Depression during methadone withdrawal: No role for β-phenylethylamine

Abstract

An atypical depression, resembling β-phenylethylamine (PEA) deficiency states, frequently complicates methadone withdrawal. We undertook a study of 24-h urinary free PEA excretion in steady-dosed and withdrawing methadone patients, hypothesizing that abstinent patients would excrete less PEA than controls and that methadone would show a dose-dependent effect on PEA turnover. As hepatic dysfunction, frequent in methadone patients, might affect PEA turnover, we also evaluated liver chemistries, [ 13C]aminopyrine excretion, 2-hydroxylation of estradiol, and ‘blind’, global severity ratings in each subject. PEA excretion did not significantly differ between eight fully detoxified methadone patients (median 4.76 μg/24 h) and seven normal controls (median 5.80 μg/24 h). Moreover, PEA excretion bore no relation to methadone dosage among 24 steadydosed subjects. PEA excretion in seven withdrawing subjects each receiving 4–8 different doses of methadone similarly showed no relation to dose. Despite significant liver disease, several measures of impairment did not correlate with PEA excretion. These findings argue against a role for PEA deficiency in withdrawal depression.