氢溴酸沃替西汀合成工艺改进

改进氢溴酸沃替西汀的合成工艺,以提高收率,简化处理过程。以2,4-二甲基苯硫酚和邻氯硝基苯为起始原料,经亲核取代、还原、缩合、成盐制得目标化合物。目标化合物经过1H-NMR,MS得到确证。该路线原料易得,后处理简单,反应条件温和,无需任何催化剂、缚酸剂。以2,4-二甲基苯硫酚计,总收率为57.3%,适合工业化生产。     

The impact of antidepressant treatments on family functioning in adults with major depressive disorder: a post hoc comparison of vortioxetine and agomelatine

Objective: There is limited research on the impact of antidepressant treatment on family functioning. This study examines the impact of vortioxetine and agomelatine on family functioning using the Depression and Family Functioning Scale (DFFS).

Methods: The DFFS was included in REVIVE, a randomized, double-blind study of adults with major depressive disorder with inadequate response to antidepressant treatment who switched to vortioxetine or agomelatine. The prespecified DFFS analyses were performed using change from baseline to weeks 8 and 12, analyzed by mixed models for repeated measurements by treatment groups. Post hoc analyses compared DFFS scores for remitters and nonremitters. Patients were stratified into quartiles using DFFS scores, and scores on other clinical outcome assessments were compared.

Results: Sizeable improvements in DFFS scores were observed from baseline to week 8 (?10.8, ?7.9 for vortioxetine and agomelatine, respectively), with further improvements at week 12 (?13.5, ?11.0). Vortioxetine (n?=?189) was superior to agomelatine (n?=?187) by 2.9 DFFS points at week 8 (p?p?n?=?142) and nonremitters (n?=?233) differed by 11 DFFS points; at week 12, remitters (n?=?183) and nonremitters (n?=?121) differed by almost 12 DFFS points. Patients stratified into baseline DFFS quartiles showed trends on clinical outcomes such that better family functioning was associated with better functional status and depressive symptoms.

Conclusions: Vortioxetine was significantly superior to agomelatine in terms of family functioning and partner relationships, as well as social functioning, health status, and depression symptoms at weeks 8 and 12. Depressed patients with impaired family functioning showed worse overall functioning, health status, and depression symptoms, suggesting that more attention should be given to family functioning of depressed patients.     

Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder

Abstract

Objective:

The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder.     

伏硫西汀与舍曲林治疗成人抑郁症的临床疗效对比

目的研究成人抑郁症患者行伏硫西汀、舍曲林治疗的效果。方法60例成人抑郁症患者,依双盲法分为对照组和观察组,每组30例。对照组予以舍曲林治疗,观察组予以伏硫西汀治疗。比较两组患者治疗前后汉密尔顿抑郁量表(HAMD)、威斯康星卡片分类测验(WCST)评分及治疗效果。结果治疗前,两组患者HAMD、WCST评分比较差异无统计学意义(P>0.05);治疗后,两组患者HAMD、WCST评分均明显低于本组治疗前,且观察组患者的HAMD、WCST评分均明显低于对照组,差异具有统计学意义(P<0.05)。观察组治疗总有效率96.67%明显高于对照组的76.67%,差异具有统计学意义(P<0.05)。结论伏硫西汀治疗成人抑郁症能提高疗效、缓解不适,值得推崇。     

Vortioxetine: a New Treatment for Major Depressive Disorder

Introduction: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug’s effects from those of current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

Areas Covered: This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE database literature search in August 2015 using the key search terms, vortioxetine and Lu AA21004, combined with additional terms that included pharmacological profile, pharmacokinetics, drug interactions, adverse effects, side effects, safety, major depression, and major depressive disorder. We identified relevant systematic reviews, meta-analyses, randomized trials and preclinical studies of importance.

Expert Opinion: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.     

Vortioxetine,a multimodal antidepressant for generalized anxiety disorder: A systematic review and meta-analysis

Vortioxetine has a beneficial pharmacological profile for reducing anxiety and depression. Recently, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with generalized anxiety disorder (GAD); however, the results from GAD RCTs are inconsistent. With an extensive search of databases and clinical trial registries, four published short-term RCTs were identified and included in the present meta-analysis. The mean change in total scores on the Hamilton Anxiety Rating Scale (HAMA) from baseline was the primary endpoint. The secondary endpoints included the response and remission rates, as defined by a ≥50% reduction in HAMA total scores and a ≤7 change in the HAMA total score at the end of treatment. In addition, the mean change in the HAMA total score from baseline in the subgroup with a HAMA total score ≥25 at baseline was included. Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of −0.118 (95% CIs, −0.203 to −0.033, P = 0.007). In particular, those with severe GAD (HAMA total score ≥25 at baseline) had a significantly greater benefit from vortioxetine than those without (SMD = −0.338, 95% CIs = −0.552 to −0.124, p = 0.002). The odds ratios (ORs) for vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P = 0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively. Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p = 0.047) was marginally higher in vortioxetine than placebo treatment, whereas discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly different among treatment groups. Although our results suggest that vortioxetine may have a potential as an another treatment option for GAD (especially for severe GAD), they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of RCTs.     

氢溴酸沃替西汀片溶出度测定方法学研究

目的 建立氢溴酸沃替西汀片的体外溶出度测定方法,分析体外释放行为。方法 建立高效液相色谱法测定氢溴酸沃替西汀片溶出度的方法,并考察方法的专属性、线性、精密度、准确性及滤膜干扰。Waters Symmetry C₁₈色谱柱（250mm×4.6 mm,5 μm）,以水/三氟乙酸混合溶液（1 000∶0.5）为流动相A,甲醇-乙腈-水-三氟乙酸混合溶液（600∶350∶50∶0.35）为流动相B,流动相A与流动相B比例为45∶55,体积流量1.0 mL/min,检测波长为254 nm,柱温40℃。结果 在上述色谱条件下,氢溴酸沃替西汀与其同分异构体分离良好。试验专属性、线性、精密度、准确性良好,所使用滤膜对结果测定无干扰。结论 该方法准确、可靠、耐用性好,可为氢溴酸沃替西汀片的质量控制提供参考依据。