Cariprazine for Bipolar Disorder

Overseen By Martin Lan, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: New York State Psychiatric Institute

Must be taking: Antidepressants, Antipsychotics

Must not be taking: Fluoxetine, Strong CYP3A4 inducers

Disqualifiers: Schizoaffective, Psychotic depression, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will use cariprazine (Vraylar) to treat individuals with bipolar depression who are not currently on medication. Researchers will use brain scans to understand how the medication affects the brain. The goal is to improve treatment options for those who do not respond well to current medications.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with cariprazine or if you have not achieved partial remission with your current antidepressant or antipsychotic. However, you can continue taking mood stabilizers if the dose hasn't changed recently, and benzodiazepines and hypnotics are allowed. If you're on stimulant medications, you'll need to stop them during the study.

What data supports the effectiveness of the drug Cariprazine for treating bipolar disorder?

Cariprazine is effective for treating acute manic and mixed episodes in bipolar disorder, with doses of 3-12 mg/day, and shows benefits for bipolar depression at doses of 1.5-3 mg/day. It is generally well-tolerated, with common side effects like restlessness and nausea, and does not have significant metabolic concerns. ^{1 2 3 4 5}

Is cariprazine safe for humans?

Cariprazine, also known as Vraylar, is generally considered safe for humans and has been approved for treating schizophrenia and bipolar disorder. Studies have evaluated its safety and tolerability, showing it is well-tolerated in patients with bipolar disorder, though like all medications, it may have side effects. ^{1 3 6 7 8}

How is the drug Cariprazine unique in treating bipolar disorder?

Cariprazine is unique because it is an oral antipsychotic that targets dopamine D3 receptors more than D2 receptors, which may help with both manic and depressive episodes in bipolar disorder. It is generally well-tolerated and does not have significant metabolic side effects, making it a novel option compared to other treatments. ^{1 2 3 5 9}

Research Team

Martin Lan, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults aged 18-60 with bipolar I disorder and current major depressive episode, scoring at least 16 on the Hamilton Depression Rating Scale. They must be willing to use birth control if applicable, tolerate medication washout, and can continue certain mood stabilizers. Excluded are those with head trauma affecting cognition, metal implants incompatible with MRI, excessive radiation exposure, claustrophobia preventing scans, weight over 350 lbs., failed or intolerable past cariprazine treatment.

Inclusion Criteria

I have bipolar I disorder and am currently experiencing a major depressive episode.

I am experiencing severe depression, as measured by a specific depression scale.

I understand the study and have given my consent.

Exclusion Criteria

Participant meets DSM5 criteria for manic episode at the time of screening, or has YMRS > 12

Metal implants, cardiac pacemaker, metal prostheses, metal orthodontic appliances or shrapnel in the body unless there is confirmation that the substance is MRI compatible

I've gotten worse in the past when stopping any of my current medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cariprazine (Vraylar) for six weeks with brain imaging using PET scans before and during treatment

6 weeks

3 visits (in-person) for PET scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cariprazine

Trial Overview The study tests cariprazine (Vraylar) in treating bipolar depression while examining its effect on D3 dopamine receptors using PET brain imaging. Participants will undergo a medication regimen followed by brain scans before and during treatment to understand how the drug interacts with specific brain receptors.

Participant Groups

Group I: Cariprazine 3 mg Experimental Treatment 1 Intervention

Participants will receive 3 mg daily of cariprazine (Vraylar) for six weeks

Group II: Cariprazine 1.5 mg Experimental Treatment 1 Intervention

Participants will receive 1.5 mg daily of cariprazine (Vraylar) for six weeks

Cariprazine is already approved in United States for the following indications:

Approved in United States as Vraylar for:

• Schizophrenia
• Acute manic or mixed episodes associated with bipolar I disorder
• Depressive episodes associated with bipolar I disorder (bipolar depression)
• Adjunctive treatment with an antidepressant therapy (ADT) for major depressive disorder (MDD)

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Findings from Research

Cariprazine (Vraylar) is an atypical antipsychotic that acts as a partial agonist at dopamine D3 and D2 receptors, with a preference for D3, and also affects serotonin 5-HT1A receptors, which contributes to its therapeutic effects.

Approved in the USA in September 2015, cariprazine is used to treat schizophrenia and acute manic or mixed episodes in bipolar I disorder, and is being explored for additional uses in treating negative symptoms of schizophrenia and bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: First Global Approval. McCormack, PL.[2018]

Cariprazine, a novel antipsychotic, has shown efficacy in treating both acute manic and mixed episodes of bipolar disorder, with effective doses ranging from 3-12 mg/day, and for bipolar depression, lower doses of 1.5-3 mg/day are beneficial as monotherapy.

Overall, cariprazine is well-tolerated, with common side effects including akathisia and nausea, but it does not present metabolic concerns, making it a promising treatment option for patients with bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials. Do, A., Keramatian, K., Schaffer, A., et al.[2022]

In clinical trials, cariprazine significantly improved schizophrenia symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a longer time to relapse in a long-term study.

Cariprazine was more effective than risperidone in treating negative symptoms of schizophrenia, which are often challenging to address, and it was generally well tolerated with mostly mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: A Review in Schizophrenia. Garnock-Jones, KP.[2018]

In a phase 3 study involving 493 adults with bipolar I disorder, cariprazine at a dose of 1.5 mg/day significantly reduced depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

The 3.0 mg/day dose did not show significant benefits over placebo, and the safety profile was consistent with previous studies, with common side effects including akathisia and nausea, but minimal weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Earley, WR., Burgess, MV., Khan, B., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cariprazine: First Global Approval. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Cariprazine for bipolar depression: What is the number needed to treat, number needed to harm and likelihood to be helped or harmed? [2020]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Mini Review on Cariprazine: A Promising Antipsychotic Agent. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Cariprazine: A Review in Schizophrenia. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study. [2018]

7. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. [2021]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cariprazine in Bipolar Depression and Mania: State of the Art. [2019]

9. Denmark pubmed.ncbi.nlm.nih.gov

Cariprazine in the treatment of Bipolar Disorder: A systematic review and meta-analysis. [2021]