Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs.
BACKGROUND
Previous reports suggest that some atypical antipsychotics may have obsessogenic as well as antiobsessional effects. Given their higher affinity for serotonin 5HT2 receptors than dopamine D2 receptors, it has been speculated that atypical antipsychotics may induce obsessive-compulsive (OC) symptoms, even at low doses, due to high 5HT2 antagonism, whereas improvement in OC symptoms is thought to occur only at high doses due to high D2 antagonism.


METHODS
In this open case series, the dose-response relationship of atypical antipsychotic augmentation in the treatment of obsessive compulsive disorder (OCD), and the dose-severity relationship in atypical anti psychotic-induced OC symptoms were examined. Three patients were identified who had either refractory OCD or OC symptoms following administration of atypical antipsychotics such as olanzapine and risperidone.


RESULTS
Case 1: A linear dose-response relationship between increasing doses of olanzapine and improvement in OC symptoms was observed in an OCD patient resistant to 5-HT reuptake inhibitors. 2: OC symptoms induced by low doses of risperidone (1 mg) were reversed by increasing the doses of risperidone (3 mg) in a bipolar disorder patient suggesting an inverse dose-severity relationship. 3: No inverse dose-severity relationship was noted between olanzapine induced OC symptoms and its dosage in an asymptomatic OCD patient. Tretment-emergence OC symptoms responded to increasing the doses of maintanance clomipramine treatment.


CONCLUSIONS
Controlled studies are needed to investigate the dose-response or dose-severity relationships between OCD and atypical antipsychotics.
Ramasubbu
R
R
Department of Psychiatry, University of Ottawa, Royal Ottawa Hospital, Ontario, Canada. rramasub@rohcg.on.ca
Ravindran
A
A
Lapierre
Y
Y
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines; D002997:Clomipramine / Q000008:administration & dosage; D018492:Dopamine Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000188:drug therapy*; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D002997:Clomipramine; D018492:Dopamine Antagonists; D000077152:Olanzapine; D010890:Pirenzepine; D018967:Risperidone; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors