米那普仑与度洛西汀治疗抑郁症的疗效和安全性评价

目的：比较米那普仑与度洛西汀治疗抑郁症的疗效和安全性评价,为临床治疗抑郁症提供可选择的药物。方法：采用随机对照、度洛西汀开放式6周对照研究。共收集抑郁症患者120例,米那普仑组60例,男37例,女23例,度洛西汀组60例,男33例,女27例,米那普仑初始剂量是50 mg·d^-1（po,bid）,度洛西汀的初始剂量是20 mg·d^-1（po,bid）。主要研究指标为基线到治疗6周后汉密尔顿抑郁量表17项（HAMD-17）总分的变化;次要研究指标汉密尔顿焦虑量表（HAMA）对治疗后患者一般情况进行评价,并应用不良反应量表（TESS）观察试验中不良事件的发生情况。结果：米那普仑组和度洛西汀组治疗6周末,米那普仑组HAMD-17总分下降了（14.56±3.25）,度洛西汀组下降了（14.62±3.19）;在各随访点,HAMD-17总分在2组间无明显差异（P>0.05）;米那普仑组和度洛西汀组的有效率分别为78.33%和76.67%,疗效上无明显差异（P>0.05）;2组HAMA评分无显著差异（P>0.05）;米那普仑组的不良事件发生率为13.33%（8/60）,度洛西汀组为21.67%（13/60）,2组相比有显著差异（P<0.05）。整个研究过程中无严重不良事件发生。结论：米那普仑与度洛西汀治疗抑郁症患者的疗效都有效且耐受性良好;米那普仑出现的相关症状更少。     

A Pooled Analysis of Two Randomized,Double‐Blind,Placebo‐Controlled Trials of Milnacipran Monotherapy in the Treatment of Fibromyalgia

Milnacipran has been shown to significantly improve the pain, global well‐being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n = 624), milnacipran 100 mg/day (n = 623), or milnacipran 200 mg/day (n = 837). Two different composite responder analyses were used to evaluate efficacy: a 2‐measure analysis, requiring ≥ 30% improvement from baseline visual analog scale 24‐hour recall pain scores and a Patient Global Impression of Change (PGIC) score of “very much improved” or “much improved”; and a 3‐measure analysis, requiring a ≥ 6‐point improvement from baseline in SF‐36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the milnacipran treatment groups than in the placebo group (2‐ and 3‐measure composite responder analyses: P ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of milnacipran treatment. The most common adverse events associated with milnacipran were nausea, headache, and constipation.     

新型抗抑郁药：米那普仑

米那普仑是一种新型抗抑郁药,对5-羟色胺(5-HT)及去甲肾上腺素(NE)的再摄取具有双重抑制作用,且强度相当。口服米那普仑具有较高的生物利用度和较低的血浆蛋白结合力,大部分以原型或葡萄糖酸苷的形式从尿中清除,与其他药物相互作用少。米那普仑的抗抑郁疗效与三环类相似,可能优于选择性5-羟色胺回收抑制剂(SSRIs),且耐受性良好。每日2次口服,50～150 mg·d~(-1)。该药为抑郁症的药物治疗提供了一种新的选择。     

Gender differences in the clinical effects of fluvoxamine and milnacipran in Japanese major depressive patients

Gender differences in the treatment response to fluvoxamine (selective serotonin re-uptake inhibitor) and milnacipran (serotonin/norepinephrine re-uptake inhibitor) were investigated in Japanese major depressive patients. A total of 125 Japanese patients was included in the present study. Sixty-six patients received fluvoxamine treatment. The daily dose was 50 mg/day for the first week and increased to 100 mg after 1 week, up to 200 mg after another week. Fifty-nine patients were given milnacipran. The daily dose was 50 mg/day for the first week, and up to 100 mg/day thereafter. Patients were divided into three groups: younger women (<44 years of age), older women (> or =44 years of age) and men. Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of the study. In comparison with other groups, younger women treated with fluvoxamine demonstrated a significant difference in the time course of MADRS score change. However, these gender/age-related differences of antidepressant response were not observed in the patients treated with milnacipran. The results suggest that fluvoxamine is more effective in younger female patients than older female patients and male patients, while milnacipran is generally effective irrespective of gender or age.     

Effects of milnacipran on binge eating - a pilot study

Selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors are effective in the treatment of bulimia nervosa. There have been relatively few studies of the efficacy of specific serotonin and norepinephrine reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were treated with milnacipran and 20 patients completed the 8-week study. Symptom severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE) self-rating scale before administration of milnacipran and after 1, 4, and 8 weeks treatment. The scores improved after 8 weeks, especially drive to, and regret for, binge eating. Milnacipran was more effective in patients without purging and in younger patients, while there was no difference in the efficacy of milnacipran among subtypes of eating disorders.     

Differential inhibitory effects of drugs acting at the noradrenaline and 5-hydroxytryptamine transporters in rat and human neocortical synaptosomes

Background and purpose:

Although the amino acid sequences of rat and human 5-hydroxytryptamine (5-HT) and noradrenaline (NA) transporters (i.e. SERT and NET) are highly homologous, species differences exist in the inhibitory effects of drugs acting at these transporters. Therefore, comparison of the potencies of drugs acting at SERT and NET in native human and rat neocortex may serve to more accurately predict their clinical profile.

Experimental approach:

Synaptosomes prepared from fresh human and rat neocortical tissues were used for [³H]-5-HT and [³H]-NA saturation and competition uptake experiments. The drugs tested included NA reuptake inhibitors (desipramine, atomoxetine and (S,S)-reboxetine), 5-HT reuptake blockers (citalopram, fluoxetine and fluvoxamine) and dual 5-HT/NA reuptake inhibitors (duloxetine and milnacipran).

Key results:

In saturation experiments on synaptosomal [³H]-5-HT and [³H]-NA uptake, the dissociation constants did not indicate species differences although a smaller density of both SERT and NET was observed in human tissues. In competition experiments with the various drugs, marked species differences in their potencies were observed, especially at SERT. The rank order of selectivity ratios (SERT/NET) in human neocortex was as follows: citalopram ≥ duloxetine = fluvoxamine ≥ fluoxetine > milnacipran > desipramine = atomoxetine > (S,S)-reboxetine. Significant species differences in these ratios were observed for duloxetine, atomoxetine and desipramine.

Conclusions and implications:

This study provides the first compilation of drug potency at native human neocortical SERT and NET. The significant species differences (viz., human vs. rat) in drug potency suggest that the general use of rodent data should be limited to predict clinical efficacy or profile.     

A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran

Concerning medical treatments for adult attention-deficit/hyperactivity disorder (AD/HD), case reports have gradually been accumulating on the efficacy of psychostimulants such as methylphenidate and amphetamine and selective noradrenaline reuptake inhibitors such as atomoxetine. However, patients intolerant to psychostimulants currently have a very limited range of treatments available to them. Here, we report a case of an adult AD/HD patient whose inattention and hyperactivity were remarkably alleviated by milnacipran, a serotonin noradrenaline reuptake inhibitor. Milnacipran has fewer side effects than comparable drugs, and we believe it could be developed into a good curative treatment for AD/HD in the future.     

Current progress in the pharmacological therapy of fibromyalgia

Fibromyalgia (FM) is a chronic musculoskeletal pain disorder often associated with fatigue, dyscognition, and sleep disturbances. Recent research advances highlight a critical role for aberrant central pain processing in FM, and, consistent with these data, the first three drugs approved by the FDA for FM over the past 2 years have a predominantly central mode of action. The first drug, pregabalin, may counteract central pain transmission by inhibiting presynaptic release of excitatory neurotransmitters, including substance P and glutamate. The serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran have been approved more recently and are believed to reduce pain by increasing serotonin and norepinephrine concentrations in descending inhibitory pain pathways. Agents with multiple other mechanisms of action are in development and promise an assortment of therapeutic options for this complex disorder in the near future.     

Differential effects of fluvoxamine, paroxetine and milnacipran for depression, especially with regard to age

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and dual serotonin and noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed classes of antidepressants, yet it is not known whether one is superior to the other. It seems that an investigation of the characteristics of patients being treated with SSRIs and SNRIs would be useful in determining which patients would be most likely to benefit from these antidepressant medications. AIMS: The purpose of this retrospective study was to compare the response to fluvoxamine, paroxetine and milnacipran treatment for depression with regard to patient age. METHODS: A retrospective cohort analysis was carried out among depression outpatients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2001. A total of 159 patients who met the criteria and who were receiving fluvoxamine, paroxetine and milnacipran were identified. To examine the influence of antidepressants with regard to patient age, the response rate of patients aged 50 years or older was compared with that of those aged 49 years or younger. RESULTS: In patients aged 49 years or younger, the clinical effect of fluvoxamine was greater than that of the other antidepressants. Conversely, in those aged 50 years or older, milnacipran had a tendency to be more effective than the others. CONCLUSIONS: The differential response of SSRIs and SNRIs with regard to age should help to guide clinicians in determining the selection of antidepressants for depression.