title: Effects of fluoxetine, indomethacine and placebo on 3 alpha, 5 alpha 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.
  
  
  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.
authors.affiliation: Department of Neuroscience, Tor Vergata University, IRCCS Santa Lucia, Rome, Italy. romeo@uniroma2.it
authors.forename: E
authors.initials: E
authors.lastname: Romeo
authors.forename: E
authors.initials: E
authors.lastname: Pompili
authors.forename: F
authors.initials: F
authors.lastname: di Michele
authors.forename: M
authors.initials: M
authors.lastname: Pace
authors.forename: R
authors.initials: R
authors.lastname: Rupprecht
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: A
authors.initials: A
authors.lastname: Pasinib
mesh_terms: 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
chemical_list: D000431:Ethanol; D005473:Fluoxetine; D007213:Indomethacin; D011280:Pregnanolone; D017367:Selective Serotonin Reuptake Inhibitors; D005680:gamma-Aminobutyric Acid