Cariprazine on the Pharmaceutical Benefits Scheme

Cariprazine is a new antipsychotic listed on the Pharmaceutical Benefits Scheme (PBS) for the treatment of schizophrenia. Cariprazine is an atypical agent with partial agonist activity at dopamine D₂ and D₃ receptors and 5-HT_1A receptors. It also exhibits antagonist activity at 5-HT_2A, 5-HT_2B, and histamine H₁ receptors.

While atypical antipsychotics have a better side effect profile than typical agents, they are not always effective in treating the negative symptoms of schizophrenia. The dopamine D₃ receptor has emerged as a possible target for negative symptoms due to their localisation in regions of the brain controlling reward, emotion, and motivation. Cariprazine has a much higher affinity for D₃ receptors than D₂ receptors. A randomised, double-blind clinical trial demonstrated that cariprazine was superior to risperidone for the treatment of negative symptoms.

The risk of cardiovascular and metabolic adverse effects may be lower with cariprazine compared to other atypical antipsychotics due to a lower affinity for 5-HT_2C and adrenergic α₁ receptors. The most common adverse effects reported are akathisia and parkinsonism.

Metabolism of cariprazine and its major active metabolites predominantly occurs through the cytochrome P450 system, CYP3A4 in particular. Coadministration with strong and moderate inhibitors or inducers of CYP3A4 is contraindicated. Patients should also be advised to avoid consuming grapefruit juice while taking cariprazine.