Effects of Fluoxetine, Indomethacine and Placebo on 3α, 5α Tetrahydroprogesterone (THP) Plasma Levels in Uncomplicated Alcohol Withdrawal

Abstract

OBJECTIVE: The purpose of this study was to investigate the effects of fluoxetine (F) and indomethacine (I), two drugs that regulate the synthesis of the GABAergic neurosteroid 3 alpha, 5 alpha tetrahydroprogesterone (allopregnanolone, THP) on THP plasma levels and on symptoms of anxiety and depression in alcoholics during ethanol withdrawal. METHOD: Patients who met DSM-IV criteria for alcohol abuse were randomly assigned to treatment with F (40 mg/day) plus misoprostol (M) (500 mg/day) or I (100 mg/day) plus M or placebo (PL) plus M. Patients were rated with the Hamilton Anxiety (14-HAS) and Depression (17-HDS) scales on days 1, 5, 7, 15 and 28 of ethanol withdrawal and with a Visual Analogue Scale for Depression (VASD) and a Visual Analogue Scale for Anxiety (VASA) on days 1, 2, 4, 5, 7, 15 and 28 of withdrawal. On the same days a plasma sample was collected to measure the concentrations of THP by means of a very sensitive gas chromatographic mass spectrometric method. RESULTS: During withdrawal at days 1, 2, 4 and 5, THP plasma values were lower and symptoms of anxiety and depression were significantly higher compared to the late withdrawal phase at days 15 and 28. In the F or I treatment, the depression and anxiety score, measured by VASD and VASA, decreased significantly at day 5-7 whereas THP plasma levels significantly increased compared to PL condition CONCLUSIONS: Treatment of alcohol withdrawal either with F or I reduced the extent of anxiety and depression and normalised THP plasma levels that were decreased during withdrawal.