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Obsessive—Compulsive Disorder as a 5-HT Subsystem-Related Behavioural Disorder

Published online by Cambridge University Press:  06 August 2018

D. L. Murphy ,
J. Zohar ,
C. Benkelfat ,
M. T. Pato ,
T. A. Pigott  and
T. R. Insel
D. L. Murphy*
Affiliation:
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
J. Zohar
Affiliation:
Beer-Sheva Mental Health Centre, Beer-Sheva, Israel
C. Benkelfat
Affiliation:
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
M. T. Pato
Affiliation:
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
T. A. Pigott
Affiliation:
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
T. R. Insel
Affiliation:
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
*
∗Correspondence
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Extract

Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semi-selective serotonin uptake inhibitor, clomipramine. More recent studies directly comparing clomipramine with non-selective or norepinephrine-selective uptake inhibitors, such as desipramine or nortriptyline, as well as studies with new, more selective serotonin uptake inhibitors, including fluvoxamine and fluoxetine, have supported that hypothesis. Clomipramine's antiobsessional effect has been augmented with the serotonin precursor, L-tryptophan, or with lithium, which has prominent serotonergic effects. Patients whose OCD symptoms improved on clomipramine worsened when the drug was discontinued (regardless of duration of therapy) and improved when clomipramine was reinstituted. OCD symptoms also worsened when metergoline, a 5-HT antagonist, was given to patients who had improved with clomipramine. Metergoline given alone had no effect. Administration of m-chlorophenylpiperazine (m-CPP), a 5-HT receptor agonist, to untreated OCD patients increased their anxiety, depression, and dysphoria, and exacerbated their OC symptoms. After 4 months of clomipramine therapy, m-CPP failed to produce the same behavioural effects, suggesting an alteration of a 5-HT subsystem (possibly downregulation of some 5-HT receptors). The data reviewed suggest an important role for an abnormal brain 5-HT subsystem in patients with OCD.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 155 , Issue S8: SEROTONIN IN BEHAVIOURAL DISORDERS , December 1989 , pp. 15 - 24
Copyright
Copyright © Royal College of Psychiatrists, 1989 

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