氟伏沙明合并利培酮治疗抑郁症的对照研究

目的比较氟伏沙明合并利培酮及单用氟伏沙明两者在治疗抑郁症方面的疗效及安全性。方法将门诊66例抑郁症患者随机分为研究组（氟伏沙明合并利培酮治疗）和对照组（单用氟伏沙明治疗）。疗程6周。在治疗前及治疗第1、2、4、6周末用HAMD量表评定临床疗效，用TESS量表评定药物不良反应，并进行比较分析。结果在治疗第6周末研究组显效率为66.7%，总有效率为87.9%；对照组分别为63.6%和84.8%。两组显效率和总有效率相近。差异均无显著性（P〉0.05）。但研究组较对照组起效快，在对焦虑、躯体化、认知障碍和睡眠障碍的改善上研究组优于对照组。两组不良反应接近。结论氟伏沙明合并利培酮治疗抑郁症疗效肯定，不良反应少。     

A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression

Deborah Roth, Jeffrey Mattes, K. Harnett Sheehan and David V. Sheehan: A Double-Blind Comparison of Fluvoxamine, Desipramine and Placebo in Outpatients with Depression. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 929–939.

1. 1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder.

2. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated.

3. 3. Studies of major depression ought to be designed to last 8–10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.

CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine

Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n=52) in comparison to healthy control subjects (n=73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.     

Escitalopram in the treatment of anxiety symptoms associated with depression

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.     

Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P = 0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P = 0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.     

氟伏沙明合并氯氮平治疗强迫症的疗效比较

目的探讨氟伏沙明合并氯氮平治疗强迫症的疗效。方法45例强迫症患者随机分为氟伏沙明合并氯氮平治疗组和单独氟伏沙明治疗组。疗程8周。采用强迫症量表（Y—BOCS）、汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）评定疗效。结果治疗结束时两组Y—BOCS、HAMA、HAMD的评分均显著降低,更以合并氯氮平组明显。结论氟伏沙明合并氯氮平治疗强迫症可以增加疗效。     

Duloxetine in treatment of anxiety symptoms associated with depression

Most patients with major depressive disorder (MDD) have symptoms of anxiety associated with their depression. Duloxetine, a potent and balanced dual serotonin and norepinephrine reuptake inhibitor, is effective in the treatmentof depression. We investigated its effects in treating the symptoms of anxiety in depressed patients. This investigation includes all the placebo-controlled studies of duloxetine in MDD but focuses on four trials in which duloxetine was superior to placebo on the primary outcome measure of the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score. Studies 1 and 2 included duloxetine at 60 mg/d (the recommended starting and therapeutic dose) and placebo. Study 3 included duloxetine 120 mg/d (administered as 60 mg b.i.d.), fluoxetine 20 mg/d, and placebo. Study 4 included duloxetine 40 mg/d (administered as 20 mg b.i.d.), duloxetine 80 mg/d (administered as 40 mg b.i.d.), paroxetine 20 mg/d, and placebo. Anxiety was assessed in all studies using the HAMD anxiety/somatization subfactor and the anxiety-psychic item (HAMD Item 10). Studies 3 and 4 also included the Hamilton Anxiety Rating Scale (HAMA). Across the four studies, duloxetine at doses of >/=60 mg was compared with placebo on 10 outcomes and with either paroxetine or fluoxetine on 6 outcomes. In 8 comparisons, mean improvement for duloxetine was significantly greater than placebo at the last study visit and/or across all study visits. In 3 comparisons, the mean improvement for duloxetine was significantly greater than paroxetine or fluoxetine. In these studies, duloxetine provided rapid relief of anxiety symptoms associated with depression. Previous reports have summarized duloxetine's efficacy in treating the core emotional symptoms and painful physical symptoms associated with depression. Duloxetine's efficacy in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical symptoms, may be attributed to dual reuptake inhibition of both serotonin and norepinephrine. Efficacy in these three key symptom domains may in turn explain the high probabilities of remission (43-57%) observed in these studies.     

帕罗西汀合用奎硫平治疗抑郁症的随机对照研究

目的评估帕罗西汀合用奎硫平治疗无精神病性症状的抑郁症疗效和安全性。方法将符合入组标准和排除标准的无精神病性症状的抑郁症患者120例,随机分配到帕罗西汀合用奎硫平治疗组(研究组)和单用帕罗西汀治疗组(对照组),在入组时(第0天)和第7、14、21、28、42、56天分别评定HAMD和TESS,并测量生命体征;在治疗开始前、第4、8周末各进行一次血常规检查、尿常规检查、血生化、心电图检查。结果第1周末时,研究组的HAMD评分即下降了29.75%,显著高于对照组(12.05%),这种差异一直保持到研究结束,表明帕罗西汀合用奎硫平起效迅速;研究组的显效率(痊愈 显著进步)为85%,显著高于对照组(51.7%,)(χ2=15.93,P=0.001)。结论帕罗西汀合用奎硫平治疗无精神病性症状的抑郁症起效快,疗效优于单用帕罗西汀,不良反应无明显增多或加重。     

氟伏沙明与氯米帕明治疗青少年强迫症的对照研究

目的 比较氟伏沙明与氯米帕明治疗青少年期强迫症的疗效和不良反应.方法 共纳入强迫症患者42例,随机分为氟伏沙明组和氯米帕明组,疗程8周.应用耶鲁-布朗强迫症量表(Y-BOCS)、汉密尔顿焦虑量表(HAMA)评定疗效,治疗中需处理的不良反应症状量表(TESS)评价不良反应.结果 氟伏沙明组治疗总有效率86.4％,氯米帕明组治疗总有效率86.4％,两组比较差异无统计学意义(P＞0.05).两组治疗后第4、8周末Y-BOCS评分、HAMA评分与治疗前比较差异有显著统计学意义(P＜0.01).氟伏沙明组与氯米帕明组不良反应发生率差异有统计学意义(P＜0.05).结论 氟伏沙明对于青少年期强迫症状的治疗是安全有效的.     

Predictive value of amino acids in the treatment of major depression with fluvoxamine

Sixteen outpatients (mean age +/- SD 50.18 +/- 11.55 years; 11 females and 5 males) affected by major depression without melancholia (DSM-IV) were included in the study. The control group consisted of 11 healthy volunteers (mean age +/- SD 39.90 +/- 13.39 years; 2 females and 9 males). Patients were treated with fluvoxamine (FVX) 100-300 mg daily. Clinical assessment was performed using the Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical Global Impression Scale (CGI) at basal time (T(0)), after 4 weeks and after 8 weeks (T(8)). Plasma and platelet amino acid levels were determined at T(0) in all the subjects and also at T(8) in depressed patients. A significant clinical improvement was observed in depressed patients according to the HRS-A (p = 0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = -0.53, p = 0.049) was found between platelet levels of valine and HRS-D improvement rate. Patients showed significantly higher tyrosine/large neutral amino acids (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good response to a serotonergic drug like FVX.     

儿茶酚氧位甲基转移酶基因多态性与抑郁症认知功能的关联性研究

目的探讨儿茶酚氧位甲基转移酶（COMT）基因多态性与抑郁症认知功能及其严重程度的关系。方法采用病例一对照研究。应用聚合酶链反应（PCR）及聚丙烯酰胺凝胶电泳（PAGE）方法．检测抑郁症患者（患者组）和健康志愿者（对照组）COMT基因多态性分布。患者组评定24项汉密尔顿抑郁量表（HAMD-24）、威斯康星卡片分类测验（WCST）、中国韦氏成人记忆量表（WMS—RC）、连线A、B测验。结果COMT等位基因与基因型频率在患者组和对照组内均有显著性差异（Χ^2检验,P均〈0．01）,在两组间无显著性差异（Χ^2检验,P均〉0．05）;患者组COMT等位基因、基因型之间在WCST、WMS—RC和连线A、B测验无显著性差异（F检验,P均〉0．05）,但在HAMD-24认识障碍因子分上均有显著性差异（F检验,P均〈0．05）;患者组基因型A／A与认识障碍（r=-0．210,P=0．036）、绝望感（r=-0．331,P=0．001）均呈负相关;等位基因A与绝望感呈负相关（r=-0．220,P=0．028）;等位基因G与认识障碍（r=0．210,P=0．036）、绝望感（r=0．331,P=0．001）均呈正相关。在WCST测验中,等位基因G与持续错误数呈正相关（r=0．341,P=0．000）;在WMS—RC测验中,等住基因G与数字广度（倒背）呈负相关（r=-0．327,P=0．001）。结论提示COMT基因多态性与抑郁症患者的疾病严重程度及认知功能的改变存在相关性。     

The norepinephrine transporter gene is associated with the retardation symptoms of major depressive disorder in the Han Chinese population

The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder.Consequently,the norepinephrine transporter gene is an attractive candidate in major depressive disorder research.In the present study,we evaluated the depression symptoms of subjects with major depressive disorder,who were all from the North of China and of Han Chinese origin,using the Hamilton Depression Scale.We examined the rela-tionship between two single nucleotide polymorphisms in the norepinephrine transporter,rs2242446 and rs5569,and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program.rs5569 was associated with depressed mood,and the GG genotype may be a risk factor for this;rs2242446 was associated with work and interest,and the TT genotype may be a risk factor for loss of interest.Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Han Chinese population.     

帕罗西汀合并奥氮平治疗伴躯体症状抑郁症的对照研究

目的探讨帕罗西汀合并奥氮平治疗伴躯体症状抑郁症的疗效及安全性。方法66例伴躯体症状的抑郁症患者随机分为帕罗西汀组33例,帕罗西汀合用奥氮平组33例,共治疗8周。于治疗前,治疗后1、2、4、8周末采用汉密尔顿抑郁量表（HAMD）,副反应量表（TESS）评定疗效和副反应。结果帕罗西汀合用小剂量奥氮平组疗效显著,合用药组与单用药组的显效率分别是84.85%和60.61%,差异有显著性（χ^2=4.89,P〈0.05）。两组的HAMD因子分在焦虑/躯体化和睡眠障碍方面差异有显著性;两组副作用均较小。结论帕罗西汀合用小剂量奥氮平治疗抑郁症起效快,可提高疗效,能迅速改善睡眠障碍和躯体症状。     

舍曲林合并氟伏沙明治疗强迫症的对照研究

目的 探讨舍曲林合并氟伏沙明治疗强迫症的疗效及安全性.方法 91例强迫症患者随机分为三组:舍曲林组、氟伏沙明组各30例,两药合用组31例,疗程为8周.采用Yale- Brown强迫症状量表( Y- BOCS)、个人和社会功能评定量表(PSP)评定疗效和社会功能,采用症状量表(TESS)评定安全性.结果 治疗8周末,三组治疗的显效率分别为:舍曲林组43.3％、氟伏沙明组40.0％,两药合用组71.0％,三组间比较差异有统计学意义(P＜0.05).三组Y- BOCS评分均显著下降,PSP评分均显著提高,方差分析显示三组间差异有统计学意义(P＜0.05),进一步两两比较,两药合并组与单药治疗组之间差异有统计学意义(P＜0.01).三组患者在口干、便秘、头晕、乏力、恶心、焦虑、失眠的不良反应方面差异无统计学意义(P＞0.05).TESS评分在治疗后第2、4、6及8周末差异均无统计学意义(P＞0.05).结论 舍曲林合并氟伏沙明治疗强迫症可以增强疗效,安全性较好.     

Visuo-motor coordination is normal in patients with major depression

Depression and Parkinson's disease (PD) are strongly associated with each other. Similarly, deficient visuo-motor coordination (VMC) accompanies PD from its earliest clinical stages. This double association suggests that a VMC dysfunction would be found in patients with major depression. Previous reports are ambiguous on this matter. Therefore, the present study was undertaken in order to determine whether MD patients pass or fail a VMC test on which PD patients are known to be deficient.

Sixty-five MD patients were tested. Fifty-four (83%) had normal VMC. VMC was found to be independent of age, disease duration, severity of depression, or treatment. A deficit was found in 12 patients (17%). In this group too, VMC capabilities did not correlate with depression, or its treatment.

These results negate an effect of depression, its accompanying frontal cortical changes, or its treatment on VMC. We propose that abnormal VMC in depression indicates coexisting illness, including possible preclinical PD.     

Changes in brain metabolism associated with remission in unipolar major depression

OBJECTIVE: Functional brain correlates of remission in patients with major depressive disorder (MDD) are measured with positron emission tomography (PET) and 18F-fluorodeoxyglucose. METHOD: Glucose metabolism was measured in patients (n = 41) with moderate to severe MDD during acute depression and in the remitted state defined as a period of asymptomatic condition over 12 weeks. Data analyses used a region-of-interest (ROI) approach and statistical parametric mapping (SPM). RESULTS: There were significant decreases in metabolism upon remission with respect to the baseline scan in left prefrontal, anterior temporal and anterior cingulate cortex and bilateral thalamus (SPM analysis) and bilateral putamen and cerebellum (SPM and ROI analyses). There was a significant asymmetry in prefrontal and anterior cingulate cortex metabolism with lower metabolism in the left hemisphere that persisted despite clinical remission. CONCLUSION: These findings support the hypothesis that selective monoamine reuptake inhibition leads to an attenuation of a brain circuit that mediates depressive symptomatology.     

Efficacy of fluvoxamine in the treatment of major depression with comorbid anxiety disorders.

BACKGROUND: Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared with major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in depressive symptoms and anxiety levels in outpatients with major depression with comorbid anxiety disorder following 12 weeks of open treatment with fluvoxamine. METHOD: We enrolled 30 outpatients (mean +/- SD age = 39.4 +/- 11.3 years; 16 women and 14 men) with DSM-IV major depressive disorder accompanied by one or more current comorbid DSM-IV anxiety disorders in our study. Patients were treated openly with fluvoxamine initiated at 50 mg/day, with an upward titration to a maximum of 200 mg/day (mean +/- SD dose = 143 +/- 45 mg/day). Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales for both depression and anxiety. Intent-to-treat analysis was used to assess outcome. RESULTS: The mean +/- SD number of comorbid anxiety disorders per patient was 2.1 +/- 1.1. Following fluvoxamine treatment, the mean +/- SD HAM-D-17 score dropped from 20.2 +/- 3.3 to 1 1.0 +/- 7.0 (p < .0001). The mean +/- SD depression CGI-S score dropped from 4.0 +/- 0.6 to 2.4 +/- 1.1 (p < .0001), and the mean +/- SD anxiety CGI-S score decreased from 4.1 +/- 0.8 to 2.5 +/- 1.2 (p < .0001). Eighteen (60%) of the 30 patients had CGI-I scores < or = 2 for both anxiety and depression at endpoint, with 53% showing a > or = 50% reduction in HAM-D-17 scores at endpoint. CONCLUSION: Although preliminary, our findings suggest that fluvoxamine is effective in treating outpatients with major depression with comorbid anxiety disorder, having a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are needed, in a larger sample, to confirm our findings.     

帕罗西汀治疗伴躯体症状抑郁对照研究

目的探讨帕罗西汀治疗伴躯体症状抑郁症的疗效及安全性。方法将80例伴躯体症状的抑郁症患者随机分为阿米替林组40例,帕罗西汀组40例,共治疗6周,采用汉米尔顿抑郁量表(HAMD)和临床总体评定量表(CGI)评定临床疗效,采用副反应量表(TESS)评定副反应。结果帕罗西汀组与阿米替林组治疗前后HAMD和CGI-SI分值比较均有显著性差异,而两组减分相比治疗前后无显著性差异,帕罗西汀组副作用明显比阿米替林组小,服用方便,依从性好。结论帕罗西汀是治疗伴躯体症状抑郁症的理想药物。     

氟伏沙明联合奥氮平治疗伴精神病性症状抑郁症对照研究

目的：探讨氟伏沙明合并奥氮平对有精神病性症状抑郁症的临床疗效及安全性。方法：将115例患者随机分为氟伏沙明联合奥氮平组、氟伏沙明联合舒必利组,疗程8周。采用汉密尔顿抑郁量表（HAMD）、简明精神病评定量表（BPRS）观察疗效,用治疗中出现的症状量表（TESS）评定不良反应。结果：治疗8周两组BPRS、HAMD总分及各因子分均较治疗前显著降低（P均〈0.01）;氟伏沙明联合奥氮平组起效较快,疗效亦较好。两组不良反应接近。结论：氟伏沙明联合奥氮平治疗有精神病性症状的抑郁症疗效肯定,安全性高。