Plasma levels and antidepressive effect of imipramine

Abstract

The relationship between the antidepressive effect of imipramine and the plasma concentrations of imipramine and the active metabolite desipramine was studied in 24 patients suffering from endogenous depression. After a placebo period of 7 days, the patients received imipramine, 75 mg 3 times a day. The dose was reduced in patients with pronounced side effects. Blood samples for drug assay were drawn in the morning, 15 hr after the last drug intake. Imipramine and desipramine in plasma were assayed by quantitative in situ thin-layer chromatography. Individual variations in plasma concentration were 20- to 30-fold in both imipramine and desipramine. Severity of depression was assessed on the Hamilton Rating Scale (HRS). Eleven of 12 patients who responded satisfactorily to the treatment (HRS post-treatment score less than 8) had plasma concentration of imipramine greater than or equal to 45 mug/L, and desipramine greater than 75 mug/L, whereas the 12 patients not responding satisfactorily (post-treatment score on HRS greater than or equal to 8) all had concentrations of imipramine or desipramine or both below these limits.

Pharmacokinetics of methylphenidate in hyperkinetic children.

“…Within the area of psychiatric disturbances, measurement of plasma levels of the tricyclic antidepressants promises to provide more effective clinical management of depression as well as understanding and classification of the heterogenous disorders classified as depression (Braithwaite, Goulding, Theano, Barley & Coppen, 1972;Glassman, Perel, Shostak, Kantor & Fleiss, 1977;Gram, Reisby, Ibsen, Nagy, Dencker, Peterson & Christiansen, 1976;Kragh-Sorenson, Asberg & Eggert-Hansen, 1973).…”

Plasma levels and clinical response with imipramine in a study comparing efficacy with mianserin and nomifensine.

“…It therefore seems that the association between higher levels and better response which has been reported (Glassman & Perel, 1973;Gram et al, 1976;Reisby et al, 1977) is still open to question. Some of these studies have methodological flaws, for example, the use of flexible dosages which confuses the relationship between levels and response, and in the study of Glassman & Perel (1973), the retrospective exclusion of severely depressed psychotic patients.…”

“…It is worth stressing that 36% of the patients treated with 75mg imipramine developed levels of imipramine above the cut-off suggested by Gram et al (1976). In the second study using a dose of 150mg imipramine, 73% of patients developed levels above the cut-off.…”

A Comparative Pharmacodynamic Study of the Arrhythmogenicity of Antidepressants, Fluvoxamine and Imipramine, in Guinea Pigs.

“…With regard to IMI, the minimum plasma concentration required to induce antidepressive effects was reported to be 45 ng/ml, while there is a large degree of interpatient variability in the pharmacokinetics and a 20-to 30-fold range is possible for plasma IMI concentrations. 19) Indeed, even under a therapeutic dosage regimen of 225 mg/d, some patients experienced a plasma IMI concentration of 200-250 ng/ml. 19) Therefore, the maximum therapeutic concentration of IMI is considered to be approximately 300 ng/ml.…”

“…19) Indeed, even under a therapeutic dosage regimen of 225 mg/d, some patients experienced a plasma IMI concentration of 200-250 ng/ml. 19) Therefore, the maximum therapeutic concentration of IMI is considered to be approximately 300 ng/ml. The maximum concentrations of IMI and FLV in this study were 3.94 and 2.02 mg/ml, which correspond to the 13-and 20-folds of the aforementioned concen- trations considered to be therapeutic in humans.…”