Antiobsessional Effect of Risperidone Add-On Treatment in Serotonin Reuptake Inhibitor–Refractory Obsessive-Compulsive Disorder May Be Dose-Dependent

In their recent article, McDougle et al¹ concluded that patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy may respond to a mean ± SD low dose of risperidone (2.2 ± 0.7 mg) added to SRI treatment. However, the observed relationship between low doses of risperidone and its antiobsessional effect needs further evaluation.

Positron emission tomography studies have shown that risperidone, even at low doses (≤2 mg), exhibits a high occupancy of serotonin, (5-HT₂) receptors (≥80%), while a moderate dose (2-6 mg) is required to induce 66% to 80% of dopamine type 2 (D₂) occupancy.² Dopamine type 2 antagonists such as pimozide and haloperidol seem to augment the efficacy of SRIs in refractory OCD with tics and schizotypal disorder,^3- 4 suggesting that dopamine D₂ antagonism in combination with serotonin reuptake inhibition may enhance their therapeutic efficacy for OCD. Taking into account that D₂ antagonism may have antiobsessional effects, and that risperidone induces dopamine D₂ antagonism in a dose-dependent fashion, it can be assumed that upward titration of risperidone may be required to alleviate obsessive-compulsive (OC) symptoms in refractory OCD. Accordingly, Saxena et al⁵ found a dose-dependent response rate in patients with OCD. An average daily dose of 2.75 mg of risperidone was associated with a high response rate (23.8%), compared with an average daily dose of 1.25 mg that achieved improvement in only 12.5% of patients with OCD. Similarly, we have observed in a case series an inverse association between the dosage of atypical antipsychotics (risperidone, olanzapine) and OC symptoms.⁶