The paper describes the effect of
metyrapone supplementation on
imipramine therapy in patients (with treatment-resistant
unipolar depression) who fulfilled DSM IV criteria for major depression. Nine patients were enrolled to the study on the basis of history of their illness and
therapy. Following 2 weeks of washout period, the patients were treated with
imipramine twice daily (100 mg/day) for 6 weeks, and then
metyrapone was introduced (twice daily, 500 mg/day), and administered jointly with
imipramine for further 6 weeks. Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of
antidepressant therapy.
Imipramine changed neither HDRS nor BDI score after 6 weeks of treatment when compared with baseline (before treatment).
Metyrapone supplementation significantly reduced both HDRS and BDI scores after 6-week supplementation. Moreover, pharmacokinetic data indicate that
metyrapone did not influence significantly the plasma concentration of
imipramine and its metabolite,
desipramine in the patients during joint treatment with
metyrapone and
imipramine, what suggests the lack of pharmacokinetic interaction. This preliminary study is the first demonstration of the benefit of
metyrapone supplementation in
imipramine therapy of treatment-resistant
unipolar depression and suggests that a change in the level of
neurotransmitters,
hormones and immunological parameters, which are disturbed in depression, may contribute to the mechanism of the action of this
drug.