Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults.

Oct 8, 2020

Contributor: Amber Edinoff,Miriam T Ruoff,Yahya T Ghaffar,Arthur Rezayev,Devanshi Jani,Adam M Kaye,Elyse M Cornett,Alan D Kaye,Omar Viswanath,Ivan Urits

Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults.

Antipsychotics are the standard of care when it comes to the treatment of Schizophrenia, and they are often used in Bipolar as well. Their use can come with adverse effects such as extrapyramidal movements, metabolic complications as well as cardiovascular complications such as a prolonged QT interval. Treatment for these side effects ranges from the treatment of the complications up to the cessation of the medication, which could come at the expense of the user’s stability. Both schizophrenia and bipolar disorder have an increased risk of suicide and increased morbidity. The purpose of this review presents the background, evidence, and indications for the use of the new second-generation antipsychotic Cariprazine, which has a primary function as a D3 and D2 partial agonist, with higher selectivity for the D3 receptor type.

Schizophrenia is currently teated by dopamine antagonists and/or 5HT modulators, each with their own set of side effects. Bipolar disorder is mostly treated with mood stabilizers. Studies looking at the efficacy and safety of cariprazine have shown in two phase II trials and phase III trials the decrease in PANSS scores in schizophrenia. The most common adverse effects were akathisia, insomnia, constipation, and other extrapyramidal side effects. A unique side effect of Cariprazine caused bilateral cataract and cystic degeneration of the retina in the dog following daily oral administration for 13 weeks and/or 1 year and retinal degeneration in rats following daily oral administration for 2 years. Another study showed that cariprazine had significant efficacy in preventing relapse in patients with schizophrenia.

The time to the loss of sustained remission was significantly longer (P = .0020) for cariprazine compared to placebo (hazard ratio = 0.51) during the double-blind treatment. 60.5% of patients treated with cariprazine and 34.9% of patients treated with placebo sustained remission through the final visit (odds ratio [OR] = 2.85; P = .0012; number needed to treat [NNT] = 4. Another Phase IIIb study looked at negative symptoms and used the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and it found that the use of cariprazine, from baseline to week 26, led to a greater least-squares mean change in PANSS-FSNS than did risperidone. Another study looked at the quality of life years with the treatment of cariprazine and showed those treated with cariprazine had superior quality of life compared to those treated with risperidone. In terms of bipolar disorder, it showed a decrease in depressive symptoms as measured by decreased MADRs scores with a dose of 3.0mg/day.

A phase II study looked at the use of cariprazine in mania or mix states and showed cariprazine significantly decreased YMRS scores compared to placebo, least-square mean difference of -6.1 (p < 0.001). The metabolic parameters demonstrated comparable changes except for fasting glucose in which cariprazine was associated with elevations in glucose levels compared to placebo (p < 0.05). Another phase III study showed significant differences in YMRS total score mean change between cariprazine versus placebo-treated group. Changes in metabolic profiles in all mentioned studies were minimal.

Cariprazine, in recent studies, has shown some promise in being able to treat both bipolar disorder in manic, depressed, and mixed states as well as schizophrenia. Side effects noted as adverse events in these studies are similar in profile to the medications that were developed in the past. With better relapse prevention, cariprazine could be a reasonable alternative clozapine.

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Amber Edinoff

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Miriam T Ruoff

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Yahya T Ghaffar

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Arthur Rezayev

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Devanshi Jani

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Adam M Kaye

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Elyse M Cornett

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Alan D Kaye

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Omar Viswanath

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

Ivan Urits

Edinoff, MD, Jani, MD, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. Ruoff, BA, Ghaffar, BS, Rezayev, BS, Louisiana State University Shreveport School of Medicine. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Kaye, MD, PhD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ. Urits, MD, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.

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Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults.

Contributor: Amber Edinoff,Miriam T Ruoff,Yahya T Ghaffar,Arthur Rezayev,Devanshi Jani,Adam M Kaye,Elyse M Cornett,Alan D Kaye,Omar Viswanath,Ivan Urits

Author

About The Expert

References