Forced swim test behavior in postpartum rats

This study was undertaken to determine whether depression-like behavior can be observed in gonadally intact females that have experienced normal pregnancy. When tested on the forced swim test (FST) on postpartum days 1-7, previously pregnant rats spent slightly more time immobile, significantly less time swimming and diving, and defecated more than virgin controls. Subchronic treatment with nomifensine (DA reuptake inhibitor, 2.5 mg/kg) but not sertraline (serotonin reuptake inhibitor, 10 mg/kg) or desipramine (norepinephrine reuptake inhibitor, 10 mg/kg) significantly decreased immobility on postpartum day 2. In rats pre-exposed to the FST in mid-pregnancy, neither subchronic nor chronic treatment with desipramine or sertraline decreased immobility on postpartum day 2; in contrast, chronic desipramine significantly decreased immobility in virgin controls. These results indicate that postpartum female rats, compared to virgin controls, show a reduction in some “active coping behaviors” but no significant increase in immobility when tested during the early postpartum period, unlike ovariectomized females that have undergone hormone-simulated pregnancy (HSP). Additionally, immobility that is increased by FST pre-exposure is not readily prevented by treatment with standard antidepressant medications in postpartum females. Depression-like behaviors previously observed in females that have undergone HSP may result from the more dramatic changes in estradiol, prolactin or corticosterone that occur during the early “postpartum” period, compared to the more subtle changes in these hormones that occur in actual postpartum females.     

中西医结合治疗卒中后抑郁疗效观察

目的 观察加味半夏厚朴汤联合舍曲林对脑卒中后抑郁(PSD)的临床疗效.方法 将90例卒中后抑郁患者根据治疗方法分为治疗组45例与对照组45例,均服用舍曲林,治疗组加服加味半夏厚朴汤.结果 治疗6周后两组患者HAMD评分均较治疗前有明显降低(P＜0.05),治疗组显著优于对照组(P＜0.05);治疗后两组患者疗效均较治疗前有明显提高,治疗组明显优于对照组(P＜0.05).结论 中西医结合治疗卒中后抑郁更有优势.     

Cost–utility comparison of escitalopram and sertraline in the treatment of major depressive disorder

ABSTRACT

Objective: To construct a cost–utility model comparing escitalopram with sertraline in the treatment of major depressive disorders.

Methods: A decision analytic model was created to compare the cost–utility of these two antidepressants from the perspective of a managed-care organization. The model was designed to compare 10–20?mg/day of escitalopram to 50–200?mg/day of sertraline. Benefits (utility) scores were calculated based on clinical and utility data obtained from the literature. Direct medical costs included costs of the antidepressants, titration, treatment failures, and adverse events. Costs and benefits were modeled for a 6-month period and the model was subjected to thorough sensitivity analyses.

Results: The estimated 6-month total cost was $919 for escitalopram and $1351 for sertraline. The estimated QALYs were 0.40296 for escitalopram and 0.39268 for sertraline. These differences were mostly due to differences in drug acquisition costs and adverse events. The robustness of the cost–utility model results were tested in a Monte Carlo simulation of 10?000 patients and it indicated an 88.5% probability that escitalopram was the dominant therapy, suggesting both lower costs and greater QALYs.

Conclusion: This cost–utility model that incorporated the costs of titration and impact of side-effects comparing escitalopram 10–20?mg per day and sertraline 50–200?mg per day shows that escitalopram appeared to be less costly and produced efficacy (utility) at least as good as and maybe slightly better than that of sertraline.     

米氮平和舍曲林对抑郁症血糖影响的对照研究

目的 探讨米氮平对抑郁障碍患者空腹血糖(FBG)的影响.方法 将93例抑郁障碍患者采用随机数字表法随机分为米氮平组、米氮平联合舍曲林组(以下简称联合用药组)、舍曲林组,每组31例;治疗观察期均为12周;3组患者于治疗前及治疗后第4、8、12周末测定FBG进行比较.结果 米氮平组与联合用药组间FBG的差异无统计学意义(P＞0.05),而此上述2组FBG均高于舍曲林组,差异有统计学意义(P均＜0.05);米氮平组和联合用药组基线与第4周末FBG比较,差异无统计学意义(P均＞0.05),而基线与第8周末或第12周末比较,差异有统计学意义(P均＜0.05);舍曲林组基线与第4、8、12周末FBG比较,差异无统计学意义(P均＞0.05);3组间在第4周末或第8周末出现空腹血糖过高(IFG)频率的差异无统计学意义(P均＞0.05),而在第12周末,米氮平组或联合用药组与舍曲林组间出现IFG频率的差异有统计学意义(P均＜0.05).结论 米氮平单一或联合舍曲林治疗既往无糖代谢异常的抑郁障碍患者可出现有临床意义的IFG,且IFG出现的频率可能有随时间延长而增加的趋势.     

舍曲林与帕罗西汀治疗强迫症的对照研究

目的 比较舍曲林与帕罗西汀治疗强迫症的疗效及安全性。方法 分别用舍曲林和帕罗西汀治疗强迫症患者各36例，采用Yale—Brown强迫量表、汉密尔顿抑郁量表（HAMD）及副反应量表（TESS）评定疗效和不良反应。结果 舍曲林和帕罗西汀疗效相似，差异无显著性，舍曲林起效慢于帕罗西汀，其副反应也少于帕罗西汀。结论 舍曲林治疗强迫症安全有效，值得推广。     

Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients

Objective  To investigate the impact of CYP2C19 genotype on serum concentrations of sertraline and N-desmethyl sertraline in psychiatric patients. Methods  Patients treated with sertraline (n = 121) were divided into six subgroups according to CYP2C19 genotype: CYP2C19*17/*17, CYP2C19*1/*17, CYP2C19*1/*1, CYP2C19*17/def, CYP2C19*1/def and CYP2C19def/def (def = allele encoding defective CYP2C19 metabolism, i.e. *2 and *3). Dose-adjusted serum concentrations were compared by linear mixed model analyses using the CYP2C19*1/*1 subgroup as reference. Results  Subgroups carrying one or two alleles encoding defective CYP2C19 metabolism achieved significantly higher mean dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline compared to the CYP2C19*1/*1 subgroup (P < 0.05). The effect of CYP2C19 genotype was expressed as 3.2-fold (sertraline) and 4.5-fold (N-desmethyl sertraline) higher dose-adjusted serum concentrations in the CYP2C19def/def subgroup compared to the CYP2C19*1/*1 subgroup (P < 0.01). The CYP2C19*17 allele had no influence on the dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline. Conclusion  The significantly higher serum concentrations associated with alleles encoding defective CYP2C19 metabolism might be of relevance for the clinical outcome of sertraline treatment.     

人参果总皂苷(SFPG)联合舍曲林治疗高血压病合并抑郁症的疗效及副反应观察

摘要 目的 探讨人参果总皂苷(SFPG)联合舍曲林治疗高血压病合并抑郁症的临床疗效及安全性。方法 选取88例高血压病合并抑郁症患者随机分为SFPG加舍曲林组和舍曲林单用组,在治疗前和用药后2,4,6周用HAMD评分量表评定其疗效,以TESS量表评定并观察两者的副作用。结果 治疗6周末,与舍曲林单用组相比,联合组HAMD评分的减分率有显著性差异,且不良反应明显减少(P<0. 01) ,合用组有效率为93.00%,单用组有效率为77.80%,两比较差异有显著性(P<0. 01)。两组患者用药6周TESS评分比较有显著性差异 (P<0. 01)。结论 SFPG对高血压病合并抑郁症的治疗有显著的辅助作用,副反应较单用舍曲林减少。     

Characterization of -fenfluramine-induced hypothermia: evidence for multiple sites of action

The effects of -fenfluramine on core body temperature has been largely investigated under conditions of either high or low ambient temperature, whereas little research has focused on this response under normal environmental conditions. Moreover, there has been neglect in research on the mechanisms underlying changes in body temperature. In this study, we demonstrate that -fenfluramine (5 and 10 mg/kg) induces a sustained decrease in body temperature in the rat under normal ambient temperatures. Pre-treatment with the selective serotonin reuptake inhibitor sertraline (5 mg/kg), the full 5-HT_1A receptor antagonist 4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2-pyridinyl benzamide], WAY 100635 (0.15 mg/kg) and the 5-HT_2C receptor antagonist benzofuran-2-carboxamidine, RO 43-0440 (2.5 mg/kg) blocked -fenfluramine-induced hypothermia. Depletion of 5-hydroxytryptamine (5-HT) stores following treatment with the serotonergic neurotoxin parachlorophenylalanine reversed the initial hypothermic effects of -fenfluramine but not the later effects, as -fenfluramine produced a delayed hypothermia (>120 min post-challenge) in animals pre-treated with parachlorophenylalanine. Such findings are consistent with a requirement for -fenfluramine uptake into 5-HT neurons followed by release of 5-HT from intracellular stores and stimulation of post-synaptic 5-HT receptors to reduce body temperature. The hypothermic response to -fenfluramine was potentiated by ketanserin pre-treatment 30 min post-challenge but then antagonized at later time intervals. Pre-treatment with the dopamine, D₂ antagonist, haloperidol (1 mg/kg) and sulpiride (30 mg/kg) had a similar effect in blocking the hypothermia as WAY 100635, suggesting a role for dopamine D₂ receptors in the response. Pre-treatment with the α₂-adrenoceptor antagonist yohimbine failed to block the hypothermic response. These results suggest multiple sites of action mediating -fenfluramine-induced hypothermia and may be the result of a combined effect of -fenfluramine and its active metabolite norfenfluramine affecting not only the release of 5-HT but also stimulation of post-synaptic receptors.     

利培酮联合舍曲林治疗精神分裂症阴性症状 疗效和安全性的Meta分析

目的 系统评价利培酮联合舍曲林治疗精神分裂症阴性症状的疗效和安全性。方法 计算机检索PubMed、EMbase、The Cochrane Library、CBM、WanFang Data和CNKI数据库,搜集有关利培酮联合舍曲林治疗精神分裂症阴性症状疗效和安全性的随机对照试验（RCT）,检索时限从2007年1月~2017年9月。由两位评价员独立筛选文献、摄取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果 最终纳入10个RCT,包括703个患者。Meta分析结果显示:与单用利培酮相比,利培酮联合舍曲林能明显提高有效率[RR=1.39,95%CI（1.26,1.54）,P＜0.00001],降低阳性与阴性统计量表（PANSS）总分[SMD=-0.46,95%CI（-0.69,-0.22）,P=0.0001]及其阴性分[SMD=-0.73,95%CI（-0.98,-0.49）,P＜0.00001],降低阴性症状量表（SANS）评分[SMD=-0.67,95%CI（-0.91,-0.43）,P＜0.00001];对集中报道的不良反应（失眠、视物模糊,锥外体系反应、口干）发生率进行比较,差异无统计学意义（P＞0.05）。结论 利培酮联合舍曲林能提高对精神分裂症阴性症状的疗效,并不增加不良反应发生率。受纳入研究质量的限制,上述结论尚需开展更多高质量的研究予以验证。