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PubMed1991

Secondary depression in panic disorder: an indicator of severity with a weak effect on outcome in alprazolam and imipramine treatment.

Depressive symptoms are frequent in panic disorder. Among 123 Scandinavian patients participating in a placebo-controlled multicenter study of the efficacy of alprazolam and imipramine treatment in panic disorder, 21% and 23% fulfilled the DSM-III criteria of current and past major depressive episode, respectively, and 17% had dysthymia, even when melancholia and depressive episode with onset prior to the panic symptoms were excluded. According to a subscale of the Hamilton Rating Scale for Depression (HRSD) with higher validity than the full scale, 18% were classified as major depression and 57% as minor depression. A major finding was that patients with affective symptoms had higher scores on many psychopathological measures, including several Symptom Checklist-90 factors. Accordingly, secondary depression was suggested as an indicator of the severity of panic disorder. Depressed and nondepressed patients significantly improved on major outcome measures, but patients with current minor or major depression improved less. Although the sample was too small for detailed analysis of differences in drug efficacy, there was no indication that imipramine was more effective than alprazolam, considering scores on an HRSD subscale.

Alprazolam↗

PubMed1991

Alprazolam, imipramine and placebo treatment of panic disorder: predicting therapeutic response.

Factors that predicted the outcome of drug treatment (alprazolam or imipramine) of panic disorder were studied in a sample of 123 Scandinavian patients participating in a multicenter placebo-controlled 8-week trial. The attrition rate was 95% for alprazolam, 73% for imipramine and 46% for placebo. For the intention-to-treat and 3-week-completer samples, drugs and anxiety symptoms at baseline were the best predictors of improvement on the Global Improvement Scale and on symptom scales focusing on panic attacks, phobic behavior and anticipatory anxiety. For completers of the 8-week trial, only baseline scores predicted outcome. Generally, more severe symptoms at baseline predicted a worse outcome. A subsample of patients had a marked placebo response. Avoidance, sex, age, childhood psychopathology and previous treatment experience had no or only a weak impact on the outcome. The relationship between panic disorder and mood disorder is presented elsewhere.

Adult↗

PubMed1991

Aggression, hyperactivity and platelet imipramine binding.

We measured platelet 3H-imipramine binding parameters in 16 subjects affected by different types of mental deficiency, all characterized by hyperactive and/or aggressive behaviour, and in 16 healthy controls. The patients had a lower maximum binding capacity than the controls, with no difference in Kd, irrespectively of the type of mental disorder. These findings suggest a link between 5-HT disturbances, reflected by reduced imipramine binding sites, and behavioural dyscontrol, expressed as hyperactivity and aggression.

Adult↗

PubMed1992

Platelet 3H-imipramine binding during recovery from depression.

Decreased binding of tritiated imipramine to platelets has been considered to be a potential biological marker of depression. However, it has been unclear how binding values alter during treatment and recovery. This study investigated imipramine binding parameters and depressive symptoms in 25 patients suffering from major depression at entry to the study and 1, 3 and 6 months later. Although the initial Bmax values were significantly lower in the depressed patients than in healthy subjects, it was not possible to establish a clear relationship between recovery from depression and Bmax. The power of this study to detect an effect of at least 10% of the variance in Bmax due to factors related to recovery from depression was 0.78.

Adult↗

PubMed1981

Qualitative changes in saliva composition after short-term administration of imipramine and zimelidine in healthy volunteers.

Ten healthy volunteers participated in a double-blind controlled, randomized, cross-over trial, where the effects of the antidepressant drugs imipramine (75 mg/day) and zimelidine (100 mg/day and 200 mg/day) on saliva secretion rate and saliva composition were tested. The saliva secretion decreased and qualitative changes were found. Imipramine (75 mg/day) and zimelidine (200 mg/day), but not zimelidine (100 mg/day), increased buffer capacity and the components of the salivary glycoproteins (sialic acid, fucose, hexoses). Total proteins, amylase, secretory component and electrolytes (Na+, K+, Ca++, PO43-) did not change significantly.

Adult↗

PubMed1982

Equilibrium dialysis for determination of protein binding or imipramine--evaluation of a method.

A range of methodological problems associated with equilibrium dialysis for serum or plasma protein binding assay of a weakly basic drug imipramine, in man has been carried out in order to establish a reliable procedure for large scale studies. Freezing of serum samples did not change the binding significantly, but a slight tendency towards increased binding to samples stored for 30 days was found. Protein binding was significantly higher in serum than in heparinized or citrated plasma, whereas there was no significant difference between plasma obtained by use of heparin or citrate as anticoagulant. There was a linear correlation between temperature (25-42 degrees) and binding such that binding decreased 0.1% per centigrade increase in temperature. Increase in pH resulted in increase in binding (0.6% per 0.1 unit pH). Equilibrium between serum and buffer phase was obtained within 5-6 hrs. The changes following osmotic equilibrium necessitated volume corrections of about 4-5% after 5-6 hrs, and 20-25% after 16-20 hrs (overnight experiments). With this correction the free fraction estimate remained constant for 26 hrs. Application of small volumes in the dialysis chamber may make the volume correction difficult and inaccurate. The use of Tris-Ringer buffer gave free fraction values about 20% higher (absolute values of free fraction) than that with phosphate buffer. With different imipramine concentrations a constant degree of binding was found at "therapeutic" levels, whereas a significantly decreased binding was found at a concentration of 1000 ng/ml. Control of these methodological factors is a prerequisite for obtaining reproducible and valid results, and authors should give more details on methodology in this field.

Blood Proteins↗

PubMed1984

Attenuation of the post-decapitation convulsions after repeated treatment of rats with desipramine, imipramine and maprotiline.

The effects of repeated treatment of rats with the antidepressant or potential antidepressant agents alaproclate, citalopram, clomipramine, desipramine, imipramine, maprotiline, mianserin and zimeldine on the convulsions released by decapitation were examined. The noradrenaline uptake inhibitors desipramine, imipramine and maprotiline increased significantly the latency of onset of the post-decapitation convulsions (PDC's) after repeated administration of 10 mumol/kg orally twice daily, or 66 mumol/kg orally once daily (desipramine), for 15 days. The duration of the PDC's was slightly prolonged by these agents. A single acute dose of desipramine (20 mg/kg) administered at various time intervals before decapitation (1 to 24 hours) had no effect on the PDC's nor did repeated treatment with the other compounds examined, alaproclate, citalopram, clomipramine, mianserin and zimeldine, have any effect upon the PDC latency. The results are interpreted as evidence for noradrenaline receptor subsensitivity following chronic treatment.

Alanine↗

PubMed1977

Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats.

Imipramine and clomipramine were administered to rats by the oral and intramuscular routes as single and multiple doses. The concentrations of both drugs and their active demethylated metabolites desipramine and desmethylclomipramine were measured in blood plasma, blood cells and brain. The concentrations of the metabolites were higher and the concentrations of the parent substances lower after oral than after parenteral administration, both in blood and in brain. In brain imipramine, despiramine and clomipramine during continuous treatment exceeded their plasma concentrations by six to ten times. The corresponding figure for desmethylclomipramine was 1-7. The extent of accumulation of the investigated substances in the brain was independent of the route of administration.

Administration, Oral↗

PubMed1984

The production and properties of gel precipitated aluminium hydroxide spheres containing imipramine.

The production of aluminium hydroxide spheres containing imipramine by gel precipitation of liquid feed solutions has been described. Washing and heating procedures applied to the precipitated spheres markedly affected the rate of drug release from the spheres into 0.1M hydrochloric acid. Increasing the imipramine content of the spheres also altered the drug release rate. The effects described have been explained with reference to model theories of the precipitation and ageing of aluminium hydroxide gels in the presence and absence of 'foreign' anions.

Aluminum Hydroxide↗

PubMed1987

Some factors affecting the release of imipramine from gel-precipitated aluminium hydroxide spheres.

Changing the pH of the dissolution medium has been found to affect the release of imipramine from gel-precipitated aluminium hydroxide spheres. Release from unwashed, unheated spheres into solutions of pH 1.2 was controlled by dissolution of the gel matrix, whereas that into solutions of pH 3 and pH 5 appeared to be under diffusion control. The liberation of drug from unwashed, heated spheres into the media of higher pH exhibited more complex kinetics. Washed spheres failed to release significant amounts of imipramine into the solutions of pH 3 and 5. Changing the ionic strength of the media had little effect on drug release. These phenomena have been explained with reference to model theories of the precipitation and ageing of aluminum hydroxide gels and their pH-solubility profiles.

Aluminum Hydroxide↗

PubMed1988

Repeated treatment with imipramine and amitriptyline reduced the immobility of rats in the swimming test by enhancing dopamine mechanisms in the nucleus accumbens.

Bilateral injections of 1 microgram sulpiride in the rat nucleus accumbens antagonized the effect of a seven-day treatment with 20 mg kg-1 day-1 imipramine or amitriptyline in the swimming test. The data suggest that dopamine mechanisms in the limbic regions of the rat brain are involved in the effect of repeated treatment with imipramine and amitriptyline in that test.

Amitriptyline↗

PubMed1982

Different synaptic location of mianserin and imipramine binding sites.

The high-affinity binding sites for mianserin and imipramine appear to be locate in different neurons of rat brain. Studies in which lesions were produced with 5,7-dihydroxytryptamine and other studies in which the 5-hydroxytryptamine content was decreased with p-chlorophenylalanine indicate that some of the imipramine binding sites are on serotonin axon terminals and others are on nonserotonergic synapses. The sites that bind mianserin are on postsynaptic serotonin sites as well as on synapses of other neuronal systems.

5,7-Dihydroxytryptamine↗

PubMed1982

Tritiated imipramine binding sites are decreased in the frontal cortex of suicides.

Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder.

Adolescent↗

PubMed1980

Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients.

The high-affinity binding of triatiated imipramine to platelet membranes was compared in samples from 16 untreated depressed women and 21 age-matched controls of the same sex. The maximal binding in the depressed group was significantly lower than that of the controls, although the affinity constants were similar. These results suggest that binding of tritiated imipramine in human platelets may represent a biochemical index of depression, possibly reflecting similar changes in the brain.

Adult↗

PubMed1978

Diagnosis of phaeochromocytoma after ingestion of imipramine.

An 11-year-old twin girl was admitted to hospital with a 24-hour history of profuse sweating, tachycardia, and hypertension after a single dose of imipramine. She was subsequently found to have a right adrenal phaeochromocytoma. To our knowledge, this is the first reported case of tumour provocation by imipramine.

Adrenal Gland Neoplasms↗

PubMed1982

Controlled trial of imipramine in diurnal enuresis.

Twenty-seven children with diurnal enuresis were studied in a double-blind randomised controlled trial of imipramine. Outcome was not related to such features as age, gender, maximum functional bladder capacity, or evidence of psychiatric disturbance. Although the condition in several children improved, no evidence emerged to suggest that imipramine was superior to placebo in the treatment of the condition.

Child↗

PubMed1988

Acrocyanosis due to imipramine.

An 11 year old girl who was being treated for enuresis with imipramine developed acrocyanosis of the hands and feet. All biochemical and haematological investigations gave normal results. When imipramine was stopped the girl recovered within three days.

Adolescent↗

PubMed1970

Depressive illness in a general practice. A demographic study and a controlled trial of imipramine.

The distribution of 93 consecutive cases of depressive illness in a Surrey general practice was found to be non-random. Married women were at risk, while men and unmarried women were largely spared. Married women were prone to the disorder at any time in their lives, and relapse was frequent. There was some suggestion that divorced wives and wives of low social class were particularly predisposed to the disorder.Sixty of the patients took part in a double-blind controlled trial of imipramine. There was no evidence that the drug was superior to a placebo in inducing a remission. It is suggested that imipramine has become established in clinical practice on inadequate evidence and that there is a need for further trials.

Adolescent↗