Delayed obsessive compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients

Enhanced serotonergic transmission may underlie therapeutic effects of sero tonin reuptake inhibitors in obsessive-compulsive disorder. However, such t reatment may decrease serotonin receptor responsivity. We investigated whet her the serotonin antagonist metergoline would exacerbate or further improv e systems in fluoxetine-responsive patients. Pilot results suggested open m etergoline produced delayed symptom worsening in fluoxetine-treated patient s. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterward s. Ten unmedicated patients underwent the same procedures. Symptoms improve d 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 uncha nged. Metergoline had no similar delayed effects in unmedicated patients. M etergoline 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 obsessiv e-compulsive disorder.