Add-on Cariprazine in Patients with Long-term Clozapine Treatment and Treatment Resistant Schizophrenia: Two Cases of Psychotic Deterioration and Pisa Syndrome

An increasing number of studies deal with medical options for treatment resistant schizophrenia. If no remission can be achieved with clozapine, a combination of antipsychotics can be considered. The combination of clozapine and cariprazine is rarely studied. Cariprazine is a partial agonist on dopamine D2 and D3 receptors and a pharmaceutically rational add-on to clozapine. Stimulating D3 receptors has been linked to improved cognition and mood, with negligible extrapyramidal side effects. We present two patients with long-term treatment resistant schizophrenia receiving cariprazine and clozapine. Whereas psychotic symptoms worsened, the patients developed extrapyramidal side effects with a Pisa syndrome. The syndrome remitted after discontinuation of cariprazine. Possible explanations by pharmacodynamic interactions and drug specific receptor profiles are discussed.