Tryptophan and tyrosine ratios to neutral amino acids in endogenous depression: Relation to antidepressant response to amitriptyline and lithium + L-tryptophan

Abstract

The plasma ratios of tryptophan and tyrosine to those amino acids that compete with them during transport across the blood-brain barrier have been determined in depressed patients before and after treatment for four weeks with amitriptyline or lithium + l-tryptophan. There was no relation between the absolute plasma concentrations of free or total tryptophan or tyrosine and the clinical response to amitriptyline. There was also no relation between pre-treatment ratio of plasma tyrosine to competing amino acids and response to amitriptyline, but depressives with subnormal tryptophan ratio improved significantly more than patients with supernormal tryptophan ratio with comparable serum drug levels. The therapeutic response to lithium + l-tryptophan was predicted neither by the absolute plasma concentrations of free or total tryptophan or tyrosine nor by the tyrosine ratio, but there was also a trend towards greater improvement in patients with subnormal compared with supernormal tryptophan ratio. The results suggest that the pre-treatment plasma ratio of tryptophan to competing amino acids is a useful predictor of clinical response to amitriptyline. The possible mode of action of amitriptyline and lithium + l-tryptophan is briefly discussed.