Cariprazine for schizophrenia: The benefits of D3-preferring antipsychotics
14 Apr 2025
Dr Roger S McIntyre delivering his lecture.Dr Roger S McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, shared his insights on cariprazine as treatment for schizophrenia at the “Mechanistically informed therapeutics: A focus on the D3 receptor mechanistic and clinical translation” symposium held at the EDSA Shangri-La Hotel on 22 January 2025.
Schizophrenia is a mental health condition which is treated by blocking dopamine receptors present in dopaminergic pathways, especially those in the mesolimbic and mesocortical pathways.1–3 Existing antipsychotics are generally nonselective D2 antagonists which can disrupt receptors in the nigrostriatal and tuberoinfundibular pathways, resulting in adverse side effects.2–4
The D3 receptor is an alternative target for new antipsychotics. Compared with D2 receptors, D3 receptors have a higher affinity for dopamine and are found mainly in limbic areas, as well as the hypothalamus and ventral tegmental area, where the receptors modulate cognition and motivation.5 Due to the distribution of D3 receptors, the use of D3-preferring antipsychotics could spare patients from side effects associated with D2 antagonists.
Cariprazine (Reagila) is a third generation antipsychotic and partial agonist for D2 and D3 receptors. Compared with other third generation antipsychotics, cariprazine has the highest affinity for D3 receptors.6 Two active metabolites are derived from cariprazine after administration: desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). DDCAR has a half-life of 1 to 3 weeks, ensuring sustained action.7,8
Cariprazine is a new addition to the roster of available antipsychotics in the Philippines providing both healthcare professionals and patients with new solutions to challenges inherent to the treatment of schizophrenia.
The recommended dosage of cariprazine for patients with schizophrenia is 3 to 6 mg per day.1,9 In a phase 3 study where cariprazine was administered throughout the course of 6 weeks to patients with schizophrenia, results showed patients who received 3 to 6 mg per day achieved improved Positive and Negative Syndrome Scale scores compared with patients who received placebo (-22.8 vs -16.0; 95% CI, -11.3 to -2.4; p=0.003).1
Long-term use of cariprazine reduces the chances of relapse in patients with schizophrenia compared with placebo.10 Results of a clinical trial showed relapse occurring in only 24.8% of patients treated with cariprazine (vs placebo, 47.5%; HR, 0.45; 95% CI, 0.28−0.73; p<0.001).10 Though continuous use of antipsychotics is associated with psychotropic drug-related weight gain, cariprazine poses a low risk of weight gain and should be suitable for extended use.11
The benefits of cariprazine extend beyond schizophrenia: patients affected by bipolar mania with or without mixed features and bipolar depression with or without mixed features see improved Young Manic Rating Scale and Montgomery-Åsberg Depression Rating Scale scores after administration of cariprazine.12,13
Healthcare professionals should consider cariprazine when prescribing an antipsychotic. The benefits of using cariprazine as treatment for schizophrenia, bipolar disorders and other mental health conditions, as well as the absence of side effects stemming from the use of D2 antagonists, make it a promising option for patients with schizophrenia.
Dr Roger S McIntyre at the end of his lecture, answering questions from the audience.
References: 1. Kane JM, et al. J Clin Psychopharmacol 2015;35:367-373. 2. Stępnicki P, et al. Molecules 2018;23:2087. 3. Scarff JR. Ther Adv Psychopharmacol 2017;7:237-239. 4. Sykes DA, et al. Nat Commun 2017;8:763. 5. Stahl SM. CNS Spectr 2017;22:305-311. 6. Stahl SM. CNS Spectr 2017;22:375-384. 7. Nakamura T, et al. Drug Des Devel Ther 2016;10:327-338. 8. Periclou A, et al. Eur J Drug Metab Pharmacokinet 2021;46:53-69. 9. Reagila® (cariprazine) [product insert]. Budapest, Hungary: Gedeon Richter Plc.; 2023. 10. Durgam S, et al. Schizophr Res 2016;176:264-271. 11. McIntyre RS, et al. Am J Psychiatry 2024;181:26-38. 12. McIntyre RS, et al. J Affect Disord 2019;257:600-606. 13. McIntyre RS, et al. CNS Spectr 2020;25:502-510.
APH-CARI-04-25-00005
Schizophrenia is a mental health condition which is treated by blocking dopamine receptors present in dopaminergic pathways, especially those in the mesolimbic and mesocortical pathways.1–3 Existing antipsychotics are generally nonselective D2 antagonists which can disrupt receptors in the nigrostriatal and tuberoinfundibular pathways, resulting in adverse side effects.2–4
The D3 receptor is an alternative target for new antipsychotics. Compared with D2 receptors, D3 receptors have a higher affinity for dopamine and are found mainly in limbic areas, as well as the hypothalamus and ventral tegmental area, where the receptors modulate cognition and motivation.5 Due to the distribution of D3 receptors, the use of D3-preferring antipsychotics could spare patients from side effects associated with D2 antagonists.
Cariprazine (Reagila) is a third generation antipsychotic and partial agonist for D2 and D3 receptors. Compared with other third generation antipsychotics, cariprazine has the highest affinity for D3 receptors.6 Two active metabolites are derived from cariprazine after administration: desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). DDCAR has a half-life of 1 to 3 weeks, ensuring sustained action.7,8
Cariprazine is a new addition to the roster of available antipsychotics in the Philippines providing both healthcare professionals and patients with new solutions to challenges inherent to the treatment of schizophrenia.
The recommended dosage of cariprazine for patients with schizophrenia is 3 to 6 mg per day.1,9 In a phase 3 study where cariprazine was administered throughout the course of 6 weeks to patients with schizophrenia, results showed patients who received 3 to 6 mg per day achieved improved Positive and Negative Syndrome Scale scores compared with patients who received placebo (-22.8 vs -16.0; 95% CI, -11.3 to -2.4; p=0.003).1
Long-term use of cariprazine reduces the chances of relapse in patients with schizophrenia compared with placebo.10 Results of a clinical trial showed relapse occurring in only 24.8% of patients treated with cariprazine (vs placebo, 47.5%; HR, 0.45; 95% CI, 0.28−0.73; p<0.001).10 Though continuous use of antipsychotics is associated with psychotropic drug-related weight gain, cariprazine poses a low risk of weight gain and should be suitable for extended use.11
The benefits of cariprazine extend beyond schizophrenia: patients affected by bipolar mania with or without mixed features and bipolar depression with or without mixed features see improved Young Manic Rating Scale and Montgomery-Åsberg Depression Rating Scale scores after administration of cariprazine.12,13
Healthcare professionals should consider cariprazine when prescribing an antipsychotic. The benefits of using cariprazine as treatment for schizophrenia, bipolar disorders and other mental health conditions, as well as the absence of side effects stemming from the use of D2 antagonists, make it a promising option for patients with schizophrenia.
Dr Roger S McIntyre at the end of his lecture, answering questions from the audience.References: 1. Kane JM, et al. J Clin Psychopharmacol 2015;35:367-373. 2. Stępnicki P, et al. Molecules 2018;23:2087. 3. Scarff JR. Ther Adv Psychopharmacol 2017;7:237-239. 4. Sykes DA, et al. Nat Commun 2017;8:763. 5. Stahl SM. CNS Spectr 2017;22:305-311. 6. Stahl SM. CNS Spectr 2017;22:375-384. 7. Nakamura T, et al. Drug Des Devel Ther 2016;10:327-338. 8. Periclou A, et al. Eur J Drug Metab Pharmacokinet 2021;46:53-69. 9. Reagila® (cariprazine) [product insert]. Budapest, Hungary: Gedeon Richter Plc.; 2023. 10. Durgam S, et al. Schizophr Res 2016;176:264-271. 11. McIntyre RS, et al. Am J Psychiatry 2024;181:26-38. 12. McIntyre RS, et al. J Affect Disord 2019;257:600-606. 13. McIntyre RS, et al. CNS Spectr 2020;25:502-510.
APH-CARI-04-25-00005