Efficacy and safety of add on low-dose mirtazapine in depression

Objectives:

Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population.

Materials and Methods:

In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks.

Results:

There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups.

Conclusion:

Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients.KEY WORDS: Add-on, depression, mirtazapine, selective serotonin reuptake inhibitor     

舍曲林与西酞普兰治疗帕金森病合并抑郁的差别的临床研究

目的：研究舍曲林、西酞普兰治疗帕金森病合并抑郁的疗效及安全性。方法帕金森病合并抑郁患者随机分为舍曲林治疗组及西酞普兰治疗组,采用抑郁自评量表（SDS）在治疗前、治疗6周及治疗12周评价疗效。结果西酞普兰组早期起效快于舍曲林组,但12周后有效率无明显差别,两组均未见严重不良反应。结论常规剂量的舍曲林和西酞普兰治疗帕金森病伴发抑郁均安全有效。     

A placebo-controlled, randomized withdrawal study of sertraline for major depressive disorder in Japan

The objective of this double-blind, placebo-controlled, multicentre randomized withdrawal study was to evaluate the efficacy and tolerability of sertraline for 16 weeks in treating Japanese patients with major depressive disorder (MDD) who had achieved a response to 8 weeks of sertraline treatment. Patients (n=361) were initially treated with 8 weeks of open-label sertraline treatment followed by 16 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. A total of 235 patients (65.1%) were entered to the double-blind phase and randomly assigned to receive sertraline (n=117) or placebo (n=118). A significantly (P=0.016) lower relapse rate was found for sertraline (8.5%) compared to placebo (19.5%) during the double-blind phase. Examination of time-to-relapse showed that the relapse free rate curve was significantly higher for sertraline (log-rank test, P=0.026) than placebo. Mean changes from beginning to end of the double-blind phase on measure of depressive symptoms, quality of life and global improvement also significantly favoured sertraline over placebo. Sertraline was well-tolerated, with similar adverse events as found in previous studies. These results confirm the efficacy of sertraline in preventing the relapse of MDD in Japanese patients.     

A Double-Blind Comparison of Sertraline and Imipramine in Outpatients with Major Depression: Acute (8 Weeks) and Continuation (16 Weeks) Treatment

In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared to those of imipramine, during an 8-week acute treatment phase followed by a 16-week continuation treatment phase in treatment responders. A total of 104 patients who met DSM-III-R criteria for major depression, HAM-D 17-item≥18 and Raskin Depression score>Covi Anxiety score, were randomized to receive either sertraline or imipramine. The initial daily dosage of 50 mg of sertraline or imipramine was rapidly titrated upwards in increments of 50 mg/day at weekly intervals, tolerability permitting, to a maximum of 200 mg/day by the fourth week. Eighty-eight patients completed at least 3 weeks of treatment and were included in the efficacy evaluable population. Both treatment groups demonstrated similar improvements on depression and anxiety rating scales during acute treatment, however, sertraline demonstrated significantly more improvement relative to imipramine on the HAM-D and Covi Anxiety scales after 1 week of treatment. Sertraline was more effective (HAM-D 17-item, CGI-S, SCL-56 Total score, SCL-56 Depression score, Covi Anxiety score) than imipramine in reducing depressive symptoms at the end of 24 weeks of treatment. There were significant improvements in all rating scales at week 24 relative to week 8 in the sertraline group but not in the imipramine group. The SCL-56 Total score, SCL-56 Depression score, Raskin Depression score and Covi Anxiety score at week 24 relative to week 8 showed significantly greater improvement in the sertraline group compared to the imipramine group. Imipramine was associated with a significantly higher incidence of dry mouth, sweating, constipation, palpitations, and a significantly higher heart rate and blood pressure. Sertraline was associated with a significantly higher incidence of diarrhoea/loose stools and insomnia. This study demonstrated a faster onset of therapeutic effect for sertraline relative to imipramine, reflecting the initiation of sertraline in a therapeutic dose of 50 mg/day and the need for gradual titration of imipramine to a therapeutic dose, at the beginning of treatment. Although efficacy was similar in both treatment groups at the end of the 8 weeks of acute therapy, sertraline-treated patients continued to manifest gradual improvements in depressive and anxiety symptoms during the 16 weeks of continuation therapy such that sertraline-treated patients were significantly more improved at the end of 24 weeks of therapy. © 1997 John Wiley & Sons, Ltd.     

A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients

OBJECTIVE: This randomised, double-blind, fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: Patients with a primary diagnosis of MDD and baseline Montgomery-Asberg Depression Rating Scale (MADRS) >or= 30 were randomised to 24 weeks of double-blind treatment with fixed doses of either escitalopram (20 mg) (n = 232) or paroxetine (40 mg) (n = 227). The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (Week 24) in MADRS total score (last observation carried forward, LOCF). MAIN OUTCOME MEASURES; RESULTS: At endpoint (24 weeks), the mean change from baseline in MADRS total score was -25.2 for patients treated with escitalopram (n = 228) and -23.1 for patients with paroxetine (n = 223), resulting in a difference of 2.1 points (p < 0.05). The difference in the change in the MADRS total score (LOCF) was significantly in favour of escitalopram from Week 8 onwards. The proportion of remitters (MADRS or= 35), there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram (p < 0.05). The overall withdrawal rate for patients treated with escitalopram (19%) was significantly lower than with paroxetine (32%) (p < 0.01). The withdrawal rate due to adverse events was significantly lower for escitalopram (8%) compared to paroxetine (16%) (p < 0.05). There were no significant differences in the incidence of individual adverse events during treatment. CONCLUSION: Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients.     

帕罗西汀和西酞普兰治疗抑郁症自杀未遂患者的疗效比较

目的:比较帕罗西汀(赛乐特)和西酞普兰(喜普妙)治疗抑郁症自杀未遂患者的疗效和安全性。方法:用随机对照方法对75例抑郁症自杀未遂患者进行帕罗西汀(试验组)和西酞普兰(对照组)治疗8周,采用汉密尔顿抑郁量表(HAMD)评定疗效,用副反应量表(TESS)评定不良反应。结果:试验组在治疗后4周的HAMD减分值及减分率低于对照组,差异均有统计学意义(P<0.05)。两组在治疗后4周的显效率差异有统计学意义(P<0.05)。两组副作用比较无统计学意义(P>0.05)。结论:在系统治疗抑郁症自杀未遂患者时,西酞普兰抗抑郁作用显效快于帕罗西汀,两药安全性相仿。     

Citalopram concentrations and response in obsessive-compulsive disorder. Preliminary results

OBJECTIVE: Citalopram, a highly potent SSRI, is effective in the treatment of depressive disorders and obsessive-compulsive disorder (OCD); however, very few studies have reported concentration-effect relationships for SSRIs. The aim of this study was to investigate the relationship between citalopram concentrations and clinical response in patients with OCD. METHODS AND STUDY DESIGN: Fifteen patients (aged 18-65 years) with a DSM-IV diagnosis of OCD were included in this open-label, single-blind study. Citalopram was started at a dosage of 20 mg/day; the dosage was increased to a maximum of 60 mg/day by the third week, on the basis of clinical need and tolerability. The dosage then remained unchanged until the end of the 10-week study. Clinical assessments were made at baseline, weekly for the first four weeks and then at weeks 6, 8 and 10. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression Scale (CGI) and the Hamilton Depression Rating Scale (HDRS). Plasma citalopram concentrations were determined using a high performance liquid chromatography method after solid phase extraction. RESULTS: One patient was withdrawn from the study because of poor compliance. Of the 14 patients who completed the study, nine did not meet the treatment response criterion of an improvement of >25% from the baseline total Y-BOCS score and a score of < or =3 for the global improvement item of the CGI (these patients were termed non-responders), while five did (responders). There were no differences in the main demographic and baseline clinical variables between responders and non-responders. Steady-state citalopram concentrations were similar in the two groups, suggesting that the anti-obsessional effects of citalopram were not related to pharmacokinetic differences between responders and non-responders. There was no linear relationship between steady-state citalopram concentrations and response. The citalopram concentrations and Y-BOCS scores of individual responders obtained at baseline and various study timepoints showed a sigmoid relationship when analysed using the E(max) (maximum change in Y-BOCS score) model, with a mean EC(50) value (drug concentration that elicits 50% of the E(max)) of 152 microg/L, whereas a similar analysis of the non-responders generated a flat line. CONCLUSION: The results of this preliminary study suggest that plasma citalopram concentrations may be related to the clinical response in responders, but do not seem to account for the lack of clinical effect in non-responders. These data, as well as the usefulness of the model in relating plasma concentrations to response, even after repeated administration, need to be validated by further investigations.     

The effect of escitalopram on sleep problems in depressed patients

The results from three 8-week escitalopram studies in major depressive disorder are presented with respect to efficacy and the effect on sleep quality, both in the full population and the subpopulation of patients with sleep problems at baseline.Analysis of pooled data from these randomized, double-blind, placebo-controlled, studies in which citalopram was the active reference, showed a significant improvement for escitalopram-treated patients (n = 52.0) in the Montgomery-Asberg depression rating scale (MADRS) item 4 ('reduced sleep') scores at weeks 6 and 8 compared with placebo (n=398; p < 0.01) and at weeks 4, 6 and 8 (n = 403; p < 0.05) compared with citalopram.Escitalopram-treated patients with sleep problems (MADRS item 4 score > or = 4; n = 254) at baseline showed a statistically significant improvement in mean MADRS item 4 scores at weeks 4, 6 and 8 compared with patients treated with placebo (n = 191; p < 0.05) or citalopram (n = 193; p < 0.01). These patients also showed a statistically significant (p < 0.05) and clinically relevant improvement in MADRS total score after escitalopram treatment compared with citalopram at weeks 1, 4, 6 and 8 (observed cases) and endpoint (-2.45; last observation carried forward [LOCF]). Statistical significance in favour of escitalopram versus placebo treatment was found at all visits, including endpoint (-4.2; LOCF).Thus, these post-hoc analyses suggest that escitalopram has a significant beneficial effect compared with placebo or citalopram in reducing sleep disturbance in patients suffering from major depressive disorder. The effect of escitalopram in improving 'reduced sleep' scores was clearly seen in patients with more severe sleep disturbance at baseline. A further prospective study is needed to establish this useful clinical effect in insomniac depressives.     

西酞普兰和阿米替林治疗老年抑郁症临床研究

目的 探讨西酞普兰与阿米替林治疗老年抑郁症的疗效及副反应。方法 将72例符合CCMD-3诊断标准的老年抑郁症患者采用随机分组的对照方法，分为西酞普兰组和阿米替林组治疗8周，采用四级临床疗效及HAMD(汉密尔顿抑郁量表)、HAMA(汉密尔顿焦虑量表)和TESS(副反应量表)评定疗效和不良反应。结果 西酞普兰与阿米替林对老年抑郁症的疗效相似，西酞普兰副反应较阿米替林少而轻。结论 西酞普兰是一个既有效又安全的新型抗抑郁药，适合对老年抑郁症的治疗，患者有较好的耐受性。     

西酞普兰与氟西汀治疗抑郁症的药物经济学分析

目的:比较西酞普兰与氟西汀治疗抑郁症的成本与效果。方法:40例抑郁症患者随机分为A、B组,分别给予西酞普兰、氟西汀治疗6wk,应用药物经济学最小成本分析方法进行评价。结果:A、B组总有效率均为80%,成本分别为736·16、743·09元,成本-效果比分别为920·20、928·86。结论:西酞普兰为较佳方案。     

Prediction of the response to citalopram and reboxetine in post-stroke depressed patients

Rationale and objective Depression is a significant complication of stroke. The effectiveness of antidepressant drugs in the management of post-stroke depression (PSD) has been widely investigated. However, the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies. Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by anxious depression or retarded depression.Methods This was a randomized double-blind study. Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table. Randomisation was planned so that 50% of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50% were assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score depressive symptoms.Results Both citalopram and reboxetine showed good safety and tolerability. Citalopram exhibited greater efficacy in anxious depressed patients, while reboxetine was more effective in retarded depressed patients.Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.     

氟西汀与西酞普兰治疗酒依赖戒断患者的对照研究

目的：比较氟西汀与西酞普兰对酒依赖戒断患者的疗效和不良反应。方法：将66例酒依赖戒断患者随机分为氟西汀组（31例）和西酞普兰组（35例），疗程6周；于治疗前及治疗后1、2、4、6周采用汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）、治疗时出现的症状量表（TESS）评定疗效与不良反应。结果：氟西汀与西酞普兰对酒依赖戒断患者的治疗均有明显疗效，氟西汀对抑郁症状的改善优于西酞普兰，统计学上存在显著性差异（P〈0.05），不良反应无显著性差异（P〉0．05）。结论：氟西汀与西酞普兰治疗酒依赖戒断患者安全有效。     

西酞普兰合并低剂量阿米替林与帕罗西汀治疗抑郁症的疗效观察

目的探讨西酞普兰合并低剂量阿米替林与帕罗西汀治疗抑郁症的疗效价值和安全性。方法对2009年1月-2009年10月我院门诊及住院抑郁症患者112例,随机分为西酞普兰合并低剂量阿米替林组和帕罗西汀组各56例,疗程6周,采用汉密顿抑郁量表（HAMD）和不良反应量表（TESS）在治疗前、后1、2、4、6周末评定药物疗效和不良反应。结果西酞普兰合并低剂量阿米替林和帕罗西汀两组治疗1～2周前后HAMD评分差异有显著性（P〈0．05）,治疗4—6周,两组差异无显著性（P〉0．05）,西酞普兰合并低剂量阿米替林组不良反应总发生率为26．79％,帕罗西汀则为46．43％,两组差异有显著性（P〈0．05）。结论西酞普兰合并低剂量阿米替林与帕罗西汀治疗抑郁症均有效,不良反应较轻,但西酞普兰合并低剂量阿米替林更安全,服用方便,不良反应更小,可作为治疗抑郁症的首选联合药物。     

A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression

One hundred and ninety-seven outpatients with atypical depression [Atypical Depression Diagnostic Scale (ADDS) score=4] were randomized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre, parallel-group clinical trial. Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide. If the therapeutic response was not satisfactory after 4 weeks, the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide. Primary efficacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impression of Improvement (CGI-I) response rate (much or very much improved) at study endpoint. Secondary efficacy evaluations included the ADDS, the Hamilton Anxiety Scale (HAMA), the Leeds Sleep Scale, and the Battelle Quality of Life Battery (BQOLB). In the analysis of the 172 patient efficacy-evaluable population, there was significant baseline to endpoint improvement in all primary and secondary efficacy assessments after treatment with either sertraline or moclobemide. At the endpoint, the proportion of responders on CGI-I, was 77.5% in the sertraline group and 67.5% in the moclobemide group (p=0.052). The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group. Sertraline also resulted in a significantly (p < 0.05) greater degree of improvement at the endpoint, compared with moclobemide, in the proportion of remitters on the HAMA (total score < or = 7), ADDS Category IID (Rejection Sensitivity), Leeds Sleep Factor 4 (Integrity of Behaviour Following Awakening), and on three dimensions of the BQOLB (Energy/Vitality, Social Interaction and Life Satisfaction). There were no other significant differences between treatment groups. Overall, both medications were well tolerated. In this study, both sertraline and moclobemide improved the symptoms of atypical depression.     

Psychosocial functioning during the treatment of major depressive disorder with fluoxetine

BACKGROUND: Major depressive disorder (MDD) is associated with significant disability, having a profound impact on psychosocial functioning. Therefore, studying the impact of treatment on psychosocial functioning in MDD could help further improve the standard of care. METHODS: Two hundred twenty-two MDD outpatients were treated openly with 20 mg fluoxetine for 8 weeks. The self-report version of the Social Adjustment Scale was administered at baseline and during the final visit. We then tested for the relationships between (1) self-report version of the Social Adjustment Scale scores at baseline and clinical response, (2) nonresponse, response and remission status and overall psychosocial adjustment at end point, (3) the number/severity of residual depressive symptoms and overall psychosocial adjustment at end point in responders, and (4) the time to onset of response and overall psychosocial adjustment at end point. RESULTS: An earlier onset of clinical response predicted better overall psychosocial functioning at end point (P = 0.0440). Responders (n = 128) demonstrated better overall psychosocial adjustment at end point than nonresponders (P = 0.0003), while remitters (n = 64) demonstrated better overall psychosocial adjustment at end point than nonremitted responders (P = 0.0031). In fact, a greater number/severity of residual symptoms predicted poorer overall psychosocial adjustment at end point in responders (P = 0.0011). Psychosocial functioning at baseline did not predict response. CONCLUSIONS: While MDD patients appear equally likely to respond to treatment with fluoxetine, regardless of their level of functioning immediately before treatment, the above results stress the importance of achieving early symptom improvement then followed by full remission of depressive symptoms with respect to restoring psychosocial functioning in MDD.     

Addition of risperidone to sertraline improves sertraline-resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline

In the present study, we examined the efficacy of risperidone addition on sertraline-resistant depressed patients and the effects of risperidone on the metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3 (4 weeks after risperidone addition). Plasma levels of sertraline and desmethylsertraline did not change after risperidone addition. Serum BDNF levels in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition); in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition). These results suggest that the addition of risperidone to sertraline is effective and well tolerated for sertraline-resistant depressive patients, which is accompanied with the increase in serum BDNF levels in responders to the risperidone addition, and the addition of risperidone to sertraline does not seem to influence sertraline metabolism.     

Faster onset of antidepressant effects of citalopram compared with sertraline in drug-naïve first-episode major depressive disorder in a Chinese population: a 6-week double-blind, randomized comparative study

Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-na?ve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-?sberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.     

Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study

The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.     

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.     

西酞普兰与米安色林治疗老年抑郁症的对照研究

目的比较西酞普兰与米安色林治疗老年抑郁症的疗效和不良反应。方法将60例老年抑郁症患者随机分为西酞普兰组和米安色林组。分别给予西酞普兰和米安色林治疗,疗程8周,采用汉密尔顿抑郁量表（HAMD）及不良反应量表（TESS）评定疗效和不良反应。结果西酞普兰组和米安色林组显效率分别为83.3%和80.0%,二者疗效相当。HAMD评分西酞普兰组第2周末显著下降,而米安色林组治疗第1周末即显著下降,不良反应方面,西酞普兰组以口干、恶心、出汗增多、头昏、睡眠时间缩短为主,米安色林组则以嗜睡、口干、便秘为主。结论西酞普兰和米安色林均为治疗老年抑郁症的安全有效的药物。