文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效比较

目的 :比较文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效及安全性。方法 :文拉法辛组2 6例 ,用文拉法辛 50～ 2 0 0mg·d- 1,po ,bid～tid ;氯米帕明组 2 4例 ,用氯米帕明 50～ 2 0 0mg·d- 1,po ,bid～tid ;2组均以HAMD ,HAMA ,TESS评定观察 6wk。结果 :对抑郁症状的治疗 ,文拉法辛组与氯米帕明组显效率均为 84 % (P >0 .0 5) ;对伴随的焦虑症状的治疗 ,文拉法辛组显效率为 92 % ,氯米帕明组显效率为 63% (P <0 .0 5)。文拉法辛组常见不良反应为恶心 ( 2 7% )、口干 ( 19% )、便秘( 19% )、震颤 ( 12 % )、乏力 ( 8% )、头晕 ( 8% )等。结论 :文拉法辛治疗抑郁症伴焦虑症状的疗效肯定、耐受性良好 ,而且对焦虑症状的治疗效果优于氯米帕明     

糖皮质激素受体与重型精神病性抑郁症的治疗

1IntroductionPsychotic major depression ( PMD ), whichresponds poorly to tricyclic anti-depressants, is adistinct syndrome of depression. Hypercortisolemia(cortisone hypersecretion), a biological abnormalityexisting in many patients with PMD, has led to v…     

Double-blind trial of amineptine and clomipramine in the treatment of depression

Summary

A double-blind trial was carried out in 62 depressed patients to compare the clinical efficacy and acceptability of amineptine and clomipramine. Patients were allocated at random to one or other of two treatment groups and received daily doses of amineptine ranging from 100 to 300?mg (mean 180?mg) or of clomipramine ranging from 50 to 150?mg {mean 84?mg) over a period of 6 weeks. Global assessment of response to treatment and Hamilton Rating Scale scores, assessed before and after 1, 3 and 6 weeks of treatment, indicated that the two drugs appeared to be equally effective and no differences between them could be demonstrated in the analysis of the individual items or grouped items of the scale used. Measurements of ocular tone showed that there was significantly less risk of amineptine producing an increase in tone, and blood pressure and electrocardiographic investigations also underlined the greater cardiovascular tolerance of amineptine. Five (16%) of the 32 patients in the clomipramine group were withdrawn from the study because of adverse effects.     

盐酸氟西汀胶囊与氯丙咪嗪治疗儿童抑郁症对照研究

目的：了解盐酸氟西汀胶囊治疗儿童抑郁症的疗效和安全性。方法：对60例儿童抑郁症患者分别用盐酸氟西汀胶囊或氯丙咪嗪治疗6周，以汉密尔顿抑郁量表(HAMD)评定药物疗效，TESS评定不良反应。结果：盐酸氟西汀胶囊组与氯丙咪嗪组的有效率差异无显著性，但显效率更高，且不良反应显著低于氯丙咪嗪组。结论：盐酸氟西汀胶囊治疗儿童抑郁症疗效确切，不良反应少，依从性好，适用于儿童抑郁症患者。     

三种不同药物治疗抑郁症病人的成本-效果分析

目的 :评价 3种不同药物治疗抑郁症的经济效果。 方法 :对 115例抑郁症病人随机分组 ,分别用 3种不同的药物治疗 ,A组用氯米帕明 ,B组用氟西汀 ,C组用吗氯贝胺。运用药物经济学的最小成本分析及成本 效果分析方法比较。 结果 :3种方案的疗效无显著性差异 (P >0 .0 5 ) ,B方案不良反应发生率最低、成本 效果比最低。 结论 :药物经济学在优化治疗方案、指导合理用药、减轻病人经济负担方面具有重要意义。     

共患糖尿病的抑郁症患者皮质醇分泌节律的研究

目的探讨同时伴有糖尿病的抑郁症患者皮质醇分泌节律的特点,及其在抑郁症患者所发生的糖尿病病理机制中的意义。方法确诊糖尿病的抑郁症30例(观察组)测定8∶00、16∶00、24∶00血浆皮质醇浓度,同时测定空腹血糖、糖负荷后2 h血糖,并与正常糖代谢的抑郁症30例(对照组)进行对照。结果①观察组8∶00、16∶00、24∶00血浆皮质醇浓度分别为(607±269)nmol/L、(416±178)nmol/L、(376±264)nmol/L,显著高于对照组(485±178)nmol/L、(290±154)nmol/L、(173±117)nmol/L,差异有统计学意义(P均<0.05)。②观察组皮质醇分泌节律消失者为73.3%,显著高于对照组的46.7%(P<0.05)。③观察组8∶00、24∶00的血浆皮质醇浓度与空腹血糖值正相关(r值分别为0.338、0.418,P<0.05)。结论下丘脑-垂体-肾上腺轴功能紊乱可能是抑郁患者产生糖尿病的重要机制之一。     

Importance of oxidative polymorphism and levomepromazine treatment on the steady-state blood concentrations of clomipramine and its major metabolites

Summary The relationship between the debrisoquine oxidation status and the metabolism of clomipramine was studied in nine healthy volunteers (five rapid hydroxylators, three slow hydroxylators and one of intermediate status). The hydroxylation of clomipramine and demethylclomipramine were found to covary with that of debrisoquine, whereas demethylation of clomipramine seemed to be independent of the debrisoquine hydroxylation phenotype. The steady-state blood concentrations of clomipramine and its three main metabolites were measured in 122 depressed patients. Thirteen patients who concomitantly received a neuroleptic tended to have higher levels of demethylclomipramine and clomipramine, whereas the levels of the hydroxylated metabolites were hardly affected. Benzodiazepine co-administration did not modify the pharmacokinetics of clomipramine. The results suggest that benzodiazepines rather than levomepromazine should be used in depressed patients with anxiety and/or agitation in combination with the antidepressant treatment.     

Neuroendocrine effects of ipsapirone on the hypothalamic-pituitary adrenal axis: CRF,ACTH and cortisol in healthy volunteers

Summary The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks.The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5–30 mg per day were given.     

Novel approaches to the treatment of depression by modulating the hypothalamic - pituitary - adrenal axis

Many patients with major depression show evidence of over-activation of the hypothalamic - pituitary - adrenal axis (HPA), as evidenced by hypercortisolism and adrenal hyperplasia. Such over-activity is associated with increased corticotropin releasing factor (CRF) reactivity in the CSF and blunted release of ACTH in response to CRF infusion. Recent evidence suggests a switch from CRF to AVP regulation of the axis during depression, with depressed patients showing enhanced response to ddAVP infusion. The HPA provides multiple potential sites for antidepressant development. The use of glucocorticoid antagonists, cortisol synthesis inhibitors, CRF and AVP antagonists have been suggested. Copyright 2001 John Wiley & Sons, Ltd.     

氟西汀、氯丙咪嗪、文拉法新治疗抑郁症的成本-效果分析

目的：比较3种方案治疗抑郁症的经济效果和安全性。方法：运用药物经济学成本一效果分析对3种治疗方案进行分析评价。结果：氟西汀、氯丙咪嗪、文拉法新各组的治疗总成本，分别为28220元、25790．40元、55430．40元，有效率分别为85％、80％和87．5％，氯丙咪嗪组TESS得分显著及非常显著高于文拉法新及氟西汀组。结论：氟西汀组为最佳治疗方案。     

Cytokines: abnormalities in major depression and implications for pharmacological treatment

The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.     

A short-term open trial of clomipramine in the treatment of patients with panic attacks

Clomipramine was used to treat 14 patients with panic attacks. Diagnosis was made according to DSM-III criteria for agoraphobia with panic attacks or panic disorder uncomplicated. An open evaluation of the drug over an 8-week treatment period was conducted. A total of 10 patients completed the study. Clomipramine was effective in reducing the mean number of panic attacks, the greatest response being observed in the first 2 weeks of treatment. Findings on all outcome measures showed that clomipramine was also effective in alleviating depression secondary to panic attacks, non-specific aspects of anxiety and improving phobic avoidance. There was a suggestion that responders to treatment received lower doses of clomipramine than non-responders. Further studies are required to evaluate this issue and the role of clomipramine in the treatment of panic disorders.     

抑郁症致病机制及中药治疗抑郁症的机制研究

抑郁症严重危害人类身心健康,世界卫生组织预测：2020年抑郁症将成为非正常死亡和残疾的第二大原因。目前临床上大多使用三环类抗抑郁药（TCA）、四环类抗抑郁药、选择性5-HT再摄取抑制药等来治疗抑郁症,但长期应用这类药物易产生耐药性,不良反应明显,且这种通过单一成分阻断特定单一靶点的药物,对于涉及体内多个系统的生物学异常往往难以达到治疗效果。中药组方通过其所包含的多组分能同时调节多靶点、调节疾病网络的多个环节,在获得较高疗效的同时可降低化学药单靶点引起的毒副作用,且目前国内外对一些传统中药抗抑郁作用机制的研究报道也日渐增多,主要集中在神经递质水平释放、海马脑源性神经营养因子（BDNF）表达及细胞因子等方面。此外,最新的研究认为肠道菌群可能参与了从情感性疾病到神经系统疾病的发生发展。综述近年来中药抗抑郁神经保护作用的机制研究进展,以期为抑郁症发病机制探讨及抗抑郁药物研究提供借鉴和指导。     

Clomipramine/bentazepam combination in the treatment of major depressive disorders

Eighty-three patients were recruited in a multicentre study concerning the usefulness of benzodiazepines (BZ) in major depressive disorders, diagnosed according to the DSM-III-R criteria. After 1 week wash-out, patients were randomized to clomipramine (CLMP) or CLMP plus bentazepam (BTZ) treatments (47 and 36 patients respectively). It was necessary to add hypnotics, usually a BZ, in 11 patients in the CLMP group and in one patient in the CLMP + BTZ group. The clinical improvement was faster in the group treated with CLMP + BTZ and, at the end of 6 weeks of treatment, the mean score in Hamilton Anxiety Scale (HAS) was lower than the one found in the group treated with CLMP. There were no significant differences found in Hamilton Depression Scale (HDS) between the groups. The side-effects observed were those due to CLMP, and only drowsiness was more frequent in the CLMP+BTZ group. However, the CLMP+BTZ combination was equally or better tolerated by patients than by those treated with CLMP alone. Similar results were found in hospitalized as well as in outpatients. The tricyclic antidepressant (TCA)/BZ association showed better results than TCA alone, producing a symptomatic improvement extensive to the anxious components of depression.     

Neuroendocrine and anthropometric measures in major depression: the effect of antidepressant treatment

It has been suggested that weight change might be associated with certain neuroendocrine abnormalities often observed in patients suffering from a depressive illness. This preliminary study examined whether objective measures of weight change were associated with dexamethasone suppression test (DST) results or plasma levels of thyroid hormones, and whether they correlated with clinical improvement. Specific measures included plasma cortisol following dexamethasone, plasma free thyroxine (T4) and triiodothyronine (T3), as well as anthropometric measures (skinfolds, percentage body fat, body density). The majority of patients (75 per cent) showed some weight gain after treatment. A strong positive correlation was observed between weight gain and plasma tricyclic levels (P<0·005) but only a weak correlation was found between plasma tricyclic levels and therapeutic response (r=0·14). A gender difference was seen in the relationship between weight gain and therapeutic response, with weight gain being associated with less improvement in men and more improvement in women. Therefore, weight gain during treatment may not necessarily indicate clinical improvement for all patients. The only variable that reliably predicted treatment response was free T4. High levels of free T4 prior to treatment were highly correlated with better clinical status as indicated by HAMD scores (r=0·87, P<0·005). Following treatment with imipramine, plasma cortisol levels after dexamethasone administration were reduced in treatment responders but not in nonresponders. Overall, patients that showed the largest decreases in post-dexamethasone cortisol levels from before to after treatment also showed the largest decreases in HAMD total scores (r=0·37) and, especially, somatic anxiety scores (r=0·58, p<0·05). These effects were stronger in women than men. © 1997 John Wiley & Sons, Ltd.     

Response to clomipramine after short course of lithium in treatment-resistant depression: Does lithium have a ‘priming’ effect?

A patient with a treatment-resistant depression of 15 months duration is reported. Initially he showed no response to clomipramine 150 mg daily for 1 month. When lithium carbonate 600 mg daily was added for 4 days he developed signs of lithium intoxication: drowsiness, confusion, and dystonia. After lithium was withdrawn the patient improved dramatically. We hypothesize that lithium may potentiate the antidepressant effect of tricyclic antidepressants (TCA) even if it is administered as a short course of treatment.     

抑郁症患者血清皮质醇水平分析

研究抑郁症患者血清皮质醇水平的影响因素。方法59例抑郁症患者和17例健康人在入组第1天早晨和下午测血清皮质醇水平,抑郁症患者入组当天评定HAMD。结果抑郁症组的皮质醇水平显著高于健康对照组,从健康对照组、轻中度抑郁组到严重抑郁组疗前下午血清皮质醇水平逐步升高,HAMD总分及各因子分与疗前早晨和下午血清皮质醇水平及其差值无显著相关,首次发作抑郁症患者皮质醇水平较反复发作者倾向为高,但无显著差异。结论部分抑郁症患者的皮质醇水平升高,抑郁症患者血清皮质醇水平与抑郁严重程度正相关。     

米氮平与氯米帕明治疗心境恶劣障碍的对照研究

目的:观察米氮平治疗心境恶劣障碍的疗效和不良反应。方法:对70例心境恶劣病人随机分为2 组(米氮平组36例,氯米帕明组34例),分别给予米氮平及氯米帕明治疗,米氮平的最大剂量45 mg·d~(-1),氯米帕明的最大剂量200 mg·d~(-1),疗程6 wk,评定疗效及不良反应。结果:治疗1 wk末时,HAMD评定显示米氮平组优于氯米帕明组(P<0．01),2组间疗效比较经Ridit分析差异无显著意义(P>0．05),且不良反应少而轻。结论:米氮平是一种疗效好且安全的抗抑郁药物。     

文拉法辛缓释剂(24例)与氯米帕明(25例)治疗广泛性焦虑症的比较

目的 :比较文拉法辛缓释剂与氯米帕明治疗广泛性焦虑症的疗效和安全性。方法 :文拉法辛缓释剂组 (文拉法辛组 ) 2 4例 ,年龄为 (36±s1 2 )a,1 8～ 55a;氯米帕明组 2 5例 ,年龄为 (35± 1 2 )a,2 0～55a。文拉法辛用量 75～ 2 2 5mg·d-1 ,po,qd,氯米帕明用量 50～ 2 50mg·d-1 ,po,bid。共 6wk。疗效评定采用HAMA减分率。安全性评价应用TESS、体检和实验室检查。结果 :经过 6wk的治疗 ,文拉法辛组痊愈率为 2 7% ,有效率为 59%。氯米帕明组痊愈率为 33 % ,有效率为 62 % ,P >0 .0 5。另外 ,文拉法辛组的抗焦虑起效时间与氯米帕明组相近 ,不良反应较氯米帕明组少。结论 :文拉法辛缓释剂治疗广泛性焦虑症疗效与氯米帕明相似 ,可用于广泛性焦虑症的治疗