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-HT1A receptors. It also exhibits antagonist activity at 5-HT2A, 5-HT2B, 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-HT2C 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.
- Laszlovszky I, Barabássy Á, Németh G. Cariprazine, A broad-spectrum antipsychotic for the treatment of schizophrenia: pharmacology, efficacy, and safety. Advances in Therapy. 2021; 38: 3652-73.
- Reagila® (Cariprazine) Australian approved product information. Melbourne: Seqirus. Approved November 2020.
- Therapeutic Goods Administration. Australian Public Assessment Report for Cariprazine hydrochloride. Woden: TGA; 2021.