The use of agomelatine in OCD: effects on the motivational aspects and dysregulated circadian rhythms

Introduction: A considerable proportion of subjects with obsessive-compulsive disorder (OCD) have shown resistance or an incomplete response to the standard first-line treatment of serotonin reuptake inhibitors. In particular, patients often continue to show disrupted circadian rhythms with related sleep disturbances and comorbidity with bipolar spectrum disorders.

Areas covered: This paper discusses the possible role of agomelatine in the treatment of motivational aspects and dysregulated circadian rhythms of OCD. In particular, the article highlights the pharmacokinetics and pharmacodynamics of agomelatine. Additionally, the article highlights its clinical efficacy, safety and tolerability and provides perspectives on its future development as a potential therapy for the treatment of OCD.

Expert opinion: Agomelatine offers the effective resynchronization of circadian rhythm with an improvement in patients’ reward mechanism, incentive motivation and general OCD symptoms. Indeed, the authors believe that agomelatine could be a valid alternative drug in treatment-resistant OCD patients, particularly those suffering with bipolar spectrum comorbidity and related sleep disturbances.     

经颅磁刺激结合阿戈美拉丁治疗难治性抑郁症的临床研究

目的:探讨经颅磁刺激(TMS)结合阿戈美拉丁治疗难治性抑郁症的临床疗效.方法:选取2013年10月～2015年10月在本院门诊及住院诊治的137例难治性抑郁症患者,分为试验组:采用TMS结合阿戈美拉丁治疗67例;对照组:只进行TMS治疗70例.试验组应用高频(10 Hz以上)、低强度(运动阈值的95％)TMS治疗,持续时间15s,每次治疗刺激25次,每次间隔2 min,每日1次治疗,连续治疗5d为1个疗程,疗程之间间隔3d,共治疗2个月,同时给予阿戈美拉丁治疗,20 mg/d.对照组只用TMS治疗,疗程与试验组一致.采用SPSS 20.0进行统计学分析.结果:①试验组与对照组中,治疗后的汉密尔顿抑郁量表(HAMD)评分都低于治疗前(P＜0.05);治疗后,试验组的HAMD评分显著低于对照组(P＜0.01);②试验组与对照组中,治疗后的血浆去甲肾上腺素(NE)含量都高于治疗前(P＜0.05);治疗后,试验组的血浆NE含量显著高于对照组(P＜0.01);③试验组与对照组中,治疗后的平均巴氏指数(BI)都高于治疗前(P＜0.05);治疗后,试验组的平均BI显著高于对照组(P＜0.01);④试验组的治愈、显效和有效比例显著高于对照组(P＜0.01),试验组的无显效的比例显著低于对照组(P＜0.01).结论:TMS结合阿戈美拉丁治疗能明显改善抑郁症患者症状,治疗效果优于只应用TMS治疗的患者.     

塞来昔布对阿戈美拉汀抑制作用的体内外研究

目的：研究塞来昔布对阿戈美拉汀的体内外抑制作用及机制。方法：鼠肝微粒体体外实验得到塞来昔布对阿戈美拉汀的抑制机制,并在大鼠体内得到验证。因此,可通过人肝脏微粒体和重组CYP2C9.1蛋白体外实验预测塞来昔布在人体中对阿戈美拉汀的抑制作用和可能机制。结果：塞来昔布表现出明显抑制作用,该作用在CYP2C9.1中呈现浓度依赖性,而在鼠肝微粒体中表现为非竞争性抑制。结论：塞来昔布联合阿戈美拉汀进行抑郁治疗时可能会对后者产生非竞争抑制,这一作用能允许降低阿戈美拉汀的使用剂量,从而降低不良反应的发生,提高治疗的安全性。     

阿戈美拉汀治疗老年卒中后抑郁的临床疗效比较

目的探讨阿戈美拉汀对比度洛西汀治疗老年卒中后抑郁症的临床疗效和不良反应。方法将90例诊断为脑卒中后抑郁的老年患者随机分为2组,研究组使用阿戈美拉汀,对照组使用度洛西汀,治疗12周,采用汉密尔顿抑郁量表(HAMD)和神经功能缺损量表(CSS)、睡眠障碍量表(SDRS)、副反应量表(TESS)评定疗效、功能恢复和不良反应。结果研究组和对照组治疗老年脑卒中后抑郁的HAMD、CSS、SDRS评分无显著性差异,总有效率分别为73.3%和71.1%,差异无统计学意义(P>0.05);TESS显示研究组阿戈美拉汀不良反应少,2组差异有统计学意义(P<0.05)。结论阿戈美拉汀有利于老年脑卒中后抑郁患者改善抑郁症状,促进神经功能康复,提高生活能力,是一种安全有效、不良反应少的抗老年卒中后抑郁药。     

Melatonin and its analogs in insomnia and depression

Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.     

稳定的阿戈美拉汀晶型Ⅰ的制备方法

开发了一种稳定的阿戈美拉汀晶型I的制备方法。该方法采用在无水乙醇-正庚烷溶剂体系下添加PVP或在无水乙醇-水体系下添加HPMC的抗溶剂结晶法来实现。通过不同溶剂体系下高分子材料种类的筛选、不同浓度高分子材料的影响及溶剂体系中良溶剂和抗溶剂比例的影响的研究,确定了制备阿戈美拉汀晶型I的工艺。通过加速稳定性实验和长期稳定性实验对比表明,采用加高分子材料制备方法得到的阿戈美拉汀晶型I,具有较好的稳定性。     

阿戈美拉汀的药理机制及临床疗效

抑郁症是一种高患病率和高致残性疾病,现有的治疗药物主要是以单胺递质系统作为靶点。阿戈美拉汀是一种新型抗抑郁药,同时具有褪黑激素能激动和5-HT2C受体拮抗作用,动物实验和临床研究均显示出明确的抗抑郁效果,并且表现出起效时间早、药物耐受性好等特点,成为抗抑郁治疗的新选择。本综述总结了阿戈美拉汀的药理作用和临床疗效,希望有助于临床实践者更清楚认知该药,合理使用。     

人血浆中阿戈美拉汀浓度的测定及其药代动力学

建立测定人血浆中阿戈美拉汀浓度的LC-MS/MS方法,测定单剂量口服25 mg阿戈美拉汀片后其在中国健康受试者体内的血药浓度,利用Phoenix WinNonlin 6.3.0软件计算药代动力学参数。该方法中阿戈美拉汀浓度的线性范围为0.051 3~10.38 ng/mL(r=0.999 4),最低检测浓度为0.051 3 ng/mL。日内、日间精密度测定RSD均小于15%。单次口服给药后,阿戈美拉汀的c_max为(13.25±15.78)ng/mL,t_max为(0.68±0.41)h,AUC_last为(14.00±19.26)ng/mL·h,AUC_inf为(14.14±19.35)ng/mL·h,t_1/2为(0.78±0.44)h。本方法简便、准确、重现性好,可用于阿戈美拉汀血药浓度的测定及其人体药代动力学研究。