BIOL PSYCHIATRY 1991 ~ : ~ Longitudinal Effect of Amitriptyline and Fluoxetine Treatment on Plasma Phenylacetic Acid Concentrations in Depression Bruce A. Davis, Alan A. Boulton, Peter H. Yu, David A. Durden, David L. Keegan, Rudradeo C. Bowen, Stella Blackshaw, Carl D'Arcy, A. J. Remillard, N. Dayal, Satish Shrikhande, S. Saleh, G~0riel H. Stegeman, and I. Alick Paterson Unconjugated (U-PA~ ;, conjugated (C-PAA), ~ total phenylacetic acid (T-PAA) con- centrations in blood plasma and monoamine oxicL~.se (MAO) activity in platelets towards pheny!ethylamine (PE) were determined in 40 drug-free, depressed patients (23 melan- cholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all de- pressed patients or between melancholic and nonmelancholic depressed patients. Treat- ment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentra- tions. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment ;imes, however, plasma PAA concentrations and psychiatric rating scores were not sign~cantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores. Introduction Several investigators have suggested over the last few years, that a reduced urinary excretion of total phenylacetic acid (T-PAA) may be a useful marker for depression (Sabelli et al 1983a, 1983b, 1986, 1990, DeLisi et al 1984; Gusovsky et al 1984, Gonzalez- Sastre et al 1988). Others, however, have failed to confirm this reduction (Sandier et a] From the Neuropsychiatric Research Unit (BAD, AAB, PHY, DAD, GHS, lAP), Departments of Psychiatry (DLK, RCB, SB. CD) a~ld Pharmacy, University of Saskatchewan, Saskatoon, Saskatchewan (AJR) and the Mental Health Services, Regina, Saskatchewan (ND,SS), Canada. Address reprint requests to Dr. Bruce A. Davis, Neuropsychiatric Research Unit, A! 14 Medical Research Building, Saskatoon, Saskatchewan, Canada S7N 0W0. Received August 22, 1990; revised April 8, 1991. © 1991 Society of Biological Psychiatry 0006-3223/91/$03.50