title: Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients.
abstract: Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder.
authors.affiliation: Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. bdg@helix.nih.gov
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
authors.forename: J
authors.initials: J
authors.lastname: Benjamin
authors.forename: J D
authors.initials: JD
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Keuler
authors.forename: S J
authors.initials: SJ
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Altemus
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001519:Behavior / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008711:Metergoline / Q000494:pharmacology*; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D008711:Metergoline; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors