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At least 19 recordsLinked to original sources
PubMed1976

Determination of clomipramine and desmethyl-clomipramine in plasma or urine by the double-radioisotope derivative technique.

A double radioisotope derivative method was developed for the determination of clomipramine and desmethyl-clomipramine in plasma or urine. After addition of 14C-labeled clomipramine and desmethyl-clomipramine as internal standards and extractive isolation of both compounds, desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is separated from clomipramine by thin-layer chromatography and its radioactivity is measured. Clomipramine, extracted from the cilica gel, is reacted with trichloroethyl chloroformate. The urethane is saponified and decarboxylated. The resulting desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is purified by thin-layer chromatography and its radioactivity is measured. The sensitivity of the method is 15 mug/liter for clomipramine and 2 mug/liter for desmethyl-clomipramine. Its specificity was made sure by a cross-check with a gas chromatography-mass spectrometry technique.

Carbon Radioisotopes↗
PubMed1977

The demethylation of imipramine and clomipramine as apparent from their plasma kinetics.

The demetylation of imipramine and clomipramine was studied after administration by different routes of single doses of clomipramine hydrochloride and multiple doses of clomipramine as well as imipramine hydrochloride. Five healthy volunteers received 1 mg of clomipramine hydrochloride/kg body weight as single oral and intramuscular doses on different occasions for the purpose of studying the plasma levels of clomipramine and the desmethylclomipramine formed. Desmethylclomipramine was found in the plasma in four of the subjects after oral intake but only in one subject after intramuscular injection. The peak levels of clomipramine were considerably higher after intramuscular than after oral administration. The half-lives of clomipramine after oral administration ranged from 11.6-35.8 h (M = 20.8 +/- 4.0) and after intramuscular administration from 20.1--39.6 h (M = 24.7 +/- 3.7). Twenty subjects received either imipramine or clomipramine both orally and intramuscularly during a period of 3 weeks in a crossover design. The plasma levels of imipramine and clomipramine and their demethylated metabolites desipramine and desmethylclomipramine were determined during the treatment. The ratio between the plasma level of the parent drug and its demethylated metabolite was on average twice as high during intramuscular as during oral treatment.

Administration, Oral↗
PubMed1979

Clomipramine and amitriptyline in the treatment of severe pain.

Clomipramine is the most potent 5-HT reuptake blockade agent among the antidepressants. A comparison between the effect of clomipramine and a less powerful 5-HT reuptake blockade agent (amitriptyline) could test the hypothesis that brain 5-HT is a mediator of pain sensation. Groups of patients of either sex, with pain indication of trigeminal neuralgia, tension headache or postherpatic neuralgia, received doses of clomipramine or amitriptyline in a single blind clinical experiment. The results after three months of treatment showed that clomipramine: (1) was better than amitriptyline in treating trigeminal neuralgia; (2) tended to be better in the treatment of tension headache; and (3) amitriptyline is better in treating postherpatic neuralgia. Clomipramine was better tolerated. The results support the hypothesis that in certain pain situations, clomipramine exerts a beneficial effect, not only because of its effect on the depression and anxiety level of the patient, but also via its effects on the 5-HT brain system.

Adult↗
PubMedDate not supplied

Experimental evaluation of the possible neuroleptic activity of clomipramine.

Clomipramine, a new antidepressant, differs from imipramine by having chlorine in position 3 of the aromatic ring and in this respect resembles chlorpromazine. Clomipramine was therefore tested for neuroleptic activity. Clomipramine and imipramine were ineffective in inhibiting the traction response and pinna reflex in mice and in inducing catalepsy in rat. Compared to chlorpromazine they were less potent in blocking conditioned avoidance response and in decreasing spontaneous motor activity and exploratory behaviour. In contrast to chlorpromazine, clomipramine like imipramine was found to enhance methamphetamine-induced stereotyped behaviour. Thus clomipramine like imipramine possesses negligible neuroleptic activity.

Animals↗
PubMed1976

[The clomipramine-lithium combination: controlled trial].

A controlled study on a pragmatic type was performed on 30 patients of both sex, all having recurrent depressions. The efficacy of Clomipramine plus Lithium Carbonate was compared to that of Clomipramine plus placebo. The control consisted in a double-blind study with random sampling of patients. Results were recorded by an independant observer using a rating scale and were analysed statistically. In spite of the bias which was observed it seems possible to conclude. The association of Clomipramine plus Lithium Carbonate has no greater global antidepressive efficacy as compared with Clomipramine plus placebo which means that Lithium does not potentialize nor antagonize the anti depressant effect of Clomipramine. In respect of the number of patients : bipolar depressions (10 cases) unipolar (20 cases) it has not been possible to study the results in these 2 sub groups.

Adjustment Disorders↗
PubMed1979

Clomipramine-induced mania in unipolar depression.

Manic behavior during randomly assigned treatment with clomipramine (chlorimipramine) or amitriptyline hydrochloride developed in seven of 50 hospitalized unipolar depressed patients. Six of the 25 clomipramine-treated patients became manic. Only one patient in the amitriptyline-treated group developed manic behavior. The switch into mania occurred at the mean age of 63, much later than the reported age of risk for mania. Significant correlations were observed between the age at onset of mania, the number of days of clomipramine treatment, and the duration of the manic episode. We hypothesize that such a switch into mania in unipolar patients is triggered by the psychopharmacological effect of clomipramine through an alleged change in activity of the central dopamine and serotonin systems.

Adult↗
PubMed1979

Inhibition of platelet uptake of serotonin in plasma from patients treated with clomipramine and amitriptyline.

The inhibition of serotonin uptake by platelets has been measured in blood from 20 patients on amitriptyline (50--225 mg daily), 14 patients on clomipramine (25--200 mg daily), and in an untreated group of 21 depressed patients. A complete kinetic analysis was carried out in each patient. Using the increase in the kinetic parameter Km as a measure of uptake inhibition, there was high correlation between the daily dose and inhibition within each drug group, clomipramine being about 10 times more potent than amitriptyline. The inhibition did not vary with age, sex, duration of treatment (up to 3 years), or concomitant use of moderate doses of benzodiazepines, neuroleptics or lithium. In the amitriptyline group the inhibition was significantly smaller in smokers than in non-smokers. The kinetic parameter Vmax was essentially unchanged in the amitriptyline group, and was markedly reduced in the clomipramine group, but without any correlation with dose. The mixed competitive-noncompetitive effect of clomipramine confirms previous in vitro findings.

Adult↗
PubMed1977

Clomipramine (Anafranil) and musculo-skeletal pain in general practice: a pilot, open, non-comparative study of long-standing rheumatic pain.

Forty-six patients were admitted to an open general practice study of clomipramine (Anafranil) in the treatment of long-standing rheumatic pain; forty-one patients completed the trial. The duration of the trial was 56 days during which patients received daily doses of either 10 mg or 25 mg of clomipramine. Assessments were made at fortnightly intervals. Patients were assessed for pain using a visual analogue scale, analgesic requirement, joint pain, other pain and morning stiffness. At the completion of the study patients were asked whether the addition of clomipramine to their treatment was better, the same or worse than no additional treatment. Twenty-one patients (57%) felt that it was better, four felt that it was the same and twelve said that it was worse. The doctor also similarly recorded his preference at the end of the trial. In twenty-two cases (60%) the doctor felt it was better, in eight that there was no difference and in seven that it was worse. There was no difference between the 10 mg and the 25 mg regime. It is suggested that better control of rheumatic symptoms can be achieved in some patients by the addition of small daily doses of clomipramine to their standard anti-rheumatic therapy. The author expresses the view that further research in this field is merited.

Clomipramine↗
PubMed1977

A clinical trial of clomipramine and diazepam in the treatment of phobic and obsessional illness.

A double-blind comparative study of clomipramine and diazepam was carried out in patients suffering from phobic and obsessional disorders. Nineteen doctors submitted 58 patients. Seventeen patients withdrew from the trial, twelve because of side-effects. Forty-one patients completed the trial and of these 14 were on clomipramine and 27 were taking diazepam. Patients were assessed for phobias, obsessions, general psychiatric symptoms and side-effects and each was rated on a special symptom inventory at 0, 2, 4 and 6 weeks of treatment. A General Health Questionnaire and Burns Questionnaire was completed for each patient at the beginning and end of the study. General level of anxiety for diffuse phobic anxiety and situational anxiety for illness and death fears responded better to clomipramine than to diazepam. Global assessment showed significantly more progress on clomipramine than diazepam between weeks 4 and 6.

Adolescent↗
PubMed1977

A clinical trial of a 50 mg formulation of clomipramine (Anafranil) with steady-state plasma level measurements.

Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.

Adult↗
PubMed1977

Sexual side-effects of clomipramine (Anafranil).

An attempt was made to measure the effects of depressive illness and of clomipramine (Anafranil) therapy in doses of 30 mg and 75 mg daily on sexual appetite and performance. A special questionnaire was devised to gather information on sexual habits before illness, during illness and following treatment. It proved difficult to differentiate between the beneficial effects of recovery from depression and the possible adverse drug effects on sexual activity. Two patients dropped out of the study because of supposed sexual side-effects--a male with ejaculatory difficulties and a female with orgasmic impotence. Fifty-four patients completed the sexual questionnaire and a four-week course of clomipramine. There were nineteen males and thirty-five females. Sixty-eight per cent of males and 57% of females had their 'sex life' impaired by depressive illness. Coital rate was decreased and depression interfered with performance and satisfaction. Clomipramine therapy seemed to have advantageous and disadvantageous effects. The advantageous effects were probably associated with improvement in depressive illness. There was evidence that clomipramine had an adverse effect sexually in 26% of males and 14% of females. The effect was dose-related in females.

Adult↗
PubMed1977

Plasma level studies with clomipramine (anafranil)

Patients showing symptoms of depressive illness were treated in general practice with one of four clomipramine (Anafranil) dosage regimes (25 mg t.d.s., 75 mg o.n., 10 mg t.d.s. and 30 mg o.n.). Blood was sampled on admission to the study and at days 7, 14 and 28. Plasma analysis revealed that steady-state concentrations of clomipramine and its main metabolite desmethyclomipramine were reached at day 7 of treatment in each of the dosage groups. No apparent relationship between dosage and plasma level of clomipramine was found in this study since there was no significant difference between mean steady-state plasma levels in each of the four dosage regimes. In contrast, plasma concentrations of desmethylclomipramine appeared to be directly related to the dose of clomipramine administered. Intersubject variations in plasma levels of the parent compound within each dosage group ranged from three to fourteen-fold.

Adult↗
PubMed1977

Mass fragmentographic analysis of clomipramine and its mono-demethylated metabolite in human plasma.

A mass fragmentographic method for the quantification of clomipramine (CIM) and monodemethyl-clomipramine (DCIM) in human plasma was developed. The deuterium labelled analogues of the compounds were used as internal standards. The sensitivity of the method allows the determination of CIM and DCIM in plasma after oral doses with a standard deviation less than 7% at concentrations of 25 ng/ml. The method was applied to the analysis of drug concentrations in plasma of clomipramine treated healthy volunteers and depressed patients. After acute treatment the level of DCIM in plasma was low as compared to chronical treatment.

Adult↗
PubMed1978

Antagonism of the effects on thermoregulation of delta9-tetrahydrocannabinol by clomipramine in the rat.

1 The effect of pretreatment with clomipramine hydrochloride (15 mg/kg, i.p.) on the (--)-trans-delta9-tetrahydrocannabinol (delta9-THC)-induced changes in body temperature and brain amines of the rat was investigated. 2 A dose of 0.05 mg/kg of delta9-THC produced hyperthermia and a decrease in whole brain concentration of 5-hydroxyindoleacetic acid (5-HIAA). Doses of 2 and 5 mg/kg produced hypothermia and increases in brain 5-HIAA whereas 0.5 mg/kg did not affect either parameter. delta9-THC, at any of the doses, did not affect the whole brain concentrations of dopamine, noradrenaline or 5-hydroxytryptamine. 3 Clomipramine modified these responses of delta9-THC in that the dose-response curves appeared to be shifted to the right. 4 It is concluded that clomipramine acts as an antagonist to these actions of delta9-THC by interfering with entry of delta9-THC into tryptaminergic neurones.

Animals↗
PubMed1978

Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline.

The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group.

Adult↗
PubMed1979

Clinical response and tricyclic plasma levels during treatment with clomipramine.

Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly. These findings, together with the fact that significant clinical improvement was observed in only 55% of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.

Administration, Oral↗