Obsessive-compulsive disorder and serotonin: is there a connection?

Biol Psychiatry. 1985 Nov;20(11):1174-88. doi: 10.1016/0006-3223(85)90176-3.


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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Blood Platelets / metabolism
  • Central Nervous System / metabolism*
  • Clinical Trials as Topic
  • Desipramine / therapeutic use*
  • Female
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Male
  • Obsessive-Compulsive Disorder / drug therapy
  • Obsessive-Compulsive Disorder / metabolism*
  • Serotonin / metabolism*
  • Zimeldine / therapeutic use*


  • Serotonin
  • Zimeldine
  • Hydroxyindoleacetic Acid
  • Desipramine