艾司西酞普兰与西酞普兰治疗抑郁症对照观察

目的：探讨艾司西酞普兰与西酞普兰治疗抑郁症的临床疗效及安全性。方法将60例抑郁症患者按就诊顺序随机分为艾司西酞普兰组和西酞普兰组,每组30例,分别口服艾司西酞普兰、西酞普兰治疗,观察6周。于治疗前后采用汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果治疗第6周末艾司西酞普兰组总有效率为86.67%,西酞普兰组为83.33%,两组比较差异无显著性(P >0.05)。艾司西酞普兰组治疗第1周末起,西酞普兰组治疗第2周末起汉密顿抑郁症量表总分较治疗前显著降低(P <0.01);治疗第1周末艾司西酞普兰组显著低于西酞普兰组(P <0.01),其他治疗时点两组比较差异无显著性(P >0.05)。艾司西酞普兰组不良反应发生率为43.3%,西酞普兰组为50.0%,两组比较差异无显著性(P >0.05)。结论艾司西酞普兰治疗抑郁症疗效显著,安全性高,与西酞普兰相当。     

艾司西酞普兰治疗冠心病支架植入术患者伴发焦虑抑郁情绪对照研究

目的：探讨放松训练联合草酸艾司西酞普兰对冠心病支架植入术后患者伴发焦虑抑郁情绪的临床疗效和安全性以及对生活质量的影响。方法将65例冠心病冠脉支架植入术后伴焦虑抑郁患者随机分为两组,均予以冠心病常规治疗及放松训练,研究组在此基础上联合草酸艾司西酞普兰治疗,观察8周。采用汉密顿焦虑量表、汉密顿抑郁量表评定焦虑抑郁情绪,生活质量量表评定生活质量,副反应量表评定不良反应。结果治疗后两组汉密顿焦虑量表、汉密顿抑郁量表评分较治疗前显著下降（P＜0．01）,研究组较对照组下降更显著（P＜0．01）;研究组生活质量量表的4个领域、对照组1个领域评分较治疗前显著升高（P＜0．01）,研究组5个领域评分显著高于对照组（P＜0．01）。治疗过程中两组不良反应均轻微,各项实验室检查均无异常改变。结论放松训练联合草酸艾司西酞普兰能显著改善冠心病冠脉支架植入术患者伴发的焦虑抑郁情绪,提高患者的生活质量,且安全性高,优于单用放松训练治疗。     

心理干预与艾司西酞普兰治疗轻中度抑郁发作对照研究

目的：探讨心理干预与艾司西酞普兰治疗轻中度抑郁发作的临床疗效。方法将120例轻中度抑郁发作患者随机分为两组,研究组（58例）予以心理干预,对照组（62例）口服艾司西酞普兰治疗,治疗过程中脱落病例进入脱落治疗组,予以心理干预联合艾司西酞普兰治疗,观察24周。于治疗前后采用汉密顿抑郁量表评定临床疗效。结果治疗初期研究组脱落率为36．2％,对照组为12．9％,研究组脱落率显著高于对照组（ P＜0．01）。治疗后研究组与对照组汉密顿抑郁量表评分均较治疗前显著下降（ P＜0．05或0．01）,对照组治疗2周、8周、12周末较研究组下降更显著（ P＜0．05或0．01）,治疗24周末研究组与对照组总有效率均显著高于脱落治疗组（P＜0．01）,研究组与对照组比较差异无显著性（P＞0．05）。结论心理干预治疗轻中度抑郁发作虽起效较缓慢,但远期治疗效果显著,与艾司西酞普兰疗效相当。     

草酸艾司西酞普兰联合健脑宁口服液治疗抑郁症对照研究

目的：探讨草酸艾司西酞普兰联合健脑宁口服液治疗抑郁症的临床疗效和安全性。方法将100例抑郁症患者随机分为两组,每组50例,均口服草酸艾司西酞普兰治疗,研究组联合健脑宁口服液治疗,观察4周。于治疗前后采用汉密顿焦虑量表、汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果治疗4周末两组汉密顿焦虑量表、汉密顿抑郁量表总分均较治疗前显著性下降（P＜0．01）,研究组较对照组下降更显著（P＜0．05或0．01）;研究组有效率为98．0％,对照组为88．0％,研究组有效率显著高于对照组（ P＜0．05）。两组不良反应主要表现为口干、兴奋、头昏、便秘等,发生率比较差异无显著性（χ2＝2．64,P＞0．05）。结论草酸艾司西酞普兰联合健脑宁口服液治疗抑郁症具有增效作用,且不增加不良反应,安全性高,优于单用艾司西酞普兰治疗。     

Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men

Background:

Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV).

Methods:

The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application.

Results:

Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; _pη² = 0.499), SDNN (p < 0.001; _pη² = 576), RMSSD (p = 0.015; _pη² = 194), NN50% (p = 0.008; _pη² = 0.224), and LF% (p = 0.014; _pη² = 0.196), and moderate effects with respect HF% (p = 0.099; _pη² = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response.

Conclusions:

Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.     

Treatment of cannabis dependence using escitalopram in combination with cognitive-behavior therapy: a double-blind placebo-controlled study

Background: Cannabis is the most frequently used illegal substance in the United States and Europe. There is a dramatic increase in the demand for treatment for cannabis dependence. Cannabis users frequently have co-morbid mood symptoms, especially depression and anxiety, and regular cannabis users may self-medicate for such symptoms. Objectives: We report a double-blind, placebo-controlled treatment study, for the prevention of cannabis use in cannabis-dependent individuals. Method: Regular cannabis-dependent users (n?=?52) were treated for 9 weeks with weekly cognitive-behavior and motivation-enhancement therapy sessions together with escitalopram 10?mg/day. Urine samples were collected to monitor delta-9 tetrahydrocannabinol (THC) during treatment and questionnaires were administered to assess anxiety and depression. Results: We observed a high rate of dropout (50%) during the 9-week treatment program. Fifty-two patients were included in the intention-to-treat analysis. Of these, ten (19%) remained abstinent after 9 weeks of treatment as indicated by negative urine samples for THC. Escitalopram provided no advantage over placebo in either abstinence rates from cannabis or anxiety and depression scores during the withdrawal and abstinent periods. Conclusions: Escitalopram treatment does not provide an additional benefit either for achieving abstinence, or for the treatment of the cannabis withdrawal syndrome. Due to limitations of our study, namely, a high dropout rate and effects of low abstinence rates on measures of anxiety, depression and withdrawal, it is premature to conclude that selective serotonin reuptake inhibitors are not effective for treatment of the cannabis withdrawal syndrome.     

Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.     

艾司西酞普兰合并托吡酯治疗男性酒依赖伴焦虑抑郁及复饮

目的 探讨艾司西酞普兰合并托吡酯对男性酒依赖患者伴有焦虑抑郁的临床疗效、安全性及对复饮的影响。方法 采用了随机、对照的临床试验设计,把入组的患者分成艾司西酞普兰合并托吡酯治疗组(协同用药组)和单用艾司西酞普兰治疗组(单一用药组)。共治疗了12周,治疗前后分别采用了汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、用药后出现的不良反应量表(TESS)、可视渴求量表(VAS)等评估患者的临床效果及安全性。结果 2组HAMA、HAMD评分在治疗后4周末、8周末与治疗前比较差异有统计学意义(P<0.05)。随着治疗时间的延长2组VAS评分均逐渐下降,协同用药组渴求程度下降更为明显(P<0.05);协同用药组在随访6个月时复饮率低于单一用药组,差异有统计学意义(χ²=11.009,P=0.001<0.05);2组用药后不良反应发生率的差异无统计学意义(P>0.05)。结论 对伴焦虑抑郁症状的酒依赖患者,艾司西酞普兰合并托吡酯治疗焦虑、抑郁症状的疗效与单用艾司西酞普兰相当,但减少对酒的渴求优于单用艾司西酞普兰,且患者有更低的复饮率。2种治疗方案的不良反应相当。     

Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations

Aims

Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT.

Methods

Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects.

Results

Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10⁻⁹) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10⁻¹⁶), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation.

Conclusions

In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors.     

艾司西酞普兰添加治疗对帕金森病患者非运动症状的临床疗效

目的：考察普拉克索添加艾司西酞普兰治疗对帕金森病患者非运动症状的临床疗效。方法：将60例帕金森病患者按收治顺序单双号分为观察组和对照组,每组30例。对照组采用口服盐酸普拉克索治疗,观察组则在口服盐酸普拉克索基础上添加艾司西酞普兰治疗,连续治疗8周后,分别以帕金森病综合评分量表（UPDRS）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）、匹兹堡睡眠质量指数（PQSI）和生活质量综合评定量表（GQOLI-74）的评分为指标,对比考察2组患者的综合症状、抑郁和焦虑症状、睡眠和生活质量等的变化。结果 ：与治疗前相比,2组患者治疗后,UPDRS总分、运动检查以及精神、行为和情感评分均显著降低（P〈0.05）,治疗并发症和日常生活评分无显著差异（P〉0.05）,其中观察组患者的UPDRS总分以及精神、行为和情感评分较对照组显著降低（P〈0.05）,而2组患者的治疗并发症、日常生活和运动检查评分无显著差异（P〉0.05）;且2组患者治疗后,HAMD、HAMA和PQSI评分均显著降低（P〈0.05）,其中观察组患者的HAMD、HAMA和PQSI评分较对照组显著降低（P〈0.05）,而2组患者的GQOLI-74评分均显著升高（P〈0.05）,其中观察组患者GQOLI-74评分显著高于对照组（P〈0.05）。结论 ：普拉克索添加艾司西酞普兰治疗可有效改善帕金森病患者抑郁、焦虑、睡眠障碍等非运动症状,从而提高患者生活质量,具有重要的临床意义。