A comparison of paroxetine,clomipramine and placebo in the treatment of panic disorder

The aim of this 12-week, double-blind, parallel group, placebo-controlled study was to compare paroxetine with clomipramine in 367 patients with DSM-III-R defined panic disorder. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency, and was as effective as clomipramine. However, paroxetine appeared to have a more rapid onset of action than clomipramine in reducing the number of panic attacks to zero. There was an equivalent improvement with both paroxetine and clomipramine in the supportive efficacy variables which assessed associated aspects of therapeutic improvement. Significantly more adverse effects were reported in the clomipramine group compared with the paroxetine group, while there was no difference between the paroxetine and placebo groups.     

Long-term evaluation of paroxetine,clomipramine and placebo in panic disorder

Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies. This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder. Patients who satisfactorily completed a 12-week, double-blind, placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their randomized treatment for a further 36 weeks. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. In total, 176 patients were included in the intention-to-treat population. The number of full panic attacks decreased in all three groups during the 12-week study, and improvements continued with long-term therapy. Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks, and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks. There were no significant differences between paroxetine and clomipramine. The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group (19%) than in either the paroxetine group (7%) or the placebo group (9%). Paroxetine was significantly more effective than placebo and as effective as (but better tolerated than) clomipramine in the long-term treatment of panic disorder. Not only was efficacy maintained, but continued improvement was also seen, indicating the importance of long-term treatment in patients with panic disorder.     

西酞普兰与氯米帕明治疗强迫症对照研究

目的：比较西酞普兰与氯米帕明治疗强迫症的疗效和不良反应。方法：以西酞普兰和氯米帕明治疗强迫症各30例,疗程8周。应用Yale—Brown强迫症量表（Y—BOCS）、汉密尔顿抑郁量表（HAUD）及汉密尔顿焦虑量表（HAMA）评定疗效。结果：西酞普兰组与氯米帕明组治疗后Y-BOCS、HAMD、HAMA分值均显著下降,两组间差异无显著性。西酞普兰组不良反应明显少于氯米帕明组。结论：西酞普兰治疗强迫症疗效与氯米帕明相仿,不良反应较轻,值得推广。     

帕罗西汀与氯米帕明治疗难治性强迫症对照研究

目的：观察帕罗西汀和氯米帕明对难治性强迫症的疗效和不良反应。方法：对难治性强迫症患者60例,随机分为两组,分别用帕罗西汀和氯米帕明治疗8周。采用强迫症量表（Y-BOCS）和副反应量表（TESS）评价疗效及不良反应。结果：两药的总体疗效相仿。帕罗西汀对强迫行为疗效较好,不良反应小,尤其是心血管系统及抗胆碱能不良反应少。结论：帕罗西汀尤适用于以强迫行为为主的难治性强迫症患者。     

Comparative effects of low and high doses of clomipramine and placebo in panic disorder: a double-blind controlled study. French University Antidepressant Group

This study was designed to explore the dose-response relationship for clomipramine in patients with panic disorder, with or without agoraphobia. After 1 week of single-blind placebo pretreatment, 180 such patients were assigned to a multicentre placebo-controlled comparison of the effects of high and low doses of clomipramine, and were followed up for 8 weeks. In alleviating anxiety and panic disorder, both clomipramine doses were more efficacious than placebo for panic disorder and, to a lesser degree, for phobia. The lower dose was better tolerated and at least as effective as the higher dose, sometimes more so. These results indicate the clinically important possibility that low-dose clomipramine is effective and well tolerated.     

Panic attacks in the differential diagnosis and treatment of resistant epilepsy

The authors present four patients displaying panic disorder and a history of epileptic seizures to illustrate difficulties regarding differential diagnosis between epileptic seizures and panic attacks. The cases describe the aversive properties of epileptic seizures, the role of visual seizure-triggering stimuli as phobic cues, and the effectiveness and safety of clomipramine treatment of panic attacks as an adjunct to concurrent antiepileptic medication.     

Differential drug response of panic and agoraphobic avoidance in a case of panic disorder

A case is presented of a patient with severe panic disorder and agoraphobia in whom initial treatment with clomipramine resulted in complete elimination of panic attacks, with no improvement in agoraphobic avoidance. The addition of phenelzine to the pre-existing clomipramine treatment resulted in rapid and complete disappearance of the agoraphobic avoidance. The possible implications of this case for our understanding of the neurobiological relationship between panic attacks and agoraphobia are discussed.     

舍曲林与氯米帕明对强迫症患者生活质量的影响

目的:探讨舍曲林与氯米帕明对强迫症患者生活质量的影响.方法:应用舍曲林与氯米帕明分别治疗强迫症各30例,采用Yale-Brown强迫量表、生活质量综合评定问卷(GQOLI-74)分别于治疗前和治疗8周末进行疗效和生活质量评估.结果:舍曲林和氯米帕明对强迫症疗效相当,但舍曲林不良反应少,对患者生活质量的提高优于氯米帕明(P＜0.05).结论:舍曲林比氯米帕明能更好地改善强迫症患者的生活质量.     

Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression

Milnacipran is a new antidepressive drug, a combined noradrenaline/serotonin (NA/5-HT) reuptake inhibitor, which has been suggested to be as effective as and better tolerated than tricyclic antidepressants. Since long-term studies are lacking, we compared the efficacy, safety and tolerability of milnacipran and clomipramine in a double-blind, randomized, parallel-group study setting during 26 weeks of treatment in patients with major depression. A total of 107 patients were treated with either milnacipran (n=52) or clomipramine (n=55). Due to active treatment of duration less than 12 days in four patients and protocol deviation in one patient, in total 47 milnacipran-treated patients were eligible for efficacy analysis. Nine patients in the clomipramine group continued on active treatment for less than 12 days. Thus 46 clomipramine-treated patients were finally included in the efficacy analysis. After 1 week of dose escalation, there was a fixed dosage regimen of either milnacipran (200 mg daily) or clomipramine (150 mg daily) during weeks 2 to 10, followed by flexible dosing of milnacipran (100,150 or 200 mg daily) or clomipramine (75, 100 or 150 mg daily) during weeks 11 to 26. A total of 53 patients (49%) completed the 26-week study period; 21% (11/52) of the patients in the milnacipran group and 38% (21/55) of the patients in the clomipramine group discontinued their medication prematurely due to adverse events, whereas 19% (10/52) of those on milnacipran and 7% (4/55) of those on clomipramine treatment withdrew due to either lack of efficacy or clinical deterioration. The mean change (±SD) in the Hamilton Depression Rating Scale (HAMD) score between the baseline and the last rating ranged from 23.7±3.1 to 12.0±9.5 in the milnacipran-treated patients and from 23.1±3.5 to 8.0±8.5 in the clomipramine-treated patients, revealing a significant difference in favour of clomipramine. In total 58% of the milnacipran-treated patients vs. 72% of the clomipramine-treated patients showed a ≥50% reduction in their baseline HAMD scores and 45% vs. 63% had an HAMD score of ≤7 at the last rating, respectively. Moreover, the time to the onset of the antidepressant action (defined as ≥50% reduction of the baseline HAMD score) showed a significant difference in favour of clomipramine. In addition, clomipramine was significantly more efficacious in patients with a baseline HAMD score of ≥24 as evidenced by the analysis of the HAMD score at week 6 and at the last rating. The Montgomery Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale did not show significant differences between the treatment groups. The safety analysis did not reveal any differences of clinical significance in cardiovascular variables between the study drugs. Dry mouth was significantly less frequently reported by the milnacipran-treated patients during the early and later phases (weeks 6 to 26) of the study, while insomnia was more common in the milnacipran group during weeks 1 to 6. In conclusion, milnacipran appeared to be less effective than clomipramine in the long-term treatment of depression. The side-effects of the drugs differed to a certain extent, and milnacipran tended to be somewhat better tolerated than clomipramine.     

A case report of refractory obsessive-compulsive disorder improved by risperidone augmentation of clomipramine treatment

A male patient aged 43 years, suffering from symptoms of obsessive-compulsive disorder (OCD), such as washing hands and feet frequently and checking documents compulsively, had received intensive pharmacotherapeutic and behavior therapy. Although the administration of anxiolytic drugs and/or clomipramine did not show curative effects, a combination of clomipramine and risperidone showed much greater effect in improving these symptoms.     

Is there a relationship between response to total sleep deprivation and efficacy of clomipramine treatment in depressed patients?

Total sleep deprivation (TSD) and tricyclic medication are successful treatment modalities for patients with a major depressive disorder. Recent studies have suggested a positive relationship between TSD response and succeeding tricyclic treatment, even on a very specific level, thus supporting the assumption of two distinct biochemical subtypes of depression. The present study tested this hypothesis by treating 10 inpatients with a major depressive disorder first with TSD and succeedingly with clomipramine. Contrary to expectation, a negative relationship between clinical response to the two treatment modalities was found.     

文拉法辛和氯米帕明治疗老年抑郁症对照研究

目的:比较文拉法辛和氯米帕明对老年抑郁症的疗效和不良反应。方法:70例老年抑郁症患者随机分为两组,分别用文拉法辛和氯米帕明治疗,疗程6周。采用汉密尔顿抑郁量表(HAMD)、临床疗效总评量表(CGI)和副反应量表(TESS)评定疗效和不良反应。结果:文拉法辛和氯米帕明治疗老年抑郁症疗效相似,但文拉法辛比氯米帕明见效快,不良反应轻,疗效指数好于氯米帕明(P<0.05)。结论:文拉法辛是一种安全有效、见效快、不良反应轻的治疗老年抑郁症的药物。     

Enhanced binding of [3H] (-) adrenaline to platelets of depressed patients with melancholia: effect of long-term clomipramine treatment

The specific binding of the full agonist [3H] (-) adrenaline to platelet membranes was measured in 14 drug-free depressed patients with melancholia. There was an increased number of binding sites (Bmax) with the same apparent affinity (KD) for the radioligand, indicating that platelet alpha 2-adrenoceptor density in the high affinity state was increased in depressed patients. Long-term administration of clomipramine was associated with decreases in platelet alpha 2-adrenoceptor densities which correlated with the duration of treatment. The results support the hypothesis that in endogenous depression there is a dysfunction of the alpha 2-adrenoceptor and that antidepressant treatment might involve a time-dependent desensitization process of this receptor.     

米氮平和氯米帕明维持治疗抑郁症对照观察

目的:比较抑郁症患者用米氮平和氯米帕明维持治疗的疗效.方法:将60例门诊抑郁症患者随机分为服用米氮平组和氯米帕明组,均治疗54周,用汉密尔顿抑郁量表(HAMD)临床疗效总评量表(CGI)和副反应量表(TESS)在治疗前及治疗12、54周末比较两组的疗效和依从性.结果:治疗12周两组均有非常显著的疗效,两组间比较差异无显著性;治疗54周以米氮平组显著较好.米氮平组不良反应发生率远低于氯米帕明组.结论:抑郁症患者对米氮平依从性高主要是因疗效好,不良反应轻.     

Comparison of the serum levels in primary non-agitated depressed out-patients treated with imipramine in combination with placebo, diazepam or dixyrazine

Sixty-three non-agitated depressed out-patients were selected according to the Feighner-Robins-Guze criteria for primary depressions for a double-blind, between-patient randomized study for an 8 week duration. All the patients were treated with imipramine following a fixed dose schedule for the first 2 weeks and thereafter according to clinical response (100-200 mg/day). This treatment was combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day). The serum concentration of imipramine both at 2 weeks and later was significantly higher (P less than 0.05) in the group treated with dixyrazine than in the other two groups. In the group treated with diazepam, the serum levels of imipramine and desipramine were significantly lower than in the placebo group. The serum concentrations of diazepam, desmethyldiazepam and dixyrazine were almost unchanged during the study. No significant correlation was found between the dosage and the serum concentration of imipramine or desipramine. The change in mean CPRS-score correlated neither with the imipramine nor with the desipramine serum levels, it did correlate but negatively with the degree of side effects. The degree of side effects correlated positively with the serum concentration of desipramine.     

氯米帕明联合认知疗法治疗躯体化障碍的对照研究

目的 评价氯米帕明联合认知心理治疗躯体化障碍患者的临床疗效.方法 对符合CCMD-3诊断标准的40例躯体化障碍的患者随机分为治疗组和对照组各20例.2组病例均给予氯米帕明片治疗,疗程8周,治疗组同时联合心理认知治疗.采用汉密顿抑郁量表(HAMD)评定疗效.结果 经过8周治疗后,患者各系统症状发生率较治疗前均明显下降,汉密顿抑郁量表评分均较治疗前显著下降(P＜0.01).结论 氯米帕明联合认知治疗躯体化障碍优于单用氯米帕明.     

心理行为干预联合帕罗西汀治疗惊恐障碍患者的临床疗效

目的:观察心理行为干预联合帕罗西汀对惊恐障碍的治疗效果。方法:60例住院惊恐障碍患者随机分为,研究组和对照组各30例。研究组给予心理行为干预联合帕罗西汀治疗,对照组单用帕罗西汀治疗。观察12周。采用汉密尔顿焦虑量表(HAMA)、临床疗效总评量表-病情严重程度(CGI-SI)在治疗前及治疗2、4、8和12周评定疗效;以治疗中出现的症状量表(TESS)评定不良反应。结果:两组治疗后HAMA及CGI-SI评分较治疗前均显著降低(P<0.05),两组比较,研究组下降更为明显(P<0.05)。结论:心理行为干预联合帕罗西汀治疗惊恐障碍效果优于单用帕罗西汀治疗。     

氯丙咪嗪合并利培酮治疗强迫症的对照研究

目的探讨利培酮对于氯丙咪嗪治疗强迫症的增效作用。方法将70例强迫症随机分为2组,氯丙咪嗪同时合并利培酮和单独使用氯丙咪嗪治疗,治疗8周。采用强迫症量表(Y-BOCS)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评定疗效。结果合并利培酮组有31例完成试验,氯丙咪嗪组有32例完成试验。治疗8周后,两组Y-BOCS平均总分有明显下降,合并利培酮组优于氯丙咪嗪组,两组无显著性差异(P<0.05);HAMA、HAMD的评分均显著下降,两组无显著性差异(P>0.05)。结论合并利培酮对于氯丙咪嗪治疗强迫症有增效作用。     

Clinical efficacy of tandospirone augmentation in patients with major depressive disorder: a randomized controlled trial

The purpose of the present paper was to investigate the efficacy of augmentation of clomipramine (CMI) by tandospirone in 36 untreated outpatients with major depressive disorder. Twelve patients were treated with CMI and tandospirone (T group), 12 with CMI and diazepam (D group) and 12 with CMI alone (C group) for 6 weeks. No statistically significant differences in the percentage improvement of the Hamilton Depression Rating Scale (17 items; HDRS-17) and the Hamilton Anxiety Rating Scale (14 items; HARS-14) scores were shown among the three treatment groups. However, at 2 weeks, the percentage improvement of HDRS-17 score in the T group tended to be higher than that in the D and C groups, although there was no statistically significant difference among the three treatment groups. No change in plasma prolactin level or adverse events was induced by the addition of tandospirone. These results suggest that 6 weeks of treatment with tandospirone or diazepam was not effective for augmentation of CMI in major depressive disorder patients. However, augmentation of antidepressants by tandospirone administration for a few weeks might induce early expression of antidepressive effects.     

101例惊恐发作患者诊断归属及发作场所调查

目的:分析101例惊恐发作患者诊断归属及发作场所变化。方法:对101例惊恐发作患者以美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)轴Ⅰ障碍用定式临床检查-临床版(SCID-CV)进行诊断;采用自制问卷调查发作情况。结果:符合DSM-Ⅳ惊恐障碍90例(89.1%),广泛性焦虑障碍6例(5.9%),抑郁障碍3例(2.9%),强迫障碍及精神分裂症各1例。90例惊恐障碍患者中,首次发作场所为家中50例,公共场所31例,途中9例;76.6%患者常在初次发生发作的场所发作,23.4%发作场所没有倾向性,仅1例发作场所固定。11例非惊恐障碍患者首发场所为家中3例,公共场所8例;此后发作场所均不固定。结论:约90%惊恐发作患者诊断为惊恐障碍,首次多发作于家中,并且倾向于在初次发作的场所发作;非惊恐障碍患者发作场所不固定。