A double-blind, placebo controlled study that was published in Acta Psychiatrica Scandinavica (1979;59:395-414) compared three different treatment approaches in 25 severely depressed individuals aged 18-60. One group was given a combination of nicotinamide and tryptophan, one group was given imipramine (a tricyclic antidepressant medication) and a third group was given a combination of imipramine with the tryptophan and nicotinamide.

The researchers looked at the blood level of tryptophan and compared it to the response to the therapy. In the group given the tryptophan and the nicotinamide, a favorable response to therapy correlated with an increase of tryptophan in the blood. In the group given the drug and the supplements, there was a negative correlation between tryptophan levels and response to the therapy—suggesting that the tryptophan levels were too high. The researchers concluded that supplementation with tryptophan and nicotinamide may be as effective as the drug therapy. Also, at low doses, the supplementation may make the drug therapy more effective.