Imipramine In Patients Research Articles

Plasma protein binding of imipramine in patients with rheumatoid arthritis

In 23 patients with rheumatoid arthritis the plasma protein binding of 3H-imipramine and the plasma levels of 13 proteins were measured in order to examine the significance of the proteins for the binding of imipramine. The degree of 3H-imipramine binding did not differ significantly from that in healthy controls. It was positively correlated with the concentrations of fibrinogen, alpha 1-acid-glycoprotein, ceruloplasmin, complement C3c, haptoglobin and hemopexin. Erythrocyte sedimentation rate was also highly positively correlated with binding. The concentration of several of the proteins showed a significant covariation. The 3H-imipramine binding was negatively correlated with the concentration of albumin and the latter was negatively correlated with some of the proteins mentioned-above. No correlation with the levels of apolipoproteins A and B was found. There appears to be more a qualitative than a quantitative change in 3H-imipramine binding in patients with rheumatoid arthritis.

A double‐blind clinical trial of fluvoxamine and imipramine in patients with primary depression

AbstractFluvoxamine, a new serotonin‐reuptake inhibitor, and imipramine were compared under double‐blind conditions in 36 unipolar and bipolar depressed inpatients. Both drugs produced significant reductions in depressive symptomatology over a 4–6‐wk course of treatment, with the greater part of the improvement occurring in the first 2 wk. No statistically significant differences were obtained between the two drugs. Adverse reactions, particularly anticholinergic ones, were much less frequently observed in the fluvoxamine group. No clinically significant laboratory abnormalities were reported for either treatment; but minor ECG irregularities were seen under both treatments. The findings generally correspond to results obtained in previous comparative clinical trials.

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.

Treatment of Depression-Reply

In Reply.— These letters suggest the need for explicit clarification of certain issues implicit in my editorial entitled Depressives, Doctors, and Antidepressants. Doubtless there would be general agreement that chlordiazepoxide is [not] preferentially indicated compared with imipramine in patients who have been depressed for at least three months, with a Hamilton test score of 25 or higher, probable or definite endogenous syndrome, and required admission as inpatients. The question is how faithfully this description, the sample studied by Keller et al, and the patients seen by investigators in tertiary-care centers generally represent depressed persons in the community who do not contact the medical care system or who are seen by primary care physicians. Systematic information about this point apparently is not yet available. Conversations with research psychiatrists who have long experience in working with family physicians suggest that depressed persons seen in primary care settings tend to be less severely

Changes in visual evoked potentials induced by imipramine in patients with endogenous depression.

Changes in visual evoked potentials induced by imipramine in patients with endogenous depression.

Comparisons of Maprotiline with Imipramine in Severe Depression: A Multicenter Controlled Trial

The efficacy and safety of maprotiline (Ludiomil) was compared to imipramine in patients with manic-depressive illness, depressed type (DSM II 296.2). Three hundred forty-one patients from 16 different centers entered this four-week double-blind controlled trial, with 171 in the maprotiline and 170 in the imipramine group. Efficacy measurements included the Hamilton Depression Scale, the Self-Rating Depression Scale, and the Investigator's Overall Assessment of Effectiveness. Tolerability was monitored by collection of treatment-emergent signs and symptoms (TESS), blood pressure and pulse measurements, EKGs, and EEGs. Dosage was fixed for the first week at 50 mg t.i.d. and thereafter could be varied between 50 and 300 mg daily. Clinically and statistically significant reductions in symptomatology were noted in both drug groups for most efficacy parameters at each visit during therapy. Comparison between the drug groups revealed no difference in terms of the scales utilized. A trend toward fewer TESS in the maprotiline group was noted, especially for the side effects nausea, nervousness, and increased sweating.

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.

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 μg/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 μg/l, DMI: 24–659 μg/l and IP+DMI: 58–809 μg/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.