Antipsychotic medications can cause Obsessive Compulsive Disorder (OCD). This may be more common with clozapine because of its potent serotonin receptor antagonism. There are multiple approaches for managing OCD symptoms caused by clozapine treatment. OCD may be related to clozapine dose or blood level. One can check a clozapine level, and consider a slow reduction in dosage, to see if psychosis is still managed at a lower level and OCD symptoms improve. In addition, there is evidence for the use of serotonin reuptake inhibitors (SSRIs) if the patient has no history of mania. When prescribing SSRIs, one needs to consider that SSRIs can, to varying degrees, raise clozapine levels through P450 interactions. For some SSRIs, these increases can be substantial, even 5 or 10 fold, though interactions are unpredictable. SSRIs known to have very strong P450 interactions, such as fluvoxamine, should be avoided or used very carefully. Clomipramine is associated with side effects and generally avoided. Strong inhibitors of P450 (e.g. fluoxetine, paroxetine) can increase clozapine levels about 2-fold. SSRIs with fewer side effects and lower P450 interactions, such as escitalopram, citalopram, or sertraline, are preferable. Clozapine dosages should be adjusted as needed and levels closely monitored. Evidence based behavioral therapies for OCD can also be considered.