5-HT uptake inhibitors and tricyclic antidepressants: relation between tryptophan availability and clinical response in depressed patients.

The amount of tryptophan (Trp) available for transport from plasma into the brain was estimated in patients with major depression before treatment for 4 weeks with a 5-HT potentiating tricyclic antidepressant (TCA), amitriptyline (n = 21) or clomipramine (n = 17), or a selective 5-HT uptake inhibitor, citalopram (n = 14) or paroxetine (n = 27). The ratio in plasma of Trp to the sum of the other large neutral amino acids (LNAA) was significantly inversely correlated with improvement on TCA, and patients with ratio Trp/LNAA below the mean improved significantly more than patients with a higher ratio but with comparable serum steady-state drug levels. The Trp concentration was a bit stronger inversely correlated with improvement on 5-HT uptake inhibitors than the ratio Trp/LNAA, and patients with Trp level below the mean improved significantly more than those with a higher level but with comparable serum steady-state drug levels. Plasma amino acid variables may be a useful tool for increasing the efficacy of antidepressant treatment.