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Imipramine in alopecia areata. A double-blind, placebo-controlled study.

Alopecia areata (AA) is a dermatologic disease whose onset is significantly associated to life events. Its course may often be characterized by high levels of anxiety and depression. These observations suggested a rationale for using an antidepressant in AA. Thirteen patients were enrolled in a double-blind, placebo-controlled study of efficacy of imipramine in alopecia. After six months clinically significant hair regrowth occurred in 5 of the 7 patients on imipramine, whereas no response was observed in the placebo group. An improvement in psychic symptomatology was present in both groups. Our preliminary results indicate the potential efficacy of imipramine in patients with AA, not acting directly through a reduction of anxiety or depression.

Adult↗

Open trial and double-blind clinical trial of the antidepressant Ro 8-1998 in comparison with imipramine.

Based on the results of an open trial with Ro 8-1998 (chemic name: N,N-dimethyl-3-(1-methyl-5H-dibenzo(a,d)cycloheptene-5-ylidene)-propylamine N-oxide hydrochloride) in 11 endogenous depressed outpatients a double-blind trial with imipramine was proposed. Therapeutic efficacy and side effects of Ro 8-1998 and imipramine were compared in a double-blind trial with 30 patients who were newly hospitalized. Most of them suffered from endogenous depression. On days 0, 5, 10, 15 and 20 the patients were examined and the symptoms were documented with the AMP system, the Hamilton scale for depression, a behaviour rating and the "global depression rating Zurich". Ro 8-1998 caused a decrease of systolic blood pressure, an increase of heart frequency and urea. Twelve out of 15 patients showed a decrease of white blood cells. In four patients the number of white blood cells dropped below 4,000. Statistical analyses proved both substances to be potent antidepressants. The therapeutic efficacy of Ro 8-1998 was at least equal to that of imipramine. Further trials with bigger groups of patients are necessary to show whether the trend towards a better antidepressant efficacy of Ro 8-1998 can be reproduced.

Adult↗

Blood pressure and pulse changes in hyperactive children treated with imipramine and methylphenidate.

The authors found significant increases in systolic and diastolic blood pressure and pulse rate in hyperactive children treated with imipramine. Methylphenidate-treated children showed significant weight loss but no significant changes in blood pressure or pulse. The authors recommend caution in the use of imipramine and suggest the need for further study to determine short- and long-term effects of imipramine on blood pressure.

Adolescent↗

Imipramine and electrocardiographic abnormalities in hyperactive children.

The authors report seven cases of electrocardiographic abnormalities occurring in 7- to 10-year-old children receiving imipramine pharmacotherapy for behavior disorders. Three of the children evidenced a first-degree atrioventricular block. The abnormalities were less pronounced in the other four children. Imipramine plasma levels during steady state were not found to be directly related to the extent of the electrocardiographic changes within the obtained plasma values. The authors emphasize the necessity of careful clinical surveillance of children receiving imipramine pharmacotherapy.

Atrioventricular Node↗

The cardiac effects of therapeutic plasma concentrations of imipramine.

The authors studied the effects of imipramine hydrochloride at plasma concentrations associated with antidepressant activity in seven patients hospitalized for severe depressive illness. They found that the drug usually produced prolongation of intraventricular cardiac conduction. Although this was generally well tolerated, the authors suggest that patients with preexisting conduction system disease may be at increased risk when taking tricyclic antidepressants. They feel that the orthostatic hypotension seen in all seven patients represents a potentially serious problem with tricyclic antidepressants. They discuss the antiarrhythmic properties associated with imipramine and significant interactions between imipramine and drugs taken by patients with cardiovascular disease.

Adult↗

Imipramine response in deluded depressive patients.

The authors examined how delusions and other psychotic features influenced treatment outcome with imipramine in patients with primary depression. Global improvement scores indicated that delusions or other evidence of psychosis do not contraindicate imipramine treatment. This finding does not support a recent report suggesting that deluded depressive patients should not be treated with imipramine. Possible explanations of the discrepancy between these two studies are discussed.

Adult↗

Cardiovascular and antidepressant effects of imipramine in the treatment of secondary depression in patients with ischemic heart disease.

The authors report on 12 men with ischemic heart disease who developed secondary depression following myocardial infarction or coronary artery bypass-graft surgery and were treated with imipramine hydrochloride for 4 weeks. Imipramine had an antiarrhythmic effect, manifested by reduction in premature ventricular contractions during treatment. This drug did not produce clinically significant disturbances in cardiac conduction, but orthostatic hypotension led to early termination of the drug treatment in 1 subject. Imipramine treatment was associated with significant improvement in both observer-rated and patient-rated depression scales.

Adult↗

Bulimia treated with imipramine: a placebo-controlled, double-blind study.

Bulimia, the syndrome of compulsive binge eating, is a common and often severe disorder frequently resistant to known therapies. Recent evidence suggesting a link between bulimia and affective disorder prompted the authors to perform a double-blind study of imipramine versus placebo with 22 chronically bulimic women. Imipramine was associated with a significantly reduced frequency of binge eating and with improvement on several other measures of eating behavior. On 1- to 8-month follow-up, 18 of the 20 treated subjects (90%) had responded to imipramine or a subsequent antidepressant. This finding augments the growing evidence that bulimia may be related to affective disorder.

Adolescent↗

Tranylcypromine versus imipramine in anergic bipolar depression.

OBJECTIVE: This investigation compared the efficacy of the monoamine oxidase inhibitor (MAOI) tranylcypromine with that of the tricyclic imipramine in the treatment of anergic bipolar depressive illness. METHOD: A controlled, double-blind comparison was used to study 56 outpatients who met operationalized criteria for anergic bipolar depression. Patients with bipolar I and II depression were equally distributed between comparison groups. Outcome was measured by the patient-rated Beck Depression Inventory and the clinician-rated Hamilton Rating Scale for Depression, Raskin Mania and Depression Scales, Clinical Global Impression Scale, and the Pittsburgh Reversed Vegetative Symptom Scale. Twenty-eight patients were treated with tranylcypromine and 28 with imipramine. Seventy-three percent of bipolar depressive patients screened for the study met criteria for anergic depression, consistent with previous findings from studies in bipolar illness that stretch back over 100 years. RESULTS: Tranylcypromine produced statistically significant superior outcome in terms of lower attrition, greater symptomatic improvement, and higher global response without increased risk of treatment-emergent hypomania or mania. CONCLUSIONS: The authors propose that the apparently superior efficacy of tranylcypromine in bipolar depression is specifically linked to anergia and reversed neurovegetative symptoms. Bipolar I and bipolar II patients had comparable outcomes, but bipolar I patients had a significantly greater risk of treatment-emergent mood swings. Although the relatively poor showing of imipramine warrants close scrutiny, these findings provide further documentation of the utility of MAOIs in patients presenting with anergia, motor retardation, hyperphagia, and/or hypersomnia.

Adult↗

Seasonal rhythm of platelet [3H]imipramine binding in adolescents who attempted suicide.

OBJECTIVE: This study was designed to determine the seasonality of serotonin functions among adolescents who attempt suicide. METHOD: Platelet [3H]imipramine binding was assessed over a period of 18 months in 98 adolescents who attempted suicide and a comparison group of 23 never-suicidal youths with conduct disorder. RESULTS: [3H]Imipramine (Bmax) was uncorrelated with age, but showed considerable seasonal variability over time in those who had attempted suicide. CONCLUSIONS: [3H]Imipramine binding density in adolescents who attempted suicide exhibited significant seasonality, reaching a nadir in late winter/early spring.

Adolescent↗

Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes.

OBJECTIVE: The purpose of this study was to determine the effects of antidepressant pharmacotherapy on mood symptoms and psychosocial outcomes in dysthymia. METHOD: In a multicenter, double-blind, parallel-group trial, 416 patients with a diagnosis of early-onset primary dysthymia (DSM-III-R) of at least 5 years' duration without concurrent major depression were randomly assigned to 12 weeks of acute-phase therapy with sertraline, imipramine, or placebo. The psychosocial outcome measures used in the study were the Global Assessment of Functioning Scale, the Social Adjustment Scale, the Longitudinal Interval Follow-up Evaluation psychosocial ratings, and the Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Sertraline and imipramine were significantly better than placebo in improving psychosocial outcomes as measured by the first three instruments. The Quality of Life Enjoyment and Satisfaction Questionnaire scores demonstrated significant improvements from baseline, and both active treatments produced significantly greater improvements than placebo. Significantly fewer patients discontinued sertraline (6.0%) than discontinued imipramine (18.4%) because of adverse events. CONCLUSIONS: Pharmacotherapy is an effective treatment for dysthymia in terms of psychosocial functioning as well as depressive symptoms, even when the dysthymia is long-standing.

1-Naphthylamine↗

ECG changes in pediatric patients on tricyclic antidepressants, desipramine, and imipramine.

OBJECTIVE: To determine if there is an altered pattern of cardiac electrical activity in children treated with tricyclic antidepressants, desipramine, or imipramine, which may predispose these patients to sudden death. METHODS: All patients in a child psychiatry practice from 1989 to 1993 in Calgary, Alberta, treated with desipramine or imipramine with both pre- and post-treatment electrocardiograms (ECGs) were included in the study (n = 21; ages 8 to 17 years). Thirty-six blinded post-treatment ECGs were analysed for interval measurement and compared to the pretreatment ECGs. RESULTS: Drug dosages ranged from 25 mg to 125 mg per day and treatment duration ranged from 1 to 49 months. Seven of 21 patients were concurrently receiving an antipsychotic medication (pericyazine). The maximal increase in PR, and QRS, and QT interval changes were 40 msec and 70 msec, respectively, with most patients demonstrating no significant changes in the ECG intervals. The QT interval was corrected for heart rate (QTc). No significant arrhythmias or tachycardias were observed. ECG interval changes were not related to drug dosage, age, treatment duration or plasma levels. CONCLUSIONS: No consistent pattern of ECG interval changes including the QTc interval was observed in children on desipramine and imipramine.

Adolescent↗

Decreased imipramine binding in the brains of patients with depressive illness.

The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.

Aged↗

Imipramine-mediated interference with levodopa absorption from the gastrointestinal tract in man.

The effect of imipramine on the absorption of a single dose of levodopa was studied in male volunteers. By delaying gastric emptying and retarding delivery to intestinal absorptive sites, imipramine interfered with the absorption of levodopa. This action caused by the anticholinergic effect of imipramine. The retardation of transit of levodopa also caused the elaboration of therapeutically inactive metabolites of levodopa in the gastrointestinal tract. Antidepressants and levodopa are often given together, and this combination may interfere with the absorption and efficacy of levodopa in the treatment of Parkinson's disease.

Adult↗

Parkinson's disease: decreased density of 3H-imipramine and 3H-paroxetine binding sites in putamen.

The density of high-affinity 3H-imipramine and 3H-paroxetine binding sites (two serotonin-uptake blockers) was decreased in the putamen of parkinsonian patients. The correlation between serotonin levels and the number of 3H-imipramine and 3H-paroxetine binding sites suggests that they are located on serotoninergic nerve terminals and could be used to study serotoninergic innervation in the human brain. Since imipramine and paroxetine are powerful antidepressants, these results furthermore suggest that decreased serotoninergic transmission may be implicated in the pathophysiology of depression in Parkinson's disease.

Aged↗

Imipramine administered during an infantile period modifies sex difference in L-5-hydroxytryptophan-induced head shakes in rats.

Five mg/kg imipramine or desipramine was injected to infantile rats. L-5-Hydroxytryptophan-induced head shakes were assessed when rats were mature. The saline- and desipramine-treated adult male rats exhibited more sustained response to L-5-HTP than females. The time course of the head shake frequency in the imipramine-treated male and female rats showed a pattern between control males and females, resulting in no significant sex difference. The results suggest that infantile exposure to imipramine induces an alteration of the serotonergic neurons of the brain.

5-Hydroxytryptophan↗

Chronic effects of imipramine and lithium on 5-HT receptor subtypes in rat frontal cortex, hippocampus and choroid plexus: quantitative receptor autoradiographic analysis.

The effects of chronic treatment with imipramine or lithium on serotonin (5-HT) receptor subtypes were analyzed in the frontal cortex, hippocampus and choroid plexus of rat brain by quantitative receptor autoradiographic procedures, using radioligands [3H]-5-HT, [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT), [125I]-iodocyanopindolol ([125I]-CYP), [3H]-mesulergine and [125I]-7-amino-8-iodo-ketanserin ([125I]-ketanserin) or [3H]-spiperone. Chronic i.p. administration of imipramine (20 mg/kg/day for 21 days) decreased the densities of 5-HT1, 5-HT1A, 5-HT1C and 5-HT2 sites in the frontal cortex, hippocampus and choroid plexus. Lithium (2 mEq/kg/day for 21 days) also decreased the densities of 5-HT1, 5-HT1C and 5-HT2 sites in the frontal cortex, and the densities of those including 5-HT1A sites in the hippocampus and choroid plexus. Imipramine and lithium very markedly decreased the density of 5-HT1C sites in the choroid plexus. We propose that methods employing quantitative receptor autoradiographic analysis can be used to characterize and understand the local effects of these drugs on 5-HT receptor subtypes.

Animals↗

REM sleep deprivation potentiates the effects of imipramine and desipramine but not that of clomipramine in the forced swimming test.

Effects of REM sleep (REMs) deprivation on the basal swimming activity and the tricyclic anti-depressants-induced increase in swimming activity in the forced swimming test were investigated. Immediately after a 48-hr period of REMs deprivation, the basal swimming activity in REMs-deprived mice was significantly higher than those in group-housed and socially isolated animals used as the control groups. The REMs deprivation-induced increase in the swimming activity was not changed by adrenoceptor antagonists and it returned to the control levels 3 hr after the REMs deprivation treatment. Moreover, imipramine and desipramine but not clomipramine further increased the swimming activity enhanced by REMs deprivation at doses that did not affect the activity in the control groups. The enhancing effect of REMs deprivation on the sensitivity to imipramine and desipramine remained unchanged even at 3 hr after the REMs deprivation treatment, and it was blocked by the alpha 2-adrenoceptor antagonist yohimbine. These results suggest that the REMs deprivation-induced increase in basal swimming activity in the forced swimming test is not mediated by adrenoceptor mechanisms, whereas the enhancing effect of REMs deprivation on the sensitivity to imipramine and desipramine may be mediated by the functional changes in alpha 2-adrenoceptors in the brain.

Adrenergic alpha-Antagonists↗