Clomipramine in obsessive-compulsive disorder. Further evidence for a serotonergic mechanism of action.
Data from several previous studies link clomipramine's potent serotonergic effects to its clinical efficacy in reducing the symptoms of obsessive-compulsive disorder (OCD). To investigate this relationship further, we administered the serotonin (5-HT) receptor antagonist, metergoline, and placebo to ten patients with OCD in a crossover study carried out under double-blind, random-assignment conditions. In a previous study of untreated patients with OCD, we found no differences in the behavioral response to single-dose administration of metergoline or placebo. In the present study, patients with OCD receiving clomipramine hydrochloride on a long-term basis (with an average 40% lessening in OC symptoms) responded to a four-day period of administration of metergoline with significantly greater self- and observer-rated anxiety compared with the four-day placebo period. Obsessive-compulsive symptoms also tended to be greater during the metergoline phase, with significant drug-time interactions for both OC symptoms and anxiety peaking on day 4 of the metergoline phase. As anticipated, metergoline lowered plasma prolactin concentrations (providing evidence of physiologically significant 5-HT antagonism) but did not alter plasma clomipramine concentrations. These data further support the hypothesis that clomipramine's therapeutic behavioral effects in OCD are mediated via serotonergic mechanisms.
Benkelfat
C
C
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Murphy
D L
DL
Zohar
J
J
Hill
J L
JL
Grover
G
G
Insel
T R
TR
D000328:Adult; D000339:Affect / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D013997:Time Factors
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008711:Metergoline; D012701:Serotonin; D002997:Clomipramine