Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial*

ABSTRACT

Objective: This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10?mg/day with sertraline optimally dosed within its recommended dose range (50–200?mg/day) for the treatment of major depressive disorder.

Methods: In this multicenter trial, depressed patients (DSM?IV defined; baseline Montgomery–Asberg Depression Rating Scale [MADRS] ≥ 22) aged 18–80 years were randomly assigned to 8 weeks of double-blind treatment with escitalopram (10?mg/day) or sertraline (50–200?mg/day) following a 1?week single-blind placebo lead-in period. There was no placebo comparison arm. Sertraline was initiated at 50?mg/day, and could be increased by 50?mg/day at weekly intervals based on clinical need and tolerability at the lower dose level. The blind was maintained with matching double-blind placebo capsules for the escitalopram group. Change from baseline to endpoint in MADRS total score (last observation carried forward) was the primary efficacy measure.

Results: A total of 212 patients received double-blind medication. At week 8, the mean sertraline dosage was 144?mg/day (median = 150?mg/day). Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups, respectively. At endpoint, 75% and 70% of escitalopram- and sertraline-treated patients, respectively, were responders (≥ 50% improvement from baseline in mean MADRS scores). Both treatments were generally well tolerated; only 2% and 4% of patients prematurely discontinued escitalopram and sertraline treatment, respectively, due to adverse events.

Conclusion: No differences in efficacy were observed for fixed-dose escitalopram 10?mg/day and sertraline flexibly dosed from 50–200?mg/day. At these doses, both escitalopram and sertraline were generally well tolerated.     

盐酸舍曲林的合成

目的简化盐酸舍曲林合成工艺,提高反应收率。方法对文献报道的盐酸舍曲林合成方法进行比较分析,设计一条比较合理的合成路线,用邻二氯苯和丁二酸酐做起始原料,通过两次傅-氏反应、手性拆分等五步反应合成盐酸舍曲林。结果产物经MS、IH—NMR、IR、元素分析确证了结构。结论与文献报道的路线相比,本研究较为详细考察了合成工艺,优化了合成路线,提高了反应收率。     

艾司西酞普兰与舍曲林治疗阿尔茨海默病伴发抑郁症状的对照研究

目的：比较艾司西酞普兰与舍曲林治疗阿尔茨海默病（AD）伴发抑郁症状的临床疗效和安全性。方法：60例伴发抑郁症状的诊断为AD的患者,随机分成两组,分别用艾司西酞普兰和舍曲林治疗6周。采用蒙哥马利-阿斯伯格抑郁评价量表（MADRS）,副反应量表（TESS）和简明智力状态检查（MMSE）于治疗前和治疗1、2、4、6周末分别评定疗效和不良反应。结果：艾司西酞普兰组有效率为70%,舍曲林组为63%,两组比较,无显著性差异（P〉0.05）,但艾司西酞普兰组起效快。两组药物有关的不良反应出现频率比较,无显著性差异（P〉0.05）。两者均不会加重AD患者的认知功能。结论：艾司西酞普兰和舍曲林治疗阿尔茨海默病伴抑郁症状疗效确切,服药依从性好,两组的不良反应均较轻微,两者不会加重AD患者的认知功能。艾司西酞普兰起效快,有望作为阿尔茨海默病伴发抑郁症状的一线用药。     

文拉法新与舍曲林治疗抑郁症疗效的Meta分析

目的：评价文拉法新与舍曲林治疗抑郁症疗效的差异。方法：对6项符合纳入标准的研究应用循证医学方法评价文拉法新与舍曲林治疗抑郁症疗效有效率、以及症状学变化的差异。结果：文拉法新组的有效率（122/177 vs 128/179,OR=1.22,95%CI：0.77~1.93,Z=0.86,P〉0.05）与曲林组相似,但是文拉法新组在第1周末（WMD：-1.57,95%CI：-2.98~-0.15,Z=2.17,P=0.03）和第2周末（WMD：-1.53,95%CI：-2.83~-0.23,Z=2.30,P=0.02）症状改善明显于舍曲林,而在第6周末相似（WMD：0.13,95%CI：-0.91~1.17,Z=0.25,P=0.81）。结论：文拉法新与舍曲林治疗抑郁症有效率相似,但前者症状改善前2周改善比较快。     

舍曲林与氯米帕明治疗难治性强迫症对照研究

目的探讨舍曲林与氯米帕明治疗难治性强迫症的疗效和不良反应。方法对难治性强迫症60例,随机分为两组,分别用舍曲林与氯米帕明治疗8周。采用强迫症量表（Y-BOCS）和副反应量表（TESS）评价疗效及不良反应。结果两药的总体疗效相仿。舍曲林不良反应小,尤其是心血管系统及抗胆碱能不良反应少。结论舍曲林尤适用于难治性强迫症。     

舍曲林与文拉法辛对首发抑郁症患者血清细胞因子水平影响的对照研究

目的 探讨首发抑郁症患者的细胞因子水平变化以及比较不同种类的抗抑郁剂舍曲林与文拉法辛对患者血清细胞因子水平的影响.方法 分别测定80例首发抑郁症患者的血清IL-2、IL-6、TNF-α、IL-10水平,并与40例健康对照者进行比较;80例首发抑郁症患者依抽签法分为人数相等的2组,分别经舍曲林、文拉法辛治疗6周后进行疗效评估,对舍曲林、文拉法辛治疗敏感的患者进行IL-2、IL-6、TNF-α、IL-10水平测定,并进行统计分析.结果 首发抑郁症患者的血清IL-2、IL-6、TNF-α细胞因子水平[(6.79±2.89)pg/ml,(10.12±4.52)pg/ml,(14.81±4.38)pg/ml]显著高于健康对照组[(4.06±2.05)pg/ml,(6.04±1.79)pg/ml,(10.69±2.54)pg/ml];舍曲林、文拉法辛治疗后较治疗前IL-6水平有显著降低(P＜0.05),IL-2、TNF-α、IL-10差异无显著性(P＞0.05),而舍曲林、文拉法辛两种抗抑郁剂对细胞因子水平的影响差异无显著性(P＞0.05).结论 首发抑郁症患者存在细胞因子水平的改变,并可以通过舍曲林、文拉法辛的治疗来矫正,而舍曲林、文拉法辛可能对细胞因子有相同的免疫作用机制.     

舍曲林和氯丙咪嗪治疗68例惊恐障碍的疗效比较

目的评价舍曲林治疗惊恐障碍的疗效和安全性。方法采用随机单盲病例对照研究,为期24周．以临床判断和PASS、HAMD、HAMA量表来评定临床效果,以TESS来评定药物不良反应。结果入组68例舍曲林组36例,氧丙味嗪组32例）．舍曲林组最高剂量平均132．5±25．25mg·d^-1。氯丙咪嗪组为153．62mg·d^-1．临床疗效。第四周末舍曲林有效率为77．7％,氯丙咪嗪组为65．6％．两组有统计学盖异（P〈0．05）,而二十四周末两组的有效率分别为100％和96．9％,两组无明显差异。从PASS、HAMD、HAMA量表来看舍曲林组从第二周末开培有明显下降,而氯丙咪嗪组则在第三或第四周以后才开始明显改变。从副反应来看舍曲林组总的发生率13．61%。明显低于氛丙味嗪组的24．68％。结论舍曲林治疗惊恐障碍和氯丙咪嗪比较具有起效快,疗效好。副作用小等特点。是一种安全有效的治疗惊恐障碍药物。     

Rapid analysis of sertraline,fluvoxamine, and paroxetine in serum specimens by LC-MS-MS using a new polymer column

Three selective serotonin reuptake inhibitors (sertraline, fluvoxamine, and paroxetine) in human serum specimens were analyzed by liquid chromatography-tandem mass spectrometry using a new polymer column (Shim-pack MAYI-ODS), which enabled direct injection of crude biological samples without complicated pretreatments. Quantitation was made by mass chromatography for each product ion using dextromethorphan as internal standard. The recoveries of the three drugs from human serum were 29.2%–45.7% at 20 ng/ml and 52.0%–53.7% at 80 ng/ml. The regression equations showed good linearity for the three drugs in the range of 5–80 ng/ml. Each drug had a detection limit of 1–3 ng/ml. Thus, the present method of using a new polymer column is effective for rapid and sensitive analysis of both therapeutic and toxic levels of sertraline, fluvoxamine, and paroxetine in biological specimens.     

持续口服小剂量西地那非治疗早泄

目的：评估持续口服小剂量西地那非治疗早泄的疗效。并比较佐洛复、百优解、癃闭舒治疗早泄的临床效果。方法：将152例早泄患者门诊随机归入4组，分别接受为期2个月的西地那非、佐洛复、百优解、癃闭舒治疗。在治疗前后记录各组患者CIPE（中国早泄指数评估表）评估分数及性伴侣对性生活的满意程度，比较治疗前后各组及各组间CIPE分数及满意度。结果：4组患者治疗前CIPE评分分别为（21．28±3．80）、（21．25±3．68）、（21．34±3．94）、（21．51±3．92）分，差异无统计学意义（P〉0．05）。治疗后CIPE评分分别为（38．83±4．85）、（33．10±5．07）、（33．51±5．03）、（28．23±5．40）分，差异有统计学意义（P〈0．01）。治疗后除百优解和佐洛复组间无明显差异外，其他各组间均差异有统计学意义（P〈0．05）。药物治疗后，各组夫妻性生活满意度明显改善，从高到低依次为：西地那非组、百优解组、佐洛复组、癃闭舒组。结论：每日口服小剂量西地那非能有效治疗早泄。在效果上，高于其他几种药物（P〈0．05），夫妻双方也有较好的满意度。     

The serotonin transporter polymorphism, 5HTTLPR,is associated with a faster response time to sertraline in an elderly population with major depressive disorder

Rationale A common polymorphism (5HTTLPR) within the promoter region of the serotonin transporter gene (LSC6A4) has been shown to influence response time as well as overall response to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder. We hypothesized that a similar effect in response time to sertraline would be observed and that no effect on response time would be seen in a placebo arm.Objectives We tested the hypothesis that subjects homozygous for the long allele at the 5HTTLPR polymorphism would respond more rapidly to sertraline than subjects carrying one or two copies of the short allele.Methods HAM-D and CGI-I responses to sertraline and placebo were measured weekly in the context of an 8-week, placebo-controlled study in elderly depressed subjects. Genotyping of the 5HTTLPR polymorphism was performed to test for correlations with response at each week in the sertraline and placebo groups (n=206).Results Subjects homozygous for the long allele of 5HTTLPR showed a significant increase in response at week 1 and week 2, as assessed by the CGI-I scale compared with subjects carrying one or two copies of the short allele (P=0.01 at both weeks). No significant difference was observed in the placebo group.Conclusions These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs.