伏硫西汀与文拉法辛治疗抑郁症临床研究

目的 探讨伏硫西汀治疗抑郁症的临床疗效及安全性.方法 将113例抑郁症患者按随机数字表法分为伏硫西汀组59例和文拉法辛组54例.伏硫西汀组给予伏硫西汀治疗,文拉法辛组予以文拉法辛治疗,观察8周.于治疗前后采用临床疗效总评量表评定临床疗效,汉密顿抑郁量表总分及认知障碍因子评定疾病严重程度及认知功能,副反应量表评定不良反应...     

Clinical Switching Strategies of Various Antidepressants to Vortioxetine in the PREDDICT Trial

BackgroundPartial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib.MethodsWe describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine.ResultsOf a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4.ConclusionChanging other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR); ID number 12617000527369p; http://www.anzctr.org.au/ACTRN12617000527369p.aspx     

HPLC-MS/MS法对氘代沃替西汀氢溴酸盐及其代谢物的检测及大鼠血浆毒代动力学研究

目的:利用HPLC-MS/MS建立大鼠血样中氘代沃替西汀氢溴酸盐(代号JJH201501)及其代谢物(代号JJH201501-01)的检测方法,考察重复给药毒代动力学研究.方法:采用Poroshe11120 EC-C18(4.6 mm × 50 mm,2.7μm),以0.1％甲酸(A)-甲醇(B)为流动相,梯度洗脱,流...     

LC-MS/MS法测定大鼠血浆中沃替西汀及其羧基代谢产物

本试验建立了大鼠血浆中沃替西汀及其体内羧基代谢物的LC-MS/MS测定方法,并用该法研究其在SD大鼠体内的药动学特征。以氘代沃替西汀为内标,血浆样品经蛋白沉淀法处理后进样测定,色谱柱为Kromasil■C18柱,以含0.1%甲酸的10 mmol/L甲酸铵水溶液(A)∶甲醇(B)为流动相,梯度洗脱,流速为0.3 ml/min,分析时间5 min。采用电喷雾离子源(ESI)、正离子检测、多反应监测模式,沃替西汀及其羧基代谢产物定量离子对分别为m/z 299.1→150.1和m/z329.2→286.3,内标氘代沃替西汀离子对为m/z 302.3→150.0。沃替西汀线性范围为0.3~100.0 ng/ml(r=0.998 6),羧基代谢物线性范围为0.9~300.0 ng/ml(r=0.999 2)。沃替西汀及其羧基代谢物的批内和批间RSD均小于15%。SD大鼠单次口服6 mg/kg沃替西汀后,沃替西汀及其羧基代谢物的t1/2为(2.66±0.35)和(1.76±0.19)h,cmax为(18.60±5.34)和(309.00±84.10)μg/L,AUC0→t为(123.0±28.9)和(1 165.0±236.0)μg·h·L-1。本法快速简便、灵敏准确,适用于沃替西汀及其羧基代谢物的血药浓度测定及药动学研究。     

抗抑郁新药沃替西汀的药理与临床研究

沃替西汀(vortioxetine)临床用于重性抑郁障碍的治疗,其主要作用机制与中枢神经系统(CNS)抑制5-羟色胺(5-HT)再摄取、增强5-HT活性相关。文中对沃替西汀的作用机制、药效学、药代动力学、药物相互作用、临床评价和安全性等进行综述。     

Vortioxetine: a review of efficacy,safety and tolerability with a focus on cognitive symptoms in major depressive disorder

Introduction: Vortioxetine is a pharmacodynamically novel antidepressant that exerts effects on various neurotransmitters including serotonin, noradrenaline, dopamine, glutamate, histamine and acetylcholine. Its efficacy in the symptomatic management of major depressive disorder (MDD) has been established in several short- and long-term trials. Vortioxetine has also demonstrated independent pro-cognitive effects in adults with MDD.

Areas covered: This report provides a concise review of the pharmacology, efficacy and safety of vortioxetine as they pertain to cognition.

Expert opinion: The significant impact of cognitive dysfunction in MDD has achieved increased consideration among researchers over the past decade. Vortioxetine is the first antidepressant agent to demonstrate meaningful clinical efficacy in the improvement of cognition in adults with MDD, independent of improvement in affective symptomatology. These results provide the impetus for further study into the potential pro-cognitive effects of vortioxetine in other conditions wherein cognitive dysfunction is prominent.     

Effect of Vortioxetine on Cognitive Impairment in Patients With Major Depressive Disorder: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BackgroundDementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.MethodsWe systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.ResultsSix RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.ConclusionsBoth the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.     

Randomized, 8‐week,double‐blind,placebo‐controlled trial of vortioxetine in Japanese adults with major depressive disorder,followed by a 52‐week open‐label extension trial

Aim

Safety and efficacy of vortioxetine (5–20 mg/day) in Japanese patients with major depressive disorder were evaluated in two phase 3 studies consisting of a short‐term, 8‐week, placebo‐controlled, double‐blind study followed by a long‐term, 52‐week, open‐label extension study.

Methods

The primary end‐point of the short‐term study was change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 8. The primary objective of the extension study was vortioxetine's long‐term safety; efficacy end‐points included change in MADRS total score, Clinical Global Impression Scale (CGI)–Severity (S) score from the long‐term study baseline, and CGI–Improvement (CGI‐I) score over 52 weeks.

Results

Of the 366 randomized patients, 338 completed the short‐term study, and 119 patients continued into the extension study. Primary (analysis of covariance) and secondary (mixed model for repeated measurements) analyses in the short‐term study showed numerically greater, but not statistically significant, decreases in change in MADRS total score from baseline between the vortioxetine and placebo groups at week 8. In the long‐term study, 86.6% of patients reported at least one treatment‐emergent adverse event, with the most common being nasopharyngitis (40.3%) and nausea (21%). MADRS total score and CGI‐I and CGI‐S scores improved with continued vortioxetine treatment from baseline of the open‐label study to week 52.

Conclusion

Vortioxetine failed to meet significance versus placebo in the primary efficacy analysis at week 8 in the short‐term study. The extension trial indicated continued improvement of depressive symptoms from baseline of this study throughout the 52‐week treatment period. Vortioxetine treatment was safe and well tolerated in both studies.