Effects of fluoxetine, indomethacine and placebo on 3 alpha, 5 alpha tetrahydroprogesterone (THP) plasma levels in uncomplicated alcohol withdrawal.
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.


METHODS
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.
Romeo
E
E
Department of Neuroscience, Tor Vergata University, IRCCS Santa Lucia, Rome, Italy. romeo@uniroma2.it
Pompili
E
E
di Michele
F
F
Pace
M
M
Rupprecht
R
R
Bernardi
G
G
Pasinib
A
A
D000328:Adult; D003865:Major Depressive Disorder / Q000175:diagnosis; D039721:Diagnostic and Statistical Manual of Mental Disorders; D000431:Ethanol / Q000009:adverse effects*; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D011280:Pregnanolone / Q000097:blood / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000431:Ethanol; D005473:Fluoxetine; D007213:Indomethacin; D011280:Pregnanolone; D017367:Selective Serotonin Reuptake Inhibitors; D005680:gamma-Aminobutyric Acid