Obsessive-compulsive disorder and serotonin: is there a connection?
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.
T R
TR
Insel
E A
EA
Mueller
I
I
Alterman
M
M
Linnoila
D L
DL
Murphy
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003891:Desipramine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015031:Zimeldine / Q000627:therapeutic use*
D012701:Serotonin; D015031:Zimeldine; D006897:Hydroxyindoleacetic Acid; D003891:Desipramine