Use Of Imipramine Research Articles

Pediatric Cardiovascular Effects of Imipramine and Desipramine

Electrocardiograms were evaluated in 39 children and adolescents before and after the clinical use of imipramine and desipramine. The average increase in PR interval was 0.01 seconds. The PR interval increased by 0.02 seconds in 11 subjects, and a new first-degree atrioventricular block developed in two subjects. These changes were not related to the choice between imipramine and desipramine, the dose, or the method of administration. An increase in PR interval by 0.02 seconds or more did correlate with having an abnormality disclosed on a pretreatment electrocardiogram. The average increase in PR interval was 0.007 seconds for subjects with normal baseline electrocardiograms and 0.019 seconds for subjects with conduction and nonconduction abnormalities disclosed in baseline tracings. None of the electrocardiogram changes resulted in adverse clinical consequences.

The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms

The effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a randomised, double-blind, cross-over study. Paroxetine was given as a fixed dose of 40 mg/day, while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400–600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer- and self-rating, but was somewhat less effective than imipramine. However, patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs. On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study reported withdrawal symptoms after discontinuing imipramine. On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported. Self-rating showed no depressive symptoms at baseline, and no changes during the study. Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function. In conclusion, 40 mg paroxetine/day significantly reduced the symptoms in peripheral diabetic neuropathy and it was suggested that by dose adjustment on the basis of drug level monitoring, paroxetine may become as effective as imipramine. Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients.

Treatment of severe imipramine poisoning complicated by a negative history of drug ingestion

The wide use of imipramine (Tofranil) for the treatment of nocturnal enuresis continues in spite of the unique dangers associated with this drug. Young children are particularly susceptible to the potentially lethal central nervous system and cardiovascular toxicities, yet the toxic potential of imipramine remains unrecognized by both parents and too many physicians. Management of severe imipramine intoxication can be difficult. This report describes a 12-month-old patient with severe imipramine intoxication whose treatment was complicated by a negative history at presentation.

Amfebutamone: does not produce cardiovascular side effects whereas the use of imipramine is limited by hypotension

Amfebutamone: does not produce cardiovascular side effects whereas the use of imipramine is limited by hypotension

Tricyclic Antidepressants in the Treatment of Children with Attention Deficit Disorder

The controversy over the use of imipramine and other tricyclics in the treatment of attention deficit disorder (ADD), is examined, and all available literature is critically reviewed. Although both stimulants and antidepressants ameliorate ADD symptoms, the bulk of the literature suggests that overall, stimulants are superior to imipramine in the treatment of ADD. There may, however, be a subgroup of children with ADD who respond better to imipramine, and this group may be one characterized by higher levels of anxiety or depression or both.

Drug interaction of imipramine hydrochloride to the pharmacodynamics and pharmacokinetics of oxazepam

In this report, we studied drug interaction between oxazepam and imipramine in rats. Oxazepam (20 mg/kg) and imipramine (20 or 50 mg/kg) were administrated orally. The oxazepam concentration in plasma, brain and liver were measured by the method of HPLC. The concomitant use of imipramine induced extension of the elimination half life (T 1/2 beta) and an increase of the area under the concentration time-curve (AUC) on the plasma concentration of oxazepam. With the concomitant use of imipramine, the AUC of oxazepam brain concentration increased approximately 1.42 to 1.56 in contradistinction to oxazepam alone. The anti-pentylenetetrazol effect of oxazepam at 1 hr after administration was increased by the concomitant use of imipramine, but there were no combination effects at 4 hr. The motor incoordination effect of oxazepam and diazepam was measured by the rotarod method. Oxazepam has little effect on the motor incoordination as compared with diazepam. The plasma protein binding of oxazepam was not changed by the combined use of imipramine both in vitro and in vivo. The pharmacodynamic effects of oxazepam were increased by the concomitant use of imipramine, and these effects were in reasonably good agreement with the change in brain concentration of oxazepam.

Hypertension in Neuroblastoma Induced by Imipramine

Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.

The use of imipramine in minor motor seizures

A study is presented of 15 pediatric patients treated with imipramine for uncontrolled seizures during the past two years. Of these patients, 53% had an initial reduction of seizures of greater than 80%. At one year, 26% were still seizure-free. Drop attacks were especially responsive to therapy; 100% ( 7 7 ) responded initially to imipramine therapy. Most patients studied had been receiving valproate and another major antiepileptic drug prior to imipramine therapy. This study confirms previous reports and suggests that the use of imipramine in combination with other antiepileptic drugs provides excellent results, particularly in patients with drop attacks.

Orthostatic Effect of Imipramine and Doxepin in Depressed Geriatric Outpatients

Blood pressure measurements were collected from 36 depressed geriatric outpatients (ages 55 to 81 years) enrolled in a double-blind, placebo-controlled study of the efficacy of doxepin and imipramine. Mean systolic postural changes were 25.9 mm Hg for imipramine, significantly higher than the 10.5 mm Hg for doxepin, and 12.4 mm Hg for placebo. The orthostatic drop in the imipramine group was only weakly related to dose and did not correlate with amount of pretreatment orthostatic hypotension or with duration of treatment. The increased orthostatic hypotension occurred early in treatment and at low doses of imipramine. Accordingly, caution is advised in the use of imipramine for the elderly.

The metabolism and excretion of [14C]imipramine in an experimental hepatitis.

The effect of experimental hepatitis, induced by i.p. D-galactosamine, on the metabolism and excretion of [14C]imipramine in the rat is reported. The major consequence was an increase of the conjugated metabolites of imipramine excreted in urine, resulting in a four-fold increase in 2-hydroxyimipramine glucuronide and two-fold increases in 2-hydroxydesmethylimipramine glucuronide and 10-hydroxyimipramine glucuronide. The total excretion of 14C-labelled metabolites in urine of galactosamine-treated rats was 69% dose compared with 37% in untreated animals. Faecal excretion of [14C]imipramine metabolites was lowered from 68% dose in untreated animals to 27% in animals with induced hepatitis. Induction of a galactosamine hepatitis decreased markedly the biliary excretion of imipramine metabolites in bile duct-cannulated rats; 80% dose was excreted in bile in normal rats, and 35.5% in rats with hepatitis. Plasma clearance of imipramine, after i.v. dosage, was decreased by 60% and clearance of metabolites (excluding imipramine) by 40%, in galactosamine hepatitis; the pharmacokinetics changed from a two- to a single-compartment system reflecting decreased extraction and/or metabolism, by the liver. The clinical implications of these findings are discussed in relation to the hazard attending the use of imipramine in patients suffering from liver disease.

The Use of Imipramine in Depressed Patients With Congestive Heart Failure

Previous studies of left ventricular performance (LVP) in depressed patients receiving tricyclic antidepressants have been performed on patients without severe heart disease. This study reports the effect of imipramine hydrochloride on LVP, assessed by radionuclide angiography, in a group of depressed patients with notable preexisting left ventricular dysfunction. Ejection fraction was measured at rest by first-pass radionuclide angiography before and after treatment with imipramine. Ejection fraction was unchanged during treatment, but seven of 15 patients experienced orthostatic hypotension of such severity that administration of the drug had to be discontinued. Plasma concentrations of the drug were essentially twice those usually seen. It is important to appreciate that although imipramine does not further impair resting LVP, this does not mean it is without risk. The physician must watch carefully for orthostatic hypotension when using imipramine in depressed patients with impaired LVP.

The use of imipramine in depressed patients with congestive heart failure

Previous studies of left ventricular performance (LVP) in depressed patients receiving tricyclic antidepressants have been performed on patients without severe heart disease. This study reports the effect of imipramine hydrochloride on LVP, assessed by radionuclide angiography, in a group of depressed patients with notable preexisting left ventricular dysfunction. Ejection fraction was measured at rest by first-pass radionuclide angiography before and after treatment with imipramine. Ejection fraction was unchanged during treatment, but seven of 15 patients experienced orthostatic hypotension of such severity that administration of the drug had to be discontinued. Plasma concentrations of the drug were essentially twice those usually seen. It is important to appreciate that although imipramine does not further impair resting LVP, this does not mean it is without risk. The physician must watch carefully for orthostatic hypotension when using imipramine in depressed patients with impaired LVP. (<i>JAMA</i>1983;250:1997-2001)

Differential treatment of phobias: Use of imipramine for panic attacks

The core disorder in agoraphobia and mixed phobia typically is the “spontaneous” panic attack, which may be due to various psychologic and physiologic triggering mechanisms. The panics tend to lead to anticipatory anxiety and, consequently, avoidance behavior. Tricyclics and MAO inhibitors suppress the spontaneous panics. Once this is accomplished, psychotherapeutic intervention helps patients overcome their phobias. Supportive psychotherapy, imaginal desensitization and in vivo exposure appear to be equally effective. Phobics who do not experience spontaneous panics are unaffected by these drugs but improve with psychotherapeutic techniques.

An indication for use of imipramine in attention deficit disorder.

Many children with attention deficit disorder also meet DSM-III criteria for separation anxiety disorder, the symptoms of which cluster in four of the nine criteria. In a study of 14 boys with both diagnoses, the attention deficit disorder of every boy responded to imipramine.

EKG Effects of Imipramine Treatment in Children

Their are increasing reports of serious side effects in children with clinical use of imipramine in high doses. Our analysis of the EKG effects of imipramine in 25 hyperactive and 8 school phobic children suggests that children on a dose of imipramine of 3.5 mg/kg or more are likely to show an increase in PR interval of .02 seconds or more and that such increases are more likely to occur in patients with a small pretreatment PR interval. In 7 children the PR interval prolongation was above the rate-corrected norm. EKG monitoring seems desirable in children maintained on imipramine dose of 3.5 mg/kg or more.

EKG Effects of Imipramine Treatment in Children

There are increasing reports of serious side effects in children with clinical use of imipramine in high doses. Our analysis of the EKG effects of imipramine in 25 hyperactive and 8 school phobic children suggests that children on a dose of imipramine of 3.5 mg/kg or more are likely to show an increase in PR interval of .02 seconds or more and that such increases are more likely to occur in patients with a small pretreatment PR interval. In 7 children the PR interval prolongation was above the rate-corrected norm. EKG monitoring seems desirable in children maintained on imipramine dose of 3.5 mg/kg or more.

Toxicological evaluation of imipramine in combination with adriamycin and strophanthin.

Chronic oral administration of imipramine to rats caused characteristic changes of the electrocardiogram (ECG), i.e. prolongation of the PR interval, widening of the QRS complex, and increase in T-wave voltage. The cardiotoxic anthracycline antibiotic adriamycin induced dose-dependent widening of the QRS complex. This effect on intraventricular conduction was not enhanced in rats receiving both drugs. The high adriamycin dose (5 x 4 mg/kg) abolished imipramine-induced prolongation of the PR interval and T-wave elevation. This was not seen with the low adriamycin dose (20 x 1 mg/kg). Imipramine prolonged survival time of rats treated with toxic doses of adriamycin, but enhanced growth retardation in animals receiving the low adriamycin dose. Chronic treatment with increasing doses of strophanthin induced significant flattening of the T wave in rats with and without imipramine therapy, but did not influence the changes of the ECG or body weight gain caused by imipramine. It is concluded that the combined use of imipramine and adriamycin or strophanthin did not lead to a serious enhancement of the toxicity of the tricyclic antidepressant.

Psychogenic Encopresis Treated With Imipramine

To the Editor.— In their list of therapeutic indications of imipramine hydrochloride (Tofranil, Presamine), the companies' package inserts include psychogenic enuresis but not the related condition of psychogenic encopresis. I know of only two reports 1,2 and of no controlled studies concerning the use of imipramine in the treatment of psychogenic encopresis. Both reports suggest that imipramine can be of value in the treatment of this condition. Recently, I treated a child with chronic, continuous, nonretentive psychogenic encopresis, which subsided rapidly after imipramine treatment. Report of a Case.— A 9-year-old boy was referred for psychiatric evaluation because of chronic fecal soiling, after a thorough medical work-up on two different occasions did not show any organic illness responsible for this condition. The soiling began at the age of 3 1/2 years, a few months after the family emigrated from Greece to the United States and at about the time that his

Pharmacotherapy and Management of Pathological Separation Anxiety

In the history of child psychiatry, pharmacological intervention has followed practice established with adults. This approach is eminently rational because of the reluctance to administer to developing organisms compounds whose effects are not well known in mature humans. Thus, after antipsychotic, antidepressant, and stimulant drugs were found to have valuable properties in adults, they were tried among similar, child, clinical groups. Though the use of imipramine in school-phobic children followed its use in agoraphobic adults (Klein, 1964; Klein & Fink, 1962), its first application was derived from inferences regarding relationships of psychopathology rather than from strict, therapeutic empiricism. The syndrome of agoraphobia was clearly identified long ago, but until recently had received relatively little clinical attention. Agoraphobic adults experience sudden, unexplained, panic attacks and are unable to travel independently. They are typically women. One, Freudian theory posits that the symptoms are due to an unconscious, anxiety-provoking, prostitution wish: the women's phobic avoidance of the outside world prevents the activation of an incompletely repressed wish to be a streetwalker. Fortuitously, Klein discovered that imipramine blocked agoraphobes' apparently spontaneous panic attacks. Double-blind, placebo-controlled studies confirmed this clinical finding (Klein, 1964). Applying an ethological concept to the panic anxiety of agoraphobes, Klein postulated that these patients suffered from a disruption of a normal biological process responsible for the regulation of anxiety triggered by separation. This notion was stimulated by the observation that a large proportion of the patients had a childhood history of severe separation anxiety and that their

Modern Perspectives in International Child Psychiatry

This volume is one of three in the series, Modern Perspectives in Psychiatry. Two of the volumes, including the one here reviewed, are devoted to child psychiatry. A variety of subjects is discussed helpfully, starting with intrauterine hazards, through birth and early infancy, to mother-child and father-child relations. The clinical part includes discussion on electrocerebral activity and sleep disturbances, psychosomatic conditions, psychogenic retardation and organic psychosis. A comprehensive discussion of school problems and residential care of children is followed by a very interesting article on the strategy of follow-up study, which is so important in improving our ability to better predict the outcome of emotional problems in childhood. However, the word modern, in the title, promises more than it fulfills. Indeed, although this book is comprehensive and includes a variety of important topics, much new information is missing, eg, the use of imipramine in enuretic children, or the salutary effects