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. Method: 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.

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