米氮平与舍曲林治疗抑郁症伴有焦虑疗效比较

目的 :比较米氮平与舍曲林对抑郁症伴焦虑的疗效及其安全性。方法 :1 1 1例抑郁症分为 2组。米氮平组 56例 [男性 30例 ,女性 2 6例 ,年龄(39±s 1 3)a,本次抑郁病期 (3± 5)mo]予米氮平30～ 45mg ,po,qd;舍曲林组 55例 [男性 2 9例 ,女性 2 6例 ,年龄 (40± 1 2 )a,本次抑郁症病期 (4± 4)mo]予舍曲林 50～ 1 0 0mg,po,qd;均 6wk为一个疗程。结果 :对抑郁症状的治疗 ,米氮平组显效率73 % ,舍曲林组显效率 67% ,疗效差异无显著意义(P >0 .0 5) ;对焦虑症状的治疗 ,米氮平组显效率79 % ,舍曲林组显效率 44 % ,疗效差异有显著意义(P <0 .0 5)。整体药物不良反应发生率 2组相当。结论 :米氮平与舍曲林是安全有效的治疗抑郁症的药物 ,但抗焦虑作用米氮平优于舍曲林     

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.     

Influence of liver cirrhosis on sertraline pharmacokinetics

Sertraline is a serotonin reuptake inhibitor. The enhancement of serotoninergic transmission is associated with antidepressant activity. In order to determine the pharmacokinetics of sertraline in patients with chronic stable hepatic insufficiency, 10 patients were matched (age, weight, sex) with 10 healthy subjects in an open study. Each participant received a single capsule containing the equivalent of 100  mg sertraline base. Blood samples were taken during 264  h after administration for measurement of plasma concentrations of sertraline. The results confirm that the oral clearance of sertraline is reduced with a 1.7-fold increase in C _max and a significant prolongation in elimination half-life in hepatically impaired patients     

The pharmacokinetics of sertraline in overdose and the effect of activated charcoal

Aims

To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).

Methods

Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose.

Results

There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250–5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h⁻¹, 5340 l and 130 l h⁻¹, respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4−30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (C_max).

Conclusions

Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.     

Selective serotonin reuptake inhibitors for migraine prophylaxis

The objective of this study was to assess the efficacy of sertraline in migraine prophylaxis. Other selective serotonin reuptake inhibitors have been studied for migraine prophylaxis, but this is the first report with sertraline. Twenty-seven subjects were enrolled and baseline assessment of migraine frequency and severity were measured over a 4-week period. Subjects were then randomized to receive placebo or sertraline in a double-blind fashion with headache frequency and severity measured over an 8-week period. Subjects completed a daily diary reporting the occurrence, severity, and degree of impairment associated with migraine.
The headache index, a composite measure of migraine frequency and severity, scores did not significantly improve between assessments at baseline (20.8 ± 14.88), 8 weeks (17.6 ± 12.27), and 12 weeks (16.7 ± 6.38) in the treatment group (n=6) ( P =0.956). This finding is compared to other studies with the serotonin selective reuptake inhibitors, fluoxetine, fluvoxamine, and paroxetine. The authors believe that the selective serotonin reuptake inhibitors are not as effective as conventional migraine prophylaxis medications such as β-blockers, tricyclic antidepressants, or divalproex sodium, but that in patients with comorbid depression who have failed conventional therapy selective serotonin reuptake inhibitors may be effective.     

Parkinsonism and Parkinson's disease associated with long-term administration of sertraline

Sertraline, a serotonin reuptake inhibitor, has been used to treat depression and has rarely been associated to Parkinsonism. The disease usually appears in old people a few days after sertraline administration and disappears very quickly after its withdrawal. We report a case of a woman, 81-year-old, who presented with hemiparkinsonism after long-term administration of sertraline at a dose of 100 mg/day. The symptoms disappeared 3 months after the withdrawal of the drug. However, without further administration of the drug for 14 months, the patient presented with Parkinson's disease, but responded well to levodopa.     

舍曲林对阿立哌唑治疗阴性症状为主精神分裂症的增效作用

目的探讨阿立哌唑联合舍曲林治疗阴性症状为主的精神分裂症的疗效与安全性。方法将120例阴性症状为主的精神分裂症患者随机分入试验组和对照组,每组60例,试验组采用阿立哌唑和舍曲林片口服治疗,而对照组只采用阿立哌唑口服治疗。观察治疗12周,用阳性与阴性综合征量表（PANSS）和副反应量表评定临床疗效和安全性。结果在治疗后第8、12周末,试验组临床疗效优于对照组（Z分别=-2.11、-2.03,P均＜0.05）。在治疗后第2、4、8、12周末,试验组PANSS（阳性症状除外）评分均低于对照组（t分别=-4.39、-2.25、-4.71;-6.44、-4.36、-6.87;-5.12、-2.61、-4.89;-4.03、-2.63、-4.61,P均＜0.05）。除了阳性症状外,不同干预手段、不同时间及两者交互效应对于PANSS评分中的阴性症状、精神病理及总分结果均有明显影响（P均＜0.05）。 TESS评分组间比较,差异均无统计学意义（t分别=-0.43、1.58、1.21、1.59、1.70,P均＞0.05）。结论舍曲林联合阿立哌唑治疗阴性症状为主精神分裂症有明显的增效作用,不良反应未见明显增加。     

舍曲林联合重复经颅磁刺激治疗难治性抑郁症对照研究

目的 探讨抗抑郁剂联合重复经颅磁刺激治疗难治性抑郁症的临床疗效及安全性.方法将88例难治性抑郁症患者随机分为实验组45例,对照组43例,两组均口服舍曲林100 mg·d.治疗,实验组联合重复经颅磁刺激治疗,对照组联合无抽搐电休克治疗,观察4周.于治疗前及治疗4周末采用汉密顿抑郁量表评定临床疗效,并记录起效时间、脱落率、...     

舍曲林联合喹硫平治疗难治性抑郁症对照研究

目的 探讨舍曲林联合喹硫平治疗难治性抑郁症的临床疗效和安全性.方法 将58例难治性抑郁症患者随机分为两组,每组29例.两组均口服舍曲林治疗,在此基础上研究组联合喹硫平治疗,观察12周.于治疗前及治疗1周、2周、4周、6周、12周末采用汉密顿抑郁量表及汉密顿焦虑量表评定临床疗效,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及汉密顿焦虑量表评分均较治疗前有显著性下降(P＜0.01),同期研究组均较对照组下降显著(P＜0.05或0.01);治疗12周末,研究组有效率65.5%,对照组为37.9%,研究组显著高于对照组(χ2=4.419,P＜0.05).研究组不良反应发生率为41.4%,对照组为34.5%,两组不良反应程度均较轻,同期副反应量表评分差异无显著性(P＞0.05).结论喹硫平对治疗难治性抑郁症具有增效作用;舍曲林联合喹硫平治疗难治性抑郁症疗效显著,起效快,安全性高,依从性好,显著优于单用舍曲林治疗.