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Viloxazine in the treatment of depressive neurosis: a placebo and standard (imipramine) controlled clinical study.

In a 4-week double-blind trial, 33 patients with depressive neurosis were randomly assigned to either viloxazine, imipramine or placebo. Statistically significant improvement was observed in all treatment groups. Imipramine exhibited significant improvement earlier in depressive symptoms, while viloxazine showed significant improvement earlier in anxious symptoms. The same frequency of treatment emergent symptoms occurred in the treatment groups. Premature termination as a consequence of adverse reactions was required in only 1 viloxazine and 1 placebo patient.

Adult↗

Changes in saliva secretion and accommodation width during short-term administration of imipramine and zimelidine in healthy volunteers.

Imipramine at a dose of 75 mg/day, the corresponding dose of zimelidine (100 mg/day) and the full therapeutic dose of zimelidine (200 mg/day) were compared with regard to their anti-cholinergic properties. 20 healthy volunteers participated in a double-blind, controlled, randomized cross-over trial and the effects were evaluated by means of a self-rating scale as well as objective measurements of accommodation width and salivary secretion rate. The test-retest reliability of the methods used was quite satisfactory. The full therapeutic dose (200 mg/day) of the new compound zimelidine could be given in one single dose in the morning without causing more pronounced anti-cholinergic effects than the reference compound imipramine which was given at 25-mg doses three times daily.

Accommodation, Ocular↗

Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline.

Prompted by recognition of the similar structures of riboflavin (vitamin B(2)), phenothiazine drugs, and tricyclic antidepressants, our studies sought to determine effects of drugs of these two types upon the conversion of riboflavin into its active coenzyme derivative, flavin adenine dinucleotide (FAD) in rat tissues. Chlorpromazine, a phenothiazine derivative, and imipramine and amitriptyline, both tricyclic antidepressants, each inhibited the incorporation of [(14)C]riboflavin into [(14)C]FAD in liver, cerebrum, cerebellum, and heart. A variety of psychoactive drugs structurally unrelated to riboflavin were ineffective. Chlorpromazine, imipramine, and amitriptyline in vitro inhibited hepatic flavokinase, the first of two enzymes in the conversion of riboflavin to FAD. Evidence was obtained that chlorpromazine administration for a 3- or 7-wk period at doses comparable on a weight basis to those used clinically has significant effects upon riboflavin metabolism in the animal as a whole: (a) the activity coefficient of erythrocyte glutathione reductase, an FAD-containing enzyme used as an index of riboflavin status physiologically, was elevated, a finding compatible with a deficiency state, (b) the urinary excretion of riboflavin was more than twice that of age- and sex-matched pair-fed control rats, and (c) after administration of chlorpromazine for a 7-wk period, tissue levels of flavin mononucleotide and FAD were significantly lower than those of pair-fed littermates, despite consumption of a diet estimated to contain 30 times the recommended dietary allowance. The present study suggests that certain psychotropic drugs interfere with riboflavin metabolism at least in part by inhibiting the conversion of riboflavin to its coenzyme derivatives, and that as a consequence of such inhibition, the overall utilization of the vitamin is impaired.

Amitriptyline↗

One-year follow-up of hyperactive boys treated with imipramine or methylphenidate.

The authors report on a one-year follow-up of 76 hyperactive boys who had participated in a comparative study of methylphenidate, imipramine, and placebo. They found that there was a higher rate of discontinuance of imipramine than of methylphenidate in this sample and that both medications decreased the boys' rate of weight gain but had no significant effect on growth in height. This findings is of concern because larger doses than were used in this study are in use elsewhere. Teachers reported that the group of boys who had discontinued either medications showed continued hyperactivity and behavior problems in the classroom at one year. The two treatment groups showed continued improvement at one year in classroom and home behavior and did not suffer significantly from each other.

Administration, Oral↗

Electrocardiographic monitoring of enuretic children receiving therapeutic doses of imipramine.

The authors studied the monthly electrocardiographic tracings of 27 children with normal cardiovascular function receiving imipramine therapy for enuresis. They found no substantial EKG changes in any of these children, who were receiving doses of 25 to 75 mg of the drug. They conclude that electrocardiographic monitoring may be essential only when more than 25 to 75 mg of imipramine is given and that it should be established that the patient's cardiovascular function is normal before the drug is administered.

Arrhythmias, Cardiac↗

Prophylactic effect of lithium and imipramine in unipolar and bipolar II patients: a preliminary report.

Relapse rates of the first 35 unipolar and bipolar II manic-depressive patients who entered the controlled phase of a continuing evaluation of the prophylactic value of lithium alone or in combination with imipramine were analyzed. Lithium had a prophylactic effect in unipolar patients and possibly in bipolar II patients. Imipramine did not have a prophylactic effect in either group of patients.

Bipolar Disorder↗

Amoxapine and imipramine in the treatment of depressed outpatients: a controlled study.

In a double-blind, controlled study 158 outpatients with unipolar depression were treated for six weeks with amoxapine, imipramine, or placebo to assess the antidepressant effects of the new dibenzooxazepine compound, amoxapine. Forty-five amoxapine, 43 imipramine, and 27 placebo patients completed at least four weeks of treatment. Active drugs produced significantly more improvement at treatment endpoint, according to several physician-rated measures, but patient-rated measures failed to differentiate among treatments. Both active drugs at daily doses up to 200 mg produced an equal amount of moderate and marked global improvement, and both produced significantly more side effects than did placebo.

Amoxapine↗

Elevated plasma tricyclic levels with therapeutic doses of imipramine.

Nine (15%) of 59 patients treated with imipramine at doses of 150 to 300 mg/day had steady-state plasma levels greater than 500 ng/ml. Low capacity for hydroxylation was found in all six patients for whom hydroxy metabolites were measured. Maximum tricyclic levels in the nine study patients were comparable to levels found in tricyclic antidepressant overdoses (651-2439 ng/ml). No study patient experienced any adverse effects: QRS durations were all less than 100 msec, and a mildly dry mouth was the most commonly reported side effect (five of nine patients). Depressive symptoms recurred in three patients when their imipramine dose was decreased.

Adult↗

Platelet [3H]imipramine binding in affective disorders: trait versus state characteristics.

Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.

Adult↗

Two-year follow-up of exposure and imipramine treatment of agoraphobia.

Sixty-two agoraphobic patient who had completed a controlled study of therapist-assisted in vivo exposure (flooding) and imipramine were assessed 1 month, 6 months, 1 year, and 2 years later. Overall, improvement during treatment was maintained throughout follow-up. At 1 month but not subsequently, imipramine and flooding had significant effects on central measures of agoraphobia. Patients who were marked treatment responders had a favorable clinical course and did not experience secondary depression, unlike patients who had not responded markedly to treatment. These findings suggest that treatments which evoke maximum therapeutic benefit initially are likely to foster long-term maintenance and reduce subsequent depressive sequelae.

Agoraphobia↗

A naturalistic study of imipramine in panic disorder and agoraphobia.

This naturalistic study examined the treatment response to imipramine of 60 patients who had panic disorder or agoraphobia with panic attacks. Only half of the patients could tolerate the drug, but of those who did, 88% obtained a markedly beneficial clinical effect. An amphetamine-like side effect accounted for most of the dropouts. More than one-half of the responders achieved clinical remission at doses (less than or equal to 100 mg/day) and plasma levels (less than or equal to 150 ng/ml) considered to be subtherapeutic for depression. There appears to be neither a clear threshold for response nor a therapeutic dose range for imipramine in the treatment of panic. Doses should be adjusted individually and increased conservatively.

Adult↗

Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders.

Sixty patients with probable atypical depression--defined as meeting Research Diagnostic Criteria for depressive illness, having reactive mood, and having one of four associated symptoms (hyperphagia, hypersomnolence, leaden feeling, and sensitivity to rejection)--took part in a study contrasting phenelzine, imipramine, and placebo. Phenelzine was found to be superior to imipramine and placebo. These results were compared to results from a sample of 120 patients with identical characteristics, except that they had more than one associated atypical symptom (full atypical syndrome). The size of the drug effect was comparable in patients with full atypical and partial atypical syndromes.

Adult↗

Imipramine and social-vocational adjustment in chronic depression.

The authors compared the effects of 6 weeks of imipramine treatment with 6 weeks of placebo treatment on social and vocational impairment in chronic depression. Imipramine was associated with significantly greater pre- to posttreatment improvement of social-vocational impairments in chronic depression, suggesting that these impairments may have represented affective symptoms rather than characterologic deficits.

Adult↗

Imipramine and alprazolam treatment of lactate-induced acute endogenous distress in nonhuman primates.

The authors studied the response of 10 macaque monkeys to administration of sodium lactate, a panicogenic agent used in human panic disorder research, after treatment with the tricyclic antidepressant imipramine, the triazolobenzodiazepine alprazolam, or placebo. Both drugs effectively blocked the lactate-induced acute endogenous distress responses that had been reliably observed in the monkeys before drug treatment. Only alprazolam significantly reduced the occurrence of conditioned situational anxiety responses observed in the home cage. The alprazolam monkeys appeared to be sedated compared to the imipramine and placebo groups, and tremor and temporary exacerbation of anxious behaviors were observed during alprazolam withdrawal.

Alprazolam↗

Imipramine treatment of alcoholism with comorbid depression.

Of 60 depressed alcoholics who completed an open trial of imipramine, 27 (45%) responded with improvement in both mood and drinking behavior, and eight (13%) responded after further dosage increases or treatment with disulfiram. In a subsequent 6-month, randomized discontinuation trial, four of 13 subjects (31%) relapsed during imipramine treatment and seven of 10 (70%) relapsed while taking placebo. This suggests a potential treatment approach for a high-risk subgroup of alcoholics.

Adult↗

Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide in panic disorder patients.

Eleven panic disorder patients who panicked in response to exogenous cholecystokinin tetrapeptide (CCK-4) were rechallenged after chronic treatment with imipramine. In the rechallenge the patients displayed a marked reduction in the number and intensity of panic symptoms, duration of symptoms, frequency of panic attacks, and cardiovascular responsiveness. This study demonstrates that imipramine can antagonize the panicogenic effects of CCK-4.

Adult↗

Oxypertine in combination with imipramine: a controlled trial.

A method for the controlled assessment of two agents for possible interaction in the treatment of endogenous depression is described. This consisted of dose-ranging the supplementary agent (oxypertine 30 mg and 60 mg daily or matching placebo) during Week 2 to Week 6 having established all patients on a therapeutic dose of imipramine during Week 1. The reported enhancement of imipramine by oxypertine was not confirmed.

Adult↗