Relationship between clozapine dose and severity of obsessive-compulsive symptoms

Evidence supports the fact that clozapine can induce stressful obsessive-compulsive symptoms (OCS). Although clozapine's robust inhibition of serotonergic neurotransmission is believed to be a key mechanism underlying clozapine-induced OCS, the exact mechanism(s) are not fully understood. Intuitively, it is reasonable to believe that the dose of clozapine is likely related to emergent OCS severity. However, there is conflicting evidence where both positive and inverse relationships have been demonstrated between clozapine dose and emergent OCS severity. Upon examination of clozapine's receptor profile, in particular its affinity for 5-HT_2A and D₂ receptors, we hypothesize that there is a biphasic relationship between clozapine dose and emergent OCS severity. We present here a preliminary analysis of published cases in the literature to support our hypothesis.