efficacy and tolerability of gepirone extended-release (ER) tablets in patients with major depressive disorder (MDD) and high ratings of anxiety (anxious depression). METHOD: This subgroup analysis was derived from an 8-week, double-blind, placebo-controlled study of gepirone ER in patients with MDD. Male and female patients 18 to 69 years of age who met DSM-IV criteria for MDD and had high ratings of anxiety (Hamilton Rating Scale for Depression [HAM-D-17] total score > or = 20 and HAM-D-17 factor I [anxiety/somatization] score > 6) were included in this subgroup analysis. Eligible patients with anxious depression were randomly assigned to receive either placebo or gepirone ER, 20 mg to 80 mg daily. Patient assessments were performed at weeks 1, 2, 3, 4, 6, and 8. Treatment efficacy was evaluated by mean HAM-D-17 total scores and mean changes from baseline in (1) HAM-D-17 total scores, (2) HAM-D-17 factor I (anxiety/somatization) scores, and (3) HAM-D-17 item 12 (anxiety, psychic) scores. All statistical tests were 2-sided and considered statistically significant if the p value was <.05. Between-group comparisons were analyzed using least-squares analysis of variance on the change from baseline at each visit with the last observation carried forward (LOCF). The Cochran-Mantel-Haenszel test adjusting for center was also performed on the percentage of patients in each treatment group at each visit (LOCF) who met the response criterion on the HAM-D-17 (> or = 50% decrease from baseline) or remission criterion (HAM-D-17 total score < or = 7). RESULTS: Gepirone ER-treated patients (N = 58) experienced a statistically significant (p <.05) reduction in mean HAM-D-17 total score at week 3, 6, and 8 compared with placebo-treated patients (N = 75). A statistically significant effect (p <.05) in favor of gepirone ER was observed in mean change from baseline in HAM-D-17 total scores and for HAM-D factor I (anxiety/somatization) scores from week 2 onward. A statistically significant (p < or =.01) effect in favor of gepirone ER was observed in HAM-D-17 item 12 (anxiety, psychic) scores throughout the 8-week trial. There were significantly more patients in the gepirone ER group compared with the placebo group who were HAM-D-17 responders (p <.05) at endpoint and who met the criteria for HAM-D-17 remission at week 3 (p <.05) and weeks 6 and 8 (p <.01). Overall, gepirone ER was well tolerated, with rates of weight gain and sexual dysfunction comparable to placebo. Adverse events were generally mild to moderate. The most commonly reported adverse events were dizziness and nausea. CONCLUSIONS: Gepirone ER is an effective and well-tolerated treatment for patients with anxious depression.     

血清维生素B12水平对氟西汀抗抑郁症疗效的影响

目的探讨血清维生素B12水平对氟西汀治疗抑郁症疗效影响。方法测定30例抑郁症患者血清维生素B12水平,然后给予百忧解20mg/d,共治疗8周,治疗前及治疗结束时分别给予17项汉密尔顿抑郁量表(HAMD)评定。结果入组时抑郁症严重程度与血清维生素B12水平无相关性(r=-0.11,P>0.05);治疗结束时显著疗效组有效组和无效组比较血清维生素B12水平差异有统计学意义(F=10.34,P<0.01)。结论抑郁症患者血清维生素B12水平升高可能有助于提高抗抑郁剂疗效。     

Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression

BACKGROUND: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) are effective when used alone in the treatment of unipolar depression with psychotic features. The purpose of the present study was to examine the response to sertraline for patients with and without psychotic features using standard criteria such as recovery and remission. METHOD: An 8-week open-label trial of sertraline in depressed inpatients was conducted. Twenty-five subjects had DSM-IV major depressive disorder with psychotic features, and 25 had DSM-IV major depressive disorder without psychotic features. After a 1-week open washout, all subjects were rated using the Hamilton Rating Scale for Depression (HAM-D) and Brief Psychiatric Rating Scale (BPRS) at baseline. The HAM-D was administered weekly, and the BPRS was administered again only at the end of the 8-week trial. Medication dosage was started at 50 mg/day, increased to 100 mg/day after 1 week, and then increased up to 200 mg/day if subjects had not remitted. RESULTS: Depressed patients without psychosis responded significantly better than did depressed patients with psychosis using the criteria of remission (HAM-D score - 7; p =.001), response (HAM-D score - 50% of baseline score; p =.011), referral for electroconvulsive therapy (HAM-D score >/= 15; p =.011), or change in HAM-D scores (p =.016). Baseline HAM-D score and psychosis independently predicted response, whereas baseline BPRS scores did not, regardless of whether psychotic status was entered into the analyses. CONCLUSION: Psychotic depression responds more poorly than depression without psychosis to sertraline alone. Psychosis was a predictor of response independent of degree of depression and general psychopathology. Limitations due to an open-label design are discussed, as are differences between this study and others using SSRIs for psychotic depression.     

Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data

OBJECTIVES: Agomelatine has been shown to be safe and efficient in the treatment of major depressive disorder at 25 mg daily. The aim of this study was to gather preliminary data regarding the antidepressant efficacy of agomelatine in patients with bipolar I disorder experiencing a major depressive episode. METHODS: Bipolar I patients on lithium (n = 14) or valpromide (n = 7), with a Hamilton Rating Scale for Depression (HAM-D-17) total score > or = 18, were given adjunctive open-label agomelatine at 25 mg/day for a minimum of 6 weeks followed by an optional extension of up to an additional 46 weeks. RESULTS: Using intent-to-treat data, 81% of patients met criteria for marked improvement (>50% improvement from baseline in HAM-D score) at study endpoint. Patients were severely depressed at study entry (HAM-D of 25.2) and 47.6% responded as early as at one week of treatment. Nineteen patients entered the optional extension period for a mean of 211 days (range 6-325 days). Eleven patients completed the one-year extension on agomelatine. There were no dropouts due to adverse events during the acute phase of treatment (6 weeks). Six patients experienced serious adverse events during the one-year period. Three lithium-treated patients experienced manic or hypomanic episodes during the optional extension period, one of which was treatment-related. CONCLUSIONS: These results indicate the effectiveness of agomelatine 25 mg in the treatment of depressed bipolar I patients co-medicated with lithium or valpromide. A randomized controlled trial is planned to confirm these results.     

Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance

BACKGROUND: This 8-week, double-blind, multicenter study was undertaken to replicate, in a larger sample of patients with treatment-resistant major depressive disorder (MDD; DSM-IV criteria), the results of a pilot study of the olanzapine/fluoxetine combination. METHOD: The study was begun in August 1999. The primary entry criterion was a history of failure to respond to a selective serotonin reuptake inhibitor (SSRI). Patients (N = 500) who subsequently failed to respond to nortriptyline during an open-label lead-in phase were randomly assigned to 1 of 4 treatment groups: olanzapine (6-12 mg/day) plus fluoxetine (25-50 mg/day) combination, olanzapine (6-12 mg/day), fluoxetine (25-50 mg/day), or nortriptyline (25-175 mg/day). The primary outcome measure was baseline-to-endpoint mean change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: At the 8-week study endpoint, MADRS total scores decreased by a mean 8.7 points from baseline (28.5) with the olanzapine/fluoxetine combination, 7.0 points from baseline (28.4) with olanzapine (p = .08), 8.5 points from baseline (28.4) with fluoxetine (p = .84), and 7.5 points from baseline (28.8) with nortriptyline (p = .30), with no significant differences among the therapies. The olanzapine/fluoxetine combination was associated with significantly (p < or = .05) greater improvement (decrease) in MADRS scores than olanzapine at weeks 2, 4, 6, and 7; than fluoxetine at weeks 2 through 5; and than nortriptyline at weeks 1 through 4. A post hoc analysis of a subgroup of patients who had an SSRI treatment failure during their current MDD episode (N = 314) revealed that the olanzapine/fluoxetine combination group had a significantly (p = .005) greater decrease in MADRS scores than the olanzapine group at endpoint. Safety data for the olanzapine/fluoxetine combination were similar to those for its component monotherapies. CONCLUSIONS: The olanzapine/fluoxetine combination did not differ significantly from the other therapies at endpoint, although it demonstrated a more rapid response that was sustained until the end of treatment. The results raised several methodological questions, and recommendations are made regarding the criteria for study entry and randomization.     

Long-term weight gain in patients treated with open-label olanzapine in combination with fluoxetine for major depressive disorder

OBJECTIVE: Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g., age and gender) and correlates (e.g., cholesterol and glucose levels) of weight gain were investigated in OFC-treated patients with MDD. METHOD: Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for MDD were included (N = 549) in the current analyses of this 76-week, open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially clinically significant (PCS; > or = 7% increase from baseline) weight gain; time to PCS weight gain; and predictors and correlates of weight change were assessed. Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests was based upon p < or = .05. RESULTS: Mean baseline-to-endpoint weight change was 5.6 +/- 6.6 kg (12.3 +/- 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six percent of patients met criteria for PCS weight gain by 76 weeks, and the median time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female gender, younger age, and increased fluoxetine dose were predictors of weight gain; olanzapine dose was not. Patients with early (< or = 6 weeks) rapid PCS weight gain were 4.6 times more likely to gain substantial (> or = 15%) weight long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic blood pressure values were positively correlated with weight change. CONCLUSION: Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of patients meeting criteria for PCS weight gain (> or = 7%). The risk of weight gain may be significantly increased for OFC-treated patients who have a low BMI or who are female, younger, or taking high-dose fluoxetine. It is important that prescribers balance the risk of weight gain with the benefit of treatment for individual patients with depression.     

抗抑郁剂疗效的预测因素分析

目的:探索影响抑郁症患者抗抑郁剂疗效的预测因素。方法:241例抑郁症患者给予抗抑郁药治疗6周,治疗前后进行汉密顿抑郁量表17项(HAMD)评分,采用减分率评定疗效。分析人口学因素、基线HAMD、明尼苏达多项人格测定(MMPI-2)、认知功能评分及脑源性神经营养因子(BDNF)、5-羟色胺转运体(5-HTTLPR)和糖皮质激素受体(GR)3种基因多态对疗效的预测。结果:基线HAMD评分(β=0.771,P0.001)、MMPI-2中偏执(Pa)分(β=-0.322,P=0.032,R2=0.451)、连线测验B评分(TMT-B)(β=-0.045,P=0.013)、汉诺塔总分(β=-0.067,P=0.026)、数字广度(倒序)分(β=-0.974,P=0.025)及GR BclI基因G-等位基因携带者(P=0.05)与抗抑郁剂HAMD减分率有关。整合模型回归分析显示,结合基线HAMD评分(β=0.894,P0.001)、MMPI-2-Pa分(β=-0.155,P=0.036)和TMT-B分(β=-0.038,P=0.034)3个预测因子可解释57.1%的变异。结论:基线HAMD评分、MMPI-2-Pa分和TMT-B分可预测抗抑郁剂的疗效。     

氟伏沙明合并逍遥丸治疗抑郁症的临床观察

目的探讨氟伏沙明合并逍遥丸治疗抑郁症的疗效及安全性。方法将126例抑郁症患者随机分为研究组63例,对照组63例,分别给予氟伏沙明合并逍遥丸与单用氟伏沙明治疗,疗程8周。在治疗前及治疗后的第2、4、8周分别采用汉密尔顿抑郁量表(HAMD17)、汉密尔顿焦虑量表(HAMA)、临床疗效总评量表(CGI)进行疗效评定;用不良反应量表(TESS)评定不良反应。结果研究组痊愈41例,有效13例,有效率85.7%;对照组痊愈37例,有效7例,有效率71.0%,两组间有效率差异有统计学意义(χ2=4.013,P<0.05);与治疗前比较,两组治疗后的第2、4、8周HAMD17、HAMA及CGI评分比较,差异均具有统计学意义(P<0.01),研究组在治疗后4、8周末HAMD17和HAMA评分下降较对照组显著,两组间比较,差异具有统计学意义(P<0.05和P<0.01)。两组不良反应比较,研究组发生厌食和失眠的不良反应明显少于对照组,两组间比较差异均有统计学意义(P<0.05);结论氟伏沙明合并逍遥丸治疗抑郁症的疗效优于单用氟伏沙明,能提高临床有效率,且不良反应少,安全性高。     

瑞波西汀与西酞普兰治疗老年抑郁症的对照研究

目的评价瑞波西汀治疗首发老年抑郁症的疗效和安全性。方法采用随机、单盲、平行对照方法。受试者分别口服瑞波西汀胶囊8mg/d（4mg/d起,周增至治疗量）或西酞普兰40mg/d（20mg/d起,周增11至治疗量）。采用HAMD、HAMA、CGI及TESS评定疗效及不良反应。结果共搜集符合入组标准的老年抑郁症80例,其中瑞波西汀组40例（试验组）,因药物不良反应脱落1例,因其他原因中途退出1例,实际完成38例。西酞普兰组40例（对照组）。经治疗6周后,瑞波西汀组HAMD、HAMA总分明显下降,与治疗基线相比差异有统计学意义（P〈0.01）,但两组间相比差异则无统计学意义（P〉0.05）;瑞波西汀组有效率（HAMD减分率≥50%）为76.3%,西酞普兰组为77.5%,两组间相比差异无统计学意义（P〉0.05）;临床治愈率（HAMD、HAMA总分≤8）瑞波西汀组为57.9%,西酞普兰组为57.5%,两组间差异无统计学意义（P〉0.05）;两组间CGI评分差异亦无统计学意义。安全性分析显示,两组不良反应的症状和发生率相比差异均无统计学意义。结论瑞波西汀治疗首发老年期抑郁症的疗效与西酞普兰相当,安全性高,不良反应较少,是药物治疗老年抑郁症的新选择。     

Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors: an open-label,flexible-dose study

BACKGROUND: We report a clinical trial of olanzapine in the treatment of prominent apathy in the absence of depression in patients on long-term treatment with selective serotonin reuptake inhibitors (SSRIs) for nonpsychotic major depression. METHOD: Participants were 21 men and women who met DSM-IV criteria for major depressive disorder in full remission (Montgomery-Asberg Depression Rating Scale [MADRS] score < or = 12) who had been taking an SSRI for at least 3 months. Data are presented (last observation carried forward) based on 20 enrolled participants who completed at least 1 follow-up visit. Participants had significant symptoms of apathy, defined as a Clinical Global Impressions-Severity of Illness scale (CGI-S) score > or = 3, an Apathy Evaluation Scale (AES) score > 30, and a MADRS item 8 (inability to feel) score > or = 2. Participants with a personal or family history of psychosis were excluded. Olanzapine was titrated in 2.5-mg increments at weekly intervals, until CGI-S score improved > or = 2 points from baseline or > or = 1 point with dose-limiting side effects, and participants continued in the protocol for 8 weeks at a stable dose following this improvement. RESULTS: Improvement was clinically evident and demonstrable on all symptom assessments: AES (mean +/- SD change in score = -21.3 +/- 8.7; p < .0001), CGI-S (-2.7 +/- 0.9; p < .0001), MADRS (-5.6 +/- 5.9; p = .001), and MADRS item 8 (-2.2 +/- 1.4; p < .0001). The mean dose of olanzapine was 5.4 +/- 2.8 mg/day. CONCLUSION: These preliminary data suggest that olanzapine may be effective in treating apathy syndrome in nonpsychotic patients taking SSRIs.     

Antidepressant effects of magnetic resonance imaging—based stimulation on major depressive disorder: a double-blind randomized clinical trial

Antidepressant effects of magnetic resonance imaging (MRI) based stimulation have been reported in animal studies, but no human studies are available on subjects with major depressive disorder. Here, the efficacy of two diagnostic MRI protocols (echo-planar diffusion-weighted imaging (DWI) and T1-weighted imaging) was assessed in patients with major depressive disorder. In this double-blind randomized clinical trial, 51 patients with clinically proven major depressive disorder were randomly enrolled into three equal groups. All patients were receiving a selective serotonin reuptake inhibitor as the only antidepressant treatment. The first group received echo-planar DW stimulation (DWI group), the second group received T1-weighted stimulation (T1 group), and the third group experienced a similar condition without receiving any magnetic stimulation (sham group). The Hamilton rating scale for depression (HAMD24) and Beck depression inventory (BDI) were used to assess the effect of MR stimulation on depressive symptoms. In comparison to baseline, mean HAMD24 and BDI scores significantly (p?相似文献   

A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression

OBJECTIVE: Olanzapine-fluoxetine combination has shown efficacy in the acute treatment of depressive episodes in patients with bipolar I disorder. The present analyses examined the efficacy and safety of longer term treatment with olanzapine-fluoxetine combination or olanzapine monotherapy in a 6-month open-label extension study. METHOD: 376 patients with DSM-IV bipolar I disorder, depressed, who completed an acute trial entered the open-label study and received 1 week of olanzapine monotherapy (5-20 mg/day). At all subsequent visits, patients could choose between olanzapine monotherapy or olanzapine-fluoxetine combination (6/25, 6/50, or 12/50 mg/day). Three treatment groups were defined retrospectively according to the medication course taken from week 1: olanzapine, olanzapine-fluoxetine combination, or switched. The efficacy measures were the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions-Bipolar Version, and Young Mania Rating Scale. The study was conducted from July 2000 to May 2002. RESULTS: Among patients who started in remission, MADRS total scores did not change significantly from baseline to endpoint in the olanzapine-fluoxetine combination (0.8) or olanzapine (0.3) groups, but increased slightly in the switched (2.3, p = .02) group. For patients who started in nonremission, MADRS total scores decreased significantly in all groups (olanzapine-fluoxetine combination: -5.7, p = .001; olanzapine: -11.6, p = .004; switched: -6.4, p = .015). The majority of patients who entered the study in nonremission achieved remission (MADRS total score < or = 12) during the trial (olanzapine-fluoxetine combination: 66.7%, olanzapine: 64.7%, switched: 62.5%). The overall rate of depressive relapse was 27.4%, and the overall incidence of mania emergence was 5.9%. CONCLUSIONS: The present findings suggest that long-term treatment with olanzapine-fluoxetine combination may be a useful option for the management of depressive symptoms and carries a low risk of mania emergence.     

Efficacy of controlled-release paroxetine in the treatment of late-life depression

BACKGROUND: Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition. METHOD: In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score. RESULTS: The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo. CONCLUSION: Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.     

Ropinirole in treatment-resistant depression: a 16-week pilot study.

OBJECTIVE: The study aimed to assess the antidepressant efficacy and tolerability of adjunctive ropinirole in outpatients with treatment-resistant depression (TRD). METHOD: The study sample consisted of patients with a major depressive episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5 mg daily was added to tricyclic antidepressants or selective serotonin reuptake inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and 16. We defined response as a 50% or greater reduction of the Montgomery-Asberg Depression Rating Scale (MADRS) total score plus a score of 1 ("very much improved") or 2 ("much improved") on the Clinical Global Impression of Improvement scale at endpoint. Tolerability was monitored with the Dosage Record Treatment Emergent Symptom Scale. RESULTS: Seven patients had major depressive disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was 1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%) patients were responders. Two patients discontinued ropinirole because of dizziness. CONCLUSIONS: These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated.     

Use of effect size to determine optimal dose of duloxetine in major depressive disorder

OBJECTIVE: At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD(17) total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD. MATERIALS AND METHODS: Effect size for duloxetine 40mg, 60mg, 80mg, and 120mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40mg, 60mg, 80mg, and 120mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD(17) total score, from which were determined the effect size for HAMD(17) change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD(17) total score < or =7). RESULTS: A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40mg/day; 251 with 60mg/day; 363 with 80mg/day; and 196 with 120mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40-60mg/day dosage range. All dosages from 60 to 120mg were effective. The tolerability assessment indicated duloxetine at 40-120mg/day is well tolerated. Furthermore, the initial doses of 40-80mg/day were found to have comparable tolerability. CONCLUSIONS: The effect size analyses demonstrate that duloxetine 40mg has minimum efficacy, and that duloxetine 60-120mg/day is effective in the treatment of patients with MDD. An initial dose less than 60mg/day might provide better tolerability for some patients diagnosed with MDD.     

Switching patients from daily citalopram, paroxetine, or sertraline to once-weekly fluoxetine in the maintenance of response for depression

BACKGROUND: Major depressive disorder is frequently a chronic, recurrent condition necessitating maintenance treatment. For some patients, compliance with daily pharmacotherapy is difficult over time. As an alternative approach, a once-weekly administered formulation of fluoxetine has recently been made available. This raises the important question of whether once-weekly enteric-coated fluoxetine, 90 mg, is effective for maintenance of response in patients whose depressive symptoms have responded to daily dosing with selective serotonin reuptake inhibitors (SSRIs) such as citalopram, paroxetine, or sertraline. METHOD: Patients had met DSM-IV criteria for major depressive disorder prior to beginning treatment for their current episode, had received 6 to 52 weeks of treatment with citalopram (20-40 mg/day [N = 83]), paroxetine (20 mg/day [N = 77]), or sertraline (50-100 mg/day [N = 86]), and had responded to that treatment (Clinical Global Impressions-Severity of Illness [CGI-S] score < or = 2, modified 17-item Hamilton Rating Scale for Depression [HAM-D-17] score < or = 10). Patients meeting these criteria (N = 246) continued treatment with their current SSRI for 1 week, then were switched to open-label enteric-coated fluoxetine, 90 mg, taken once weekly for 12 weeks. Safety measures were comparisons of spontaneously reported and solicited treatment-emergent adverse events. Efficacy measures were percentages of patients who discontinued the study for relapse and lack of efficacy and comparison of change from baseline to endpoint in scores on the modified HAM-D-17, subscales of the HAM-D-28, and the CGI-S. Quality of life measures were assessed with the MOS 36-Item Short-Form Health Survey (SF-36). We hypothesized that the once-weekly administration of fluoxetine could be safely and effectively initiated among subjects who had been stabilized on daily SSRI treatment. RESULTS: Seventy-nine percent of patients successfully completed a switch to enteric-coated fluoxetine, 90 mg, with 9.3% discontinuing due to relapse or lack of efficacy. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated in all groups. No significant increases were found in the HAM-D-17 total, HAM-D-28 subscores, or CGI-S score. Patients showed improvement from baseline to endpoint in most of the SF-36 health concepts. CONCLUSION: Enteric-coated fluoxetine taken once weekly appears to be well tolerated and efficacious in patients who responded to acute therapy with other SSRIs and were subsequently switched to fluoxetine once weekly for continuation/maintenance therapy.     

Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study

This double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with selective serotonin reuptake inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder, comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall, 62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed the study. The mean change in HAM-D and HAM-A total scores from baseline to Week 8 (primary endpoint) was significantly greater with quetiapine (mean dose 182 mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002), respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by Week 1) and continued through to Week 8. Significant differences (P<.05) from baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular symptoms). Response (> or =50% decrease in total score) was higher for quetiapine than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28% (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo: HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global Assessment Scale showed that quetiapine was significantly more effective than placebo. For quetiapine, adverse events (AEs) were similar to those previously observed; sedation/somnolence/lethargy was the most commonly reported. Here quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy in patients with major depression, comorbid anxiety, and residual depressive symptoms, with no unexpected tolerability issues. Further studies are warranted.