Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments

Abstract

The relationship between the ratio in plasma of tryptophan to competing amino acids, which indicates brain serotonin synthesis, and the clinical response in depressed patients to treatments that act by enhancing brain serotoninergic function has been studied. There was a significantly positive correlation between the pretreatment plasma tryptophan ratio and the final depression score in patients treated with L-tryptophan or amitriptyline, and a trend towards a positive correlation in patients treated with lithium plus L-tryptophan or clomipramine. Patients with a low plasma tryptophan ratio generally showed greater clinical improvement than patients with a high ratio. When the plasma tryptophan ratio and the ratio in plasma of tyrosine to competing amino acids were considered together there was also a significant relationship between clinical and biochemical findings in patients treated with imipramine. These studies strongly indicate that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression. Evidence has furthermore been presented which suggests that, rather than a low brain serotonin level per se, the hypofunction may be associated with disturbances in adaptive and regulatory mechanisms, e.g. postsynaptic serotonin receptors.