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Abstract
Reports of the antiobsessional efficacy of clomipramine have led to a “serotonin hypothesis”
of obsessive-compulsive disorder (OCD). To test this hypothesis, 16 outpatients with
DSM-III OCD were studied using several measures of serotonergic function. Platelet
3H-imipramine binding and serotonin uptake were not significantly different between
the OCD patients and a normal, age-matched control group. The level of the metabolite
5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) was significantly
higher in a small cohort of obsessionals compared with healthy volunteers, possibly
reflecting increased brain serotonin turnover. In a direct test of the role of serotonin
uptake in clomipramine's antiobsessional effects, the serotonin uptake inhibitor zimelidine
was compared with the noradrenergic uptake inhibitor desipramine in a double-blind,
controlled study. Zimelidine reduced CSF 5-HIAA, but was clinically ineffective in
this group. Desipramine had weak but significant clinical effects. Nonresponders to
zimelidine or desipramine improved significantly during a subsequent double blind
trial of clomipramine. These findings demonstrate that pharmacological blockade of
serotonin reuptake alone is not sufficient for an antiobsessional response.
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Article info
Publication history
Received in revised form:
June 19,
1985
Received:
March 21,
1985
Identification
Copyright
© 1985 Published by Elsevier Inc.