Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations

The aim of this paper is to describe two cases of clomipramine-induced delirium. One 61-year-old and one 67-year-old female depressive patients became delirious after beginning intravenous clomipramine injections in addition to their oral clomipramine administrations. Their plasma levels of both clomipramine and its metabolite, desmethylclomipramine, were acutely increased about twofold during delirium. The intravenous clomipramine administrations were discontinued. Their delirious state was gradually improved after stopping the intravenous clomipramine administrations. These findings suggest that acute increases of plasma levels of clomipramine and desmethylclomipramine after intravenous clomipramine injections might be related to the appearance of the delirious episodes.     

Effects of REM sleep deprivation on cholinergic receptor sensitivity and passive avoidance behavior in clomipramine model of depression

This study investigated the effects of REM (rapid eye movement) sleep deprivation (RSD) on the activity of central cholinergic receptors and passive avoidance retention in rats treated neonatally with clomipramine. Male rat pups treated with clomipramine (15 mg/kg, s.c.) twice daily from postnatal day 5 to 21 were subjected to RSD procedure at three months of age, for 4 days consecutively. In the post-RSD phase, RSD-control rats showed a significantly enhanced cholinomimetic-induced hypothermia and an improved retention in passive avoidance task. However, these measures were not significantly different in RSD-experimental group as compared to rats treated neonatally with saline. These results suggest that RSD reverses the sensitivity of central cholinergic receptors in rats given clomipramine neonatally, and this mechanism may be involved in mediating the antidepressant effects of RSD treatment in clomipramine model of depression.     

舍曲林与氯米帕明治疗强迫症对照观察

目的：探讨舍曲林与氯米帕明治疗强迫症的临床疗效和安全性。方法将62例强迫症患者随机分为两组,分别给予舍曲林、氯米帕明治疗,观察8周。采用耶鲁‐布朗强迫量表、副反应量表评定临床疗效及不良反应。结果治疗2周末起两组耶鲁‐布朗强迫量表评分均较治疗前显著降低（P＜0．01）,同期两组比较差异无显著性（P＞0．05）。两组总有效率比较差异无显著性（P＞0．05）,舍曲林组不良反应发生率显著低于氯米帕明组（P＜0．01）。结论舍曲林治疗强迫症疗效显著,与氯米帕明相当,但舍曲林安全性高。     

Successful use of intravenous clomipramine in depressive–catatonic state associated with corticosteroid treatment

We report two female patients who deteriorated to depressive–catatonic state after interepisode recovery from a hypomanic episode induced by corticosteroid treatment. Their symptoms developed during maintenance treatment with a low dose of prednisolone in Case 1 and after discontinuation of betamethasone in Case 2. Intravenous clomipramine successfully relieved their symptoms including reduction in contact and reactivity, immobility and mutism. These two patients showed no schizophrenic symptoms such as hallucinations and delusions. Corticosteroid-induced mood disorder can deteriorate into depressive stupor, severe depressive episode with catatonic features in DSM-IV. Clomipramine, a tricyclic antidepressant with relatively stronger serotonin reuptake inhibition, is one of the useful treatment options for corticosteroid-induced depression even in severe cases.     

RELATIVE BIOAVAILABILITY OF FOUR CLOMIPRAMINE HYDROCHLORIDE TABLET PRODUCTS

The relative bioavailability of clomipramine was determined in two single-blind, single-dose, randomized, crossover studies. In the first study, the relative bioavailability of the test product, 2×25 mg clomipramine hydrochloride tablets (Noristan Ltd.), with respect to the reference product, Anafranil^® 2×25 mg tablets (clomipramine HCl; Ciba—Geigy (Pty) Ltd.) was determined. In the second study, the relative bioavailability of the test product, 5×10 mg clomipramine hydrochloride tablets (Noristan Ltd.), with respect to the reference product, Anafranil^® 5×10 mg tablets (clomipramine HCl; Ciba—Geigy (Pty) Ltd.), was determined. The geometric mean values for the variable C_max were 31·.3 ng mL⁻¹ for the reference and 31·.6 ng mL⁻¹ for the test product in study 1. The geometric mean values for the variable AUC were 736 ng h mL⁻¹ and 753 ng h mL⁻¹ for the reference and test, respectively. In study 2, the geometric mean C_max values were 25·.8 ng mL⁻¹ and 23·.9 ng mL⁻¹ for the reference and test respectively; the geometric mean AUC values were 569 ng h mL⁻¹ and 547 ng h mL⁻¹. The 90% confidence intervals for the ‘test/reference’ mean ratios of the plasma clomipramine pharmacokinetic variables C_max and AUC_(0–∞) (as measures of the rate and extent of absorption of clomipramine, respectively) fall within the conventional bioequivalence range of 80–125% for both studies. The test products (clomipramine HCl) are therefore bioequivalent to the reference products (Anafranil^®) with respect to the rate and the extent of absorption of clomipramine in both 10 mg and 25 mg strengths.     

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。     

氯米帕明、帕罗西汀致咳嗽

1名72岁抑郁症女性患者在13年的时间内,先后服用了氯米帕明(最高剂量75mg/d)和帕罗西汀(最高剂量70mg/d)。患者在应用该2药后均出现咳嗽,咽痒,停用后咳嗽消失,再次服药咳嗽再现。     

Age-related adverse drug reactions to clomipramine

OBJECTIVE: The aim of this study was to determine whether age itself is a significant factor in predicting adverse drug reactions in depressed inpatients treated with clomipramine. METHOD: The study involved 150 hospitalized, depressed patients treated with 150 mg clomipramine per day. Changes in orthostatic blood pressure during treatment as well as the patients' complaint about side-effects was examined with regard to age. The sample was divided into younger (<56) and older (56-70) groups. RESULTS: No significant differences between younger and older subjects were found on any of the 44 side-effects recorded. However, older depressed patients suffer from more pronounced orthostatic hypotension than younger patients. CONCLUSION: Older depressed patients who have been treated with clomipramine suffer from more severe orthostatic hypotension than younger patients. However, with the right precautions it is safe to treat older patient up to the age of 70 years with a tricyclic antidepressant.     

Sympathomimetic effects of amezinium on the cardiovascular system and plasma catecholamines in man

Summary Thirty one in-patients suffering from depression were treated orally with clomipramine (Cl) at various dosage, for 28 days, after a “wash-out” period of three days. In 17 patients receiving 75 mg per day of Cl, steady state plasma levels of Cl were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMCl), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of Cl and DMCl continued to rise during the entire treatment period. At the steady state, a correlation was found between Cl dosage expressed as mg kg body weight and the plasma concentration of Cl and DMCl. Factors such as tobacco and alcohol consumption seem to modify the Cl/DMCl ratio. A comparison of clinical response with plasma levels of Cl, DMCl and Cl + DMCl showed a significant negative linear correlation.     

Antidepressants blunt the effects of inescapable stress on male mating behaviour and decrease corticotropin-releasing hormone mRNA expression in the hypothalamic paraventricular nucleus of the Syrian hamster (Mesocricetus auratus)

Stress decreases sexual activity. However, emerging research suggests that the psychological aspect of control prevents the detrimental effects of stress on male mating behaviour. The present study examined the effects of chronic escapable/inescapable stress on mating behaviour in the male Syrian hamster. Additionally, the ability of the antidepressant clomipramine to prevent the adverse effects of stress on mating behaviour was explored. In this paradigm, two groups received the same electric footshock stress, but differed in the psychological aspect of control. Cohorts were divided into two groups. One group received clomipramine via a sugar water solution while the other received plain sugar water. Mating behaviour was quantified before and after 12 consecutive days of stress. The morning following the final stress and behaviour session, trunk blood and brains were collected to assess: (i) plasma concentrations of testosterone and glucocorticoids and (ii) corticotropin-releasing hormone (CRH) mRNA expression within the paraventricular nucleus of the hypothalamus (PVN). In the drug-free groups, several aspects of mating behaviour were disrupted by inescapable but not escapable stress, including anogenital investigation before the first ejaculation and time of first ejaculation. Additionally, both escapable and inescapable stress caused a decrease in total hit rate compared to the no-stress control group. Unlike the sugar-water treated animals, hamsters in either stress condition receiving clomipramine showed no differences in anogenital investigation, time of first ejaculation, hit rate, or any other aspect of mating behaviour measured, compared to the clomipramine no-stress control males. The stress-induced inhibition of mating behaviour could not be explained by changes in baseline plasma concentrations of testosterone or total glucocorticoids; these values did not vary between any of the six treatment groups. It was found that clomipramine lowers CRH mRNA expression in the PVN by 74%, regardless of stressor conditions. The results of the present study have broad implications for understanding the relationships between stress, depression and reproduction, and for the treatment of people and animals suffering from the adverse effects of stress.