中国汉族健康男性细胞色素P450酶2C19遗传多态性对艾司西酞普兰在人体内代谢的影响

目的评价中国汉族健康男性志愿者细胞色素P450（CYP450）2C19遗传多态性对艾司西酞普兰（抗抑郁症和惊恐障碍药）在人体内代谢的影响。方法16名志愿者单次口服艾司西酞普兰后，用PCR-测序法测定其CYP2C19基因的基因型，即野生基因型（＊1／＊1）含有1个突变基因组（＊1／＊2或＊1／＊3）及含有2个突变基因组（＊2／＊2，＊3／＊3或＊2／＊3）。用高效液相色谱-荧光检测法测定其血药浓度。比较艾司西酞普兰在CYP2C19不同基因型代谢的差异。结果随突变基因数目增多，血浆艾司西酞普兰AUC显著升高（P〈0．01），CLs显著降低（P〈0．01）。CLs、AUC0-t及AUC0-∞的差异在3组间表现出基因剂量效应倾向。结论CYP2C19遗传多态性是影响艾司西酞普兰药物代谢的重要因素。     

Heart rate variability and treatment outcome in major depression: A pilot study

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N = 26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N = 16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R² > .43 and p < 0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.     

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na⁺, K⁺ and Ca²⁺, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10^?9 M/L to 1.4 × 10^?6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10^?8 M/L, r = 0.580, P < 0.05) (F = 2.980, df₁ = 6, df₂ = 28, P < 0.05). Paroxetine (from 1.2 × 10^?9 M/L to 5.1 × 10^?5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10^?8 M/L, r = 0.500, P < 0.05) (F = 2.350, df₁ = 9, df₂ = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.     

Predicting escitalopram monotherapy response in depression: The role of anterior cingulate cortex

Neuroimaging biomarkers of treatment efficacy can be used to guide personalized treatment in major depressive disorder (MDD). Escitalopram is recommended as first‐line therapy for MDD and severe depression. An interesting hypothesis suggests that the reconfiguration of dynamic brain networks might provide important insights into antidepressant mechanisms. The present study assesses whether the spatiotemporal modulation across functional brain networks could serve as a predictor of effective antidepressant treatment with escitalopram. A total of 106 first‐episode, drug‐naïve patients and 109 healthy controls from three different multicenters underwent resting‐state functional magnetic resonance imaging. Patients were considered as responders if they had a reduction of at least 50% in Hamilton Rating Scale for Depression scores at endpoint (>2 weeks). Multilayer modularity framework was applied on the whole brain to construct features in relation to network dynamic characters that were used for multivariate pattern analysis. Linear soft‐threshold support vector machine models were used to separate responders from nonresponders. The permutation tests demonstrated the robustness of discrimination performances. The discriminative regions formed a spatially distributed pattern with anterior cingulate cortex (ACC) as the hub in the default mode subnetwork. Interestingly, a significantly larger module allegiance of ACC was also found in treatment responders compared to nonresponders, suggesting high interactivities of ACC to other regions may be beneficial for the recovery after treatment. Consistent results across multicenters confirmed that ACC could serve as a predictor of escitalopram monotherapy treatment outcome, implying strong likelihood of replication in the future.     

艾司西酞普兰与帕罗西汀治疗抑郁症伴焦虑症状对照研究

目的 探讨艾司西酞普兰与帕罗西汀治疗抑郁症伴焦虑症状的临床疗效及安全性.方法将52例抑郁症伴焦虑症状患者随机分为两组,每组26例,研究组口服艾司西酞普兰治疗,对照组口服帕罗西汀治疗,观察6周.于治疗前及治疗1周、2周、4周、6周末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 治疗后两组汉密顿抑郁量表总分及焦虑/躯体化因子分均较治疗前显著下降(P<0.01),研究组治疗2周末均较对照组下降更显著(t=3.21,2.52,P<0.01);治疗6周末,研究组总有效率88.46%,对照组为84.62%,两组差异无显著性(X2=0.118,P>0.05).两组不良反应均轻微.结论 艾司西酞普兰与帕罗西汀治疗抑郁症伴焦虑症状疗效显著,总体疗效相当,安全性高,依从件好,但艾司西酞普兰起效更快,可作为治疗抑郁症伴焦虑症状的首选药物.     

艾司西酞普兰与帕罗西汀治疗老年性抑郁症的效果比较

目的 比较艾司西酞普兰与帕罗西汀治疗老年性抑郁症的效果.方法 将2017年2月1日至2019年2月1日收治的98例老年性抑郁症患者按随机数字表法分为A组和B组,每组49例.A组患者予以艾司西酞普兰治疗,B组患者予以帕罗西汀治疗,比较两组的治疗效果.结果 两组的治疗总有效率比较,差异无统计学意义(P>0.05).治疗2周...     

艾司西酞普兰与氟西汀治疗抑郁症对照研究

目的探讨艾司西酞普兰与氟西汀治疗抑郁症的临床疗效和安全性。方法将65名抑郁症患者随机分为两组,研究组33例,口服艾司西酞普兰治疗,对照组32例,口服氟西汀治疗,观察6周。于治疗前及治疗第1周、2周、4周、6周末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。结果治疗后两组汉密顿抑郁量表总分均较治疗前有显著下降（P〈0．01）,研究组治疗第2周末较对照组下降显著（P〈0．01）。治疗6周末,研究组显效率78．78％,有效率90．91％;对照组分别为75．00％、87．50％,两组疗效无显著性差异（P〉0．05）。两组不良反应均轻微,随着治疗时间的延长均可减轻或缓解。结论艾司西酞普兰与氟西汀治疗抑郁症总体疗效显著且相当,安全性高、依从性好,但艾司西酞普兰起效更快。     

艾司西酞普兰联合睡眠剥夺疗法治疗产后抑郁症对照研究

目的探讨艾司西酞普兰联合睡眠剥夺疗法治疗产后抑郁症的临床疗效。方法将49例产后抑郁症患者随机分为两组,研究组25例,对照组24例,两组均口服艾司西酞普兰治疗,研究组在此基础上联合睡眠剥夺疗法治疗,观察6周。于治疗前及治疗1周、2周、4周、6周末采用汉密顿抑郁量表评定临床疗效。结果治疗后两组汉密顿抑郁量表总分均较治疗前有显著性下降（P〈0．01）,但同期研究组均较对照组下降更显著（P〈0．01）。两组不良反应均较轻微且无显著性差异,主要表现为口干、失眠、恶心等。结论艾司西酞普兰联合睡眠剥夺疗法治疗产后抑郁症可显著增加抗抑郁效果,较单用艾司西酞普兰治疗起效更快,疗效更显著,安全性高,依从性好。     

Comparison of Toxicity of Acute Overdoses with Citalopram and Escitalopram

Background: Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. Objectives: The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. Methods: A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002–2005. Results: There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68–70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p < 0.001). Most frequently reported clinical effects with citalopram and escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p < 0.001) and tremor (32 vs. 13, respectively, p = 0.001) were more common with citalopram. QTc prolongation occurred in 14 citalopram cases and 7 escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p < 0.001) and escitalopram (p = 0.011). In children < 6 years old, 12 of 66 citalopram and 5 of 57 escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Conclusions: Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs.