Plasma ratio tryptophan/neutral amino acids in relation to clinical response to paroxetine and clomipramine in patients with major depression.

The pretreatment plasma ratio of tryptophan (Trp) to other large neutral amino acids (LNAA), thought to reflect brain serotonin formation, was determined in 44 inpatients with major depression, who were subsequently treated double-blind on a fixed-dose schedule for 4 weeks with the selective serotonin uptake inhibitor paroxetine (n = 27) or clomipramine (n = 17). The study took place at four clinical centers. Endogenous and non-endogenous depressives were comparable with respect to the ratio Trp/LNAA and clinical improvement and were therefore analyzed together. The clomipramine group showed a significant inverse correlation between ratio Trp/LNAA and improvement, and patients with a ratio Trp/LNAA below the mean showed a trend towards greater improvement than patients with a higher ratio but with comparable serum drug levels. The improvement in the paroxetine group was significantly inversely correlated with the Trp concentration but not with the ratio Trp/LNAA. The findings accord with previous trials of various antidepressant treatments, in which about 25% of the variance in therapeutic response associates with pretreatment plasma amino acid profiles.