Mirtazapine orally disintegrating tablets in depressed nursing home residents 85 years of age and older

INTRODUCTION: Treatment studies of depression in the very oldest patients are infrequent. For these reasons, this study of mirtazapine orally disintegrating tablets was carried out in nursing home residents>or=85 years old with physician-diagnosed depression. The naturalistic conditions of the study allowed us to include patients with cognitive impairment, concomitant medications and comorbid illness. METHODS: This was a subgroup analysis of nursing home residents>or=85 years old who took part in a larger 12-week open-label trial. Patients were eligible if they had physician-diagnosed depression, and a Mini-Mental State Exam score>or=10. The physician or nurse coordinator obtained data from healthcare professionals in daily contact with the patient to complete the Clinical Global Impression (CGI) scale, a modified 16-item Hamilton Depression Scale (HAM-D), and the Cornell Scale for Depression in Dementia (CSDD). Treatment-emergent adverse events were recorded. RESULTS: Of the 50 patients enrolled at 23 sites, 72% completed the 12-week trial. The mean age of the participants was 89.3 years. The mean HAM-D score declined from 16.9 at baseline to 7.3 at endpoint (ITT, LOCF analysis) For the CSDD, the mean score declined from 15.1 to 7.1. The percentage of responders on the CGI-Improvement (CGI-I) scale increased at each assessment reaching 55% at endpoint. Only 10% of the patients discontinued treatment because of adverse events. There was a mean increase in weight of 1.32 lbs (0.6 kg) at day 84. CONCLUSION: Although lacking a placebo control, this naturalistic study suggests that mirtazapine orally disintegrating tablets were effective and well tolerated in this sample of depressed nursing home residents>or=85 years of age.     

米氮平维持治疗期抑郁症患者体重随访观察

目的探讨抑郁症患者在米氮平维持治疗期的体重增加问题。方法对单一服用米氮平治疗,出院时体重增加不低于3kg的45例患者进行为期24个月的门诊随访,患者每隔3月自来门诊1次,由原主治医师负责体格检查、精神检查、心理治疗及指导用药等。结果 45例患者中,有10例因病情反复退出研究,实际完成随访35例。与入院时比较,出院后3～6个月患者体重明显增加（P〈0.01或P〈0.05）,第9个月后逐渐恢复到入院时水平（P〉0.05）。结论使用米氮平治疗的抑郁症患者,在出院初期体重明显增加,后期可恢复到入院时的水平。米氮平维持治疗抑郁症对患者体重无明显影响。     

抗抑郁药米氮平的合成

以环氧苯乙烯和N-甲基乙醇胺为起始原料,经亲核开环、氯代和环合反应得到中间体1-甲基-3-苯基哌嗪。1-甲基-3-苯基哌嗪与2-氯-3-氰基吡啶亲核取代,再经水解、还原和环合等反应得到米氮平,总收率为22.6%,结构经1H-NMR和M S(质谱)确认,HPLC含量为99.79%。     

2-苯基哌嗪的合成

以苯乙酸为起始原料，经同锅溴代和酯化得到α-溴代苯乙酸乙酯，与乙二胺缩合生成3-苯基-2-哌嗪酮，再经氢化铝锂还原得到抗抑郁药米氮平中间体2-苯基哌嗪，总收率31．7％。     

米氮平治疗抑郁症的临床疗效及安全性

目的:比较米氮平与阿米替林治疗抑郁症的疗效及安全性。方法:63例抑郁症患者随机分为2组,米氮平组32例给米氮平30mg,po,qn;阿米替林组31例采取从小量逐渐加药的方式,d1～d2 25mg,d3～d4 50mg,d5～d6 75mg,d7起100mg,po,bid,2组疗程均为6周。结果:米氮平组6周末显效率84.4％,痊愈率65.6％;阿米 替林组6周末显效率83.9％,痊愈率61.3％。2组疗效差异无显著性(P>0.05)。药物不良反应发生率米氮平明显低于阿米替林。结论:米氮平治疗抑郁症有效,未发现严重不良反应。     

Mirtazapine in essential tremor: a double-blind, placebo-controlled pilot study.

We sought to determine whether mirtazapine is safe and well-tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double-blind, placebo-controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients.     

米氮平及曲唑酮辅助治疗镇静催眠药常规治疗无效失眠的对照研究

目的:了解米氮平对失眠的疗效和安全性。方法:对符合CCMD-3失眠症并使用镇静催眠药无效的30例门诊病人加用米氮平治疗,剂量10～30 mg·d~(-1),与曲唑酮对照,曲唑酮剂量25～200 mg·d~(-1),共观察8 wk。疗效在治疗后1,2,4,8 wk用阿森失眠量表评定;不良反应用TESS评定。结果:至wk 8,米氮平组减分值为(8±s 5)分,治愈14例(54％),曲唑酮组减分值为(6±3)分,治愈11例(41％),疗效与曲唑酮组无明显差异(P＞0．05),主要不良反应为头昏、瞌睡、乏力和体重增加等,不良反应除食欲减退较曲唑酮少外(P＜0．01),2组无显著差异:米氮平剂量(22±11)mg·d~(-1),曲唑酮剂量(62±38)mg·d~(-1)。米氮平组4例和曲唑酮组3例脱落。结论:米氮平可辅助治疗镇静催眠药无效的失眠病人,疗效与安全性与加用曲唑酮相似。     

国产米氮平治疗抑郁症25例

目的比较国产米氮平与帕罗西汀治疗抑郁症的疗效和副反应。方法将50例符合《中国精神障碍分类与诊断标准（第3版）》中诊断标准的抑郁症患者随机均分为两组，分别给予国产米氮平和帕罗西汀治疗6周，采用17项汉密尔顿抑郁量表（HAMD）和副反应量表（TESS）评定疗效与副反应。结果治疗6周后两组临床疗效比较无显著性差异，但治疗1周及2周后，米氮平组HAMD总分、焦虑躯体化和睡眠紊乱因子评分减少较帕罗西汀组明显（P〈0.05）。米氮平组副反应少且轻，与帕罗西汀组相比差异无显著性（P〉0．05）。结论国产米氮平治疗抑郁症安全有效且起效较快，具有抗焦虑及改善睡眠作用。     

米氮平的合成工艺改进

目的 研究抗抑郁药米氮平的合成工艺。方法 以2-氯-3-氰基吡啶和1-甲基-3-苯基哌嗪为起始原料，经烷基化、水解、还原、分子内傅克烷基化4步反应合成目标化合物米氮平。结果与结论 目标化合物的结构经元素分析、IR、¹H-NMR 、¹³C-NMR、MS谱数据确证。改进后的工艺，操作简单，生产成本低廉，总收率由文献的46%提高到60%，更适合工业化生产。