Abstract
Sixty-six hospitalized depressed patients were treated for 4 weeks with imipramine (Tofranil®) 225 mg/day. Blood samples were drawn twice weekly 15 h after the last drug intake, and IP and DMI concentrations in plasma were assayed by quantitative in situ thin-layer chromatography. Clinical rating was carried out once weekly by Hamilton's Rating Scale (HRS), Beck's Depression Inventory, WHO Depression Scale (Quantitative Part), and a side-effect scale. The patients were classified on the basis of the WHO Depression Scale (Qualitative Part) as ‘endogenous’ (N=37) or ‘non-endogenous’ depressions (N=29). Antidepressive effect was evaluated on the basis of the posttreatment rating scores.
In patients classified as ‘endogenous’ depressions all 12 responding patients (HRS≦7) had plasma levels of IP>45 μg/l and DMI>75 μg/l, whereas 11 out of 14 nonresponding patients (HRS≧16) had plasma levels of one or both compounds below these limits. Ten out of 12 responders had levels of IP+DMI above 240 μg/l, and all nonresponders had levels of IP+DMI below this limit. Patients with partial response (HRS: 8–15) formed an overlapping group. There was no sign of an upper plasma level limit for the antidepressive effect of imipramine.
The plasma level/effect relationship was less clear in patients with ‘non-endogenous’ depressions, since several of them responded at low plasma levels.
Some relationship between effect on blood pressure (orthostatic effect) and high plasma levels of IP and DMI was found.
Using a plasma level limit of IP≷45 μg/l and DMI≷75 μg/l, it was possible to predict the response of the ‘endogenous’ depression group for 10 out of 12 responders and 10 out of 14 nonresponders on the basis of plasma level measurements obtained after 1 week of treatment.
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Reisby, N., Gram, L.F., Bech, P. et al. Imipramine: Clinical effects and pharmacokinetic variability. Psychopharmacology 54, 263–272 (1977). https://doi.org/10.1007/BF00426574
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DOI: https://doi.org/10.1007/BF00426574