Metabolism, anticholinergic effects, and therapeutic outcome of desmethylimipramine in depressive illness

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Abstract
Synopsis: In order to test two theories of the mode of action of imipramine 58 depressive patients were treated at two dosage levels with desmethylimipramine (DMI), its active metabolite. Clinical judgments were used to distinguish therapeutic responders from non-responders, who showed clear differences in depressive rating scales and body weight changes. Measurements of urinary output of DMI, of salivation, and of the incidence of side-effects were compared in responders and non-responders: no differences appeared between the two groups. It is concluded that the therapeutic effect of imipramine does not depend on either its anticholinergic or other action revealed by the common side-effects, and that variability of response cannot be accounted for by differences in the rate of metabolism of DMI.