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PubMedDate not supplied

Cardiotoxicity in imipramine intoxication: report of one case.

Imipramine is the most commonly prescribed tricyclic antidepressant of acute life threatening self-poisoning. We report a 15-month-old boy of accidental poisoning with imipramine, who developed generalized tonic-clonic convulsions and drug-related cardiac conduction abnormalities with PR prolongation, QRS widening, and QTc lengthening. The patient's imipramine level was 1389 ng/ml. The rapid resolution of intraventricular conduction delay and normalization of the QRS-T complexes after gastric lavage, installation of activated charcoal and alkalinization of the blood strongly implicates imipramine intoxication in the etiology of the cardiotoxicity. The patient made a full recovery without neurological sequelae.

Antidepressive Agents, Tricyclic↗
PubMed2002

Bright light therapy and/or imipramine for inpatients with recurrent non-seasonal depression.

INTRODUCTION: The aim of a double-blind study was to assess the efficacy of bright light therapy and/or imipramine in the treatment of inpatients suffering with recurrent non-seasonal major depressive disorder. METHOD: 34 in-patients with DSM-III-R diagnosis of major depressive disorder, recurrent type, were randomly allocated into 3 treatment groups. After 4-day washout period with baseline assessment they underwent 3 weeks of different types of treatment: a) Group A: bright light therapy (5000 lux from 6-8 a.m.) and imipramine 150 mg/day. b) Group B: bright light therapy (5000 lux from 6-8 a.m.) and imipramine-like placebo. c) Group C: dim red light (500 lux from 6-8 a.m.) and imipramine 150 mg/day. Outcome measures included weekly Hamilton Psychiatric Rating Scale for Depression, Clinical Global Impression Scale, Montgomery and Asberg Psychiatric Rating Scale for Depression and Beck Depression Inventory. RESULTS: Patients of all three groups improved significantly. The improvement of the patients of group B treated with bright light therapy plus placebo was superior to the other two groups, but not significantly. CONCLUSION: Bright light therapy can be effective in the treatment of non-seasonal major depressive disorder.

Adult↗
PubMed1992

Paroxetine in major depression: a double-blind trial with imipramine and placebo.

Paroxetine is a selective serotonin reuptake inhibitor which is being developed as an antidepressant. Previous studies suggest it is effective in the treatment of depression and has a low incidence of side effects. The authors report on a 6-week, randomized, prospective trial of paroxetine, imipramine, and placebo in 120 outpatients with major depression. The results showed that paroxetine was significantly superior to placebo in relieving depression. There were no significant differences in antidepressant efficacy between paroxetine and imipramine. However, paroxetine was also significantly superior to placebo on several measures of anxiety. Imipramine either was not superior on these measures or took longer to show a significant difference. Paroxetine lacked the typical anticholinergic side effects that accompanied imipramine therapy. The results show that paroxetine is an effective antidepressant that may have value especially when depression is accompanied by significant anxiety.

Adult↗
PubMed1992

The comparative efficacy of trazodone and imipramine in the treatment of depression.

OBJECTIVE: To review published clinical trials comparing the efficacy of trazodone with that of tricyclic antidepressant medication. DATA SOURCES: MEDLINE was searched for relevant articles published from 1983 to 1991. The bibliography of a review article was searched for further references. STUDY SELECTION: In all, 25 clinical trials were found. Six of these met the methodologic assessment criteria (adapted from the McMaster guidelines for the evaluation of clinical trials), which included the stipulation of a score of 18 or more on the Hamilton depression rating scale and a 50% reduction in that score as an outcome measure. DATA EXTRACTION: All six studies compared trazodone with imipramine. Data describing response to the treatments were extracted, and post-hoc power estimates were calculated. The analysis also involved statistical tests of a modified null hypothesis, the generation of confidence intervals (CIs) and a meta-analysis. DATA SYNTHESIS: All the studies found no significant difference in the efficacy of trazodone and imipramine. However, the statistical power of most of them was less than 50% and often less than 10%; thus there was a low probability that differences would be detected. The results of statistical tests of the modified null hypothesis, inspection of the CIs and the results of the meta-analysis all suggested that trazodone, and imipramine are equally efficacious. CONCLUSION: The application of various techniques for the analysis of equivalence data suggests that trazodone and imipramine are of approximately equivalent efficacy. The data are compatible with small differences in efficacy, but the differences are of a magnitude such that they are unlikely to be of clinical significance.

Clinical Trials as Topic↗
PubMed1992

A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly.

The efficacy and safety of alprazolam as compared to imipramine or a placebo added to weekly interpersonal psychotherapy was compared in a 6-week double-blind randomized clinical trial of 35 ambulatory elderly patients with major depression. The average maximum dosage of alprazolam was 2.2 mg and the average maximum dosage of imipramine was 97.5 mg. The findings showed a rapid onset of action of alprazolam within 1 week on symptoms of depression and anxiety. The effects for imipramine were seen later in the study. There were no serious side effects that interfered with treatment. The anticholinergic effects of imipramine were the ones that most commonly interfered with treatment. Alprazolam produced the greatest number of symptoms with discontinuation, most of which were alleviated within a week. We conclude that alprazolam may be useful as an antidepressant for the elderly. More clinical trials are needed to test its efficacy in the depressed elderly with concomitant medical problems, using plasma levels. A double-blind discontinuation study of alprazolam is needed to determine the degree of symptom return.

Aged↗
PubMedDate not supplied

Strain differences in changes in some parameters of cerebral cortical adrenergic system following chronic imipramine administration to rats.

The characteristics of [3H]prazosin binding sites in the membranes from cerebral cortex, the basal level of formation of cyclic AMP in cortical slices, and the responsiveness of the cyclic AMP generating system to noradrenaline and isoproterenol in this preparation were measured in Long-Evans, Wistar and Sprague-Dawley rats treated chronically with saline or imipramine. No differences between strains and treatments were observed regarding the Bmax and KD of [3H]prazosin binding sites. The basal levels of cyclic AMP formation were similar in control rats of all strains, but imipramine treatment augmented it significantly in Sprague-Dawley rats. The responses of the cyclic AMP generating system to noradrenaline were significantly lower in Long-Evans than in the remaining strains of rats. Only in Sprague-Dawley rats a significant downregulation of response to noradrenaline was observed after imipramine treatment. All three strains of rats differed significantly among themselves in their responsiveness to isoproterenol; only in Sprague-Dawley rats this response was down-regulated significantly (by 80%) by imipramine treatment.

Animals↗
PubMedDate not supplied

Medium supplementation with zinc enables detection of imipramine-induced adaptation in glycine/NMDA receptors labeled with [3H]L-689,560.

Antidepressant drugs after chronic administration induce adaptive changes in the NMDA receptor complex. Radioligand-receptorbinding studies using [3H]5,7-dichlorokynurenic acid demonstrated a "down-regulation" of the glycine site/NMDA receptor following chronic treatment with antidepressants and electroconvulsive shock. However, binding procedure using this radioligand is time consuming because it requires the use of centrifugation method in the separation process. The introduction of a new radioligand of glycine/NMDA receptor, [3H]L-689,560 enables the application of a rapid filtration method. In the present study we demonstrate that 2-week treatment with imipramine (15 mg/kg ip) did not evoke alterations in specific [3H]L-689,560 binding and in IC50 value of glycine in displacing [3H]L-689,560 binding in the mouse or rat cortex. However, longer, a 4-week treatment with imipramine induced a significant 71% increase in IC50 value in displacing [3H]L-689.560 binding in the mouse cortex. Moreover, the presence of zinc in the incubation media, dose-dependently enhances detection of imipramine-induced increase in IC50 value of glycine in displacing [3H]L-689,560 binding in the rat cortex. The present data indicate that: (1) [3H]L-689,560 may be a suitable ligand for assessing adaptation of the glycine/NMDA sites and (2) the presence of zinc enhances detection of imipramine-induced reduction of glycine affinity for glycine/NMDA receptors labeled with [3H]L-689,560 which further indicates a significance of zinc in the mechanism of antidepressant treatment.

Adaptation, Physiological↗
PubMedDate not supplied

[Comparative effect of chlorpromazine, imipramine and papaverine on the blood platelet function].

With a view of decoding the mechanisms of their action the effect of papaverine, chlorpromazine and imipramine produced on a number of blood platelets hemostatic functions was studied. All the three drugs suppress in a characteristic fashion the aggregation on blood platelets caused by thrombin in the Tyrode solution and in a plasma defibrilated by heating, as well as by collogen and ADP in the citrated plasma. Unlike chlorpromazine and imipramine papaverine exerts a strong inhibiting action on the phosphodiesterase activity. Chlorpromazine and imipramine suppress the absorption of serotonin and retraction more intensively than this is done by papaverine and call forth morphological changes in the blood platelets that proceed parallel with changes in the intensity of the photodiffusion and liberation of endogenous serotonin. It is postulated that chlorpromazine and imipramine manifest their inhibitory effect through nonspecific damage of the blood platelets membranes, whereas papaverine does this through exchange of adenine-nucleotides and, especially, of 3',5'-AMP.

Absorption↗
PubMedDate not supplied

[Comparison of the effect of alprazolam, imipramine and placebo in the treatment of panic disorders in Cali, Colombia].

A comparison of safety, and efficiency of Alprazolam, Imipramine, and placebo in the treatment of panic disorder shows that both active drugs are significantly superior to placebo as regards therapeutic effectiveness. On a 77 patient sample, 62 completed an 8-week treatment, and 66 were considered as "assessable" for efficiency results after completing a 3-week treatment. Significantly, more placebo-treated patients than either Alprazolam, or Imipramine-treated patients dropped out trial, while the number of panic attacks was significantly reduced in both Alprazolam-, and Imipramine-treated groups. When trial was over, 96% of patients in Alprazolam group, and 95% of patients in Imipramine group were free from panic attacks, if compared to 65% in the placebo group. Generally speaking, drugs were well tolerated, and no serious adverse effects or life-threatening events were observed.

Adolescent↗
PubMed1990

Clonazepam and imipramine in the treatment of panic attacks: a double-blind comparison of efficacy and side effects.

Data from 12 patients (in two control study groups) provide preliminary results of an ongoing double-blind comparison of clonazepam and imipramine in the treatment of panic disorder. In both treatment groups, the patients' global improvement was substantial over the first few weeks and persisted over the 6-month treatment period based on assessments by the therapist and the patient; side effects were mild. Faintness was slightly more prevalent among patients on clonazepam treatment but disappeared after the first few weeks. Mild, persistent tachycardia was reported among patients receiving imipramine. No tolerance emerged, and discontinuation was successful in 2 patients from each group after 6 months of treatment. Eight patients needed continued medication (25-50 mg/day of imipramine, 0.5-2.0 mg/day of clonazepam) to maintain substantial improvement. Findings confirm earlier reports from open studies that low doses of both drugs eliminate panic attacks (about 50 mg/day for imipramine and 1.5 mg/day for clonazepam).

Adult↗
PubMed1990

Changes in the sensitivities of dopamine receptors to chronic treatment with imipramine & haloperidol in rats.

Apomorphine induced locomotor activity was studied in Wistar rats treated with imipramine and haloperidol with the help of automated measuring devices. The control rats showed a biphasic response of hypomotility and sedation to low dose apomorphine, and hypermotility to high dose apomorphine. In chronic imipramine-treated rats, the hypomotility and sedative response to low dose apomorphine challenge was significantly attenuated (P less than 0.05), as compared to saline treated controls. A similar response was observed in the chronically haloperidol treated rats (P less than 0.01). However, there were no significant differences in motility responses to high dose apomorphine challenge between the control and experimental groups. These results suggest that presynaptic dopamine auto receptors may not be involved in mediating the loss of response to low dose apomorphine by chronic imipramine treatment. Imipramine being predominantly a monoamine uptake inhibitor and haloperidol a potent postsynaptic D-2 blocker, some indirect mechanisms may be involved in the loss of response to low dose apomorphine challenge.

Animals↗
PubMedDate not supplied

The differential effects of post-session administration of amineptine and imipramine on memory processes in mice.

The effects of post-trial administration of amineptine, a dopaminergic antidepressant drug, were compared with those of memory-facilitating (strychnine, piracetam) or impairing drugs (phenobarbital, imipramine) on an experimental model of memory. Mice were given two sessions in open-field test and the decrease in activity at the second session (habituation) served as an index of retention. The good retention observed with a 1-day inter-session interval was impaired by post-session administration of phenobarbital (10 mg/kg i.p.) or imipramine (5.0 mg/kg i.p.). The poor retention observed with a 5-day inter-session interval was enhanced by post-session administration of strychnine (0.20 mg/kg i.p.), piracetam (1000 mg/kg i.p.) and amineptine (10 mg/kg i.p.). These findings show that different profiles of cognitive and psychomotor effects were produced by imipramine and amineptine. Amineptine, lacking sedative and anticholinergic properties which are characteristic of imipramine, interferes positively with learning and memory, in a manner similar to piracetam and strychnine.

Animals↗
PubMed1990

Sequential combination of imipramine and self-directed exposure in the treatment of panic disorder with agoraphobia.

Thirty-eight patients who had panic disorder with agoraphobia completed 8 weeks of treatment with imipramine followed by 8 weeks of treatment with imipramine combined with behavior therapy consisting of self-directed exposure. Sixty-three percent (24) of the patients responded markedly to this cost-effective combined pharmacologic and behavioral approach. Results also revealed that most of the improvement in panic occurred during the first 8 weeks of treatment when imipramine treatment alone was used, whereas improvement in severity, anxiety, depression, and phobias, in particular, continued to be significant between midtreatment and end of study. Further analysis revealed that improvement in phobic anxiety and avoidance in the first 8 weeks of treatment, rather than improvement in panic, predicted final outcome. Implications of these findings on the complex issue of differential antipanic and antiphobic effects of imipramine are briefly discussed.

Adolescent↗
PubMedDate not supplied

The effect of repeated administration of imipramine, citalopram and mianserin on responsiveness of central serotonergic, alpha 2-adrenergic and cholinergic system in mice.

The effect of antidepressant drugs: imipramine, citalopram and mianserin given either in a single dose or twice a day for 14 days in a dose of 10 mg/kg was investigated in mice in tests for the responsiveness of central serotonergic (L-5 hydroxytryptophan-induced head twitches), alpha 2-adrenergic (donidine hypoactivity) and cholinergic (oxotremorine syndrome) systems. The effect of L-5 hydroxytryptophan was inhibited by repeated administration of citalopram and mianserin but unchanged by administration of imipramine. After a single administration only mianserin inhibited the L-5 hydroxytryptophan effect. Given repeatedly, the investigated antidepressant drugs did not affect the effect of clonidine; only mianserin potentiated the hypoactivity when given in a single dose. Repeatedly administered antidepressant drugs did not affect the action of oxotremorine, although imipramine (but not citalopram or mianserin) antagonized it after a single administration. The results indicate that under the present conditions repeatedly given mianserin and citalopram, but not imipramine, antagonize behavioral effects of L-5 hydroxytryptophan. No one of the investigated antidepressant drugs given repeatedly changed the responsiveness of alpha 2 -adrenergic and cholinergic systems to their agonists. It might be concluded that the changes in alpha 1-adrenergic and dopaminergic systems, observed previously after repeated administration of antidepressant drugs, are selective.

5-Hydroxytryptophan↗
PubMedDate not supplied

The effect of ethanol on arterial blood pressure, central venous pressure and ECG in rabbits treated with the single or multiple dose of amitriptyline or imipramine.

Amitriptyline and imipramine given in the single dose insignificantly depressed the arterial blood pressure but significantly elevated the central venous pressure, prolonged the PQ interval and widened the QRS complex. After a prolonged daily treatment, the subsequent 21st dose of either antidepressant significantly depressed the arterial blood pressure; amitriptyline also depressed the central venous pressure. When given chronically, amitriptyline induced rhythm disturbances and the flattening of T-wave, while imipramine caused the widening of the QRS complex, block of the left bundle branch, changes in the T-wave amplitude, elevation in the ST interval. An intravenous infusion of ethanol potentiated those changes. The impairment of atrioventricular conduction occurred more frequently after administration of ethanol jointly with amitriptyline than with imipramine. Physostigmine salicylate elevated the depressed arterial blood pressure, aggravated the impairment of conduction and potentiated rhythm disturbances caused by the interaction of ethanol with antidepressants. In the above interactions with ethanol imipramine was less toxic than amitriptyline.

Amitriptyline↗
PubMedDate not supplied

[Calcium channel modulators as antidotes in fatal imipramine poisoning].

Calcium entry modulators were tested as antidotes to imipramine lethal toxicity. 42 rats were administered intraperitoneally 85 mg/kg of imipramine. In 6 control rats, hypotension and bradycardia were observed. Survival time was 15' +/- 5'. Survival time of rats treated with intraarterial nitrendipine was 21' +/- 11'. Survival time of 5 out of 6 rats treated by intraarterial verapamil or diltiazem was respectively 19'00" +/- 14'30" and 40'30" +/- 32'00". 5 out of 6 rats treated by intraarterial nimodipine, as well as all of the rats treated by flunarizine or nicardipine survived and were alive and active 48 hours later. Intoxication with imipramine may induce life threatening complications for which there are no specific medication. Nicardipine might be considered in the treatment of acute poisoning by imipramine and related tricyclic compounds.

Animals↗
PubMed1989

Hypersensitivity myocarditis and hepatitis associated with imipramine and its metabolite, desipramine.

We present two cases of myocarditis and hepatitis with histologic characteristics of hypersensitivity-mediated drug reactions associated with imipramine and its metabolite, desipramine. In one case, death was directly attributed to myocarditis; in the second case, the patient died of an acute myocardial infarct, but myocarditis may have played a contributory role. One patient was taking imipramine, and therapeutic concentrations of imipramine and desipramine were documented in postmortem blood. The other patient was receiving desipramine documented by in-patient hospital medication records. Both cases had liver lesions associated in the medical literature with adverse drug reaction to imipramine. Although myocarditis has been previously associated with amitriptyline, these cases appear to be the first reported in association with imipramine/desipramine. The fact that one patient was taking only desipramine suggests that it may be the offending agent.

Aged↗
PubMed1987

Inhibition of 22Na influx by tricyclic and tetracyclic antidepressants and binding of [3H]imipramine in bovine adrenal medullary cells.

In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of 22Na, 45Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. [3H]Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of [3H]imipramine at the same concentrations as they inhibited 22Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of [3H]imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.

Adrenal Medulla↗