Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine.
To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).
Goodman
W K
WK
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Price
L H
LH
Delgado
P L
PL
Palumbo
J
J
Krystal
J H
JH
Nagy
L M
LM
Rasmussen
S A
SA
Heninger
G R
GR
Charney
D S
DS
D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy / Q000523:psychology; D001479:Basal Ganglia / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D003891:Desipramine / Q000627:therapeutic use; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D016666:Fluvoxamine; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D010200:Panic; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000627:therapeutic use*
D010091:Oximes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D016666:Fluvoxamine; D003891:Desipramine; D004298:Dopamine