The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron® was evaluated. About 40 in-patients were investigated by a randomised double-blind placebo-controlled study during 4 weeks. Plasma levels of 20 amino acids and measures of depression, suicidal behaviour and aggression were surveyed on admission and after a 4 weeks’ therapy with Remeron® plus an individualized amino acid mixture or placebo. The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism. Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group. The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant. Furthermore, lacking side effects of the amino acids resulting also in a better patient compliance may improve the benefit/risk ratio.