The paper describes the effect of
amantadine addition to
imipramine therapy in patients suffering from treatment-resistant
unipolar depression who fulfilled DSM IV criteria for major (
unipolar) depression. Fifty patients were enrolled in the study on the basis of their histories of illness and
therapy. After a 2-week
drug-free period, 25 subjects belonging to the first group were treated only with
imipramine twice daily (100 mg/day) for 12 weeks, and 25 subjects belonging to the second group were treated with
imipramine twice daily (100 mg/day) for 6 weeks and then
amantadine was introduced (150 mg/day, twice daily) and administered jointly with
imipramine for the successive 6 weeks. Hamilton Depression Rating Scale (HDRS) was used to assess the efficacy of
antidepressant therapy.
Imipramine did not change the HDRS score after 3, 6 or 12 weeks of treatment when compared with the washout (before treatment). The addition of
amantadine to the classic
antidepressant reduced HDRS scores after 6-week joint treatment. Moreover, the obtained pharmacokinetic data indicated that
amantadine did not significantly influence the plasma concentration of
imipramine and its metabolite
desipramine in patients treated jointly with
imipramine and
amantadine, which suggests lack of a pharmacokinetic interaction. The obtained results indicate that joint
therapy with an
antidepressant and
amantadine may be effective in treatment-resistant
unipolar depression.