Cariprazine for ADHD

(ADHD Trial)

Overseen By Kathryn Fotinos, M.Psy

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Dr. Martin A. Katzman

Must be taking: Long-acting psychostimulants

Must not be taking: Antipsychotics

Disqualifiers: Psychotic disorders, Seizure disorder, others

Stay on Your Current Meds You can continue your current medications while participating

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: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding a low dose of cariprazine, an atypical antipsychotic, can aid adults with ADHD who do not find sufficient relief from their current long-acting psychostimulant medications. The focus is on improving symptoms for those who have tried standard treatments but continue to struggle with managing ADHD. Individuals who have maintained a stable dose of their current ADHD medication for over four weeks and still experience significant symptoms may be suitable candidates for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

You can continue taking your current long-acting psychostimulant and any other stable psychotropic medications, except antipsychotics. If you are using recreational drugs, including cannabis, you must stop at least 2 weeks before joining the study.

What is the safety track record for Cariprazine?

Research has shown that cariprazine is generally safe and well-tolerated for long-term use. Most studies have found mild side effects, such as restlessness or nausea. In one study, over 92% of participants completed their treatment without stopping due to side effects.

However, cariprazine may not be suitable for everyone. For instance, it might be risky for elderly patients with certain health issues. Additionally, animal studies have suggested it could harm an unborn baby. Therefore, discussing all potential risks with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Cariprazine is unique because it offers a new approach to treating ADHD by focusing on dopamine D3 receptors, which are less targeted by traditional ADHD treatments like stimulants (e.g., Adderall, Ritalin) and non-stimulants (e.g., Strattera). Researchers are excited about cariprazine because it may help reduce symptoms with potentially fewer side effects, particularly for patients who don't respond well to existing medications. By targeting different pathways in the brain, cariprazine presents a novel option that could complement existing therapies, offering hope for better management of ADHD symptoms.

What is the effectiveness track record for cariprazine as an adjunctive treatment for ADHD?

Research has shown that cariprazine effectively treats mental health conditions such as bipolar disorder and major depressive disorder. Studies have found that it significantly improves both depressive and manic episodes. Cariprazine also aids in daily activities and enhances overall quality of life. While primarily used for mood disorders, promising evidence suggests it can also assist with ADHD, particularly when standard medications fall short. This trial specifically investigates the effects of cariprazine as an additional treatment to common ADHD medications to enhance their effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Martin A Katzman, MD

Principal Investigator

Clinic Director

Are You a Good Fit for This Trial?

Inclusion Criteria

The participant has provided signed informed consent.

Males and/or females aged 18-70 (extremes included).

Participants with a primary diagnosis of ADHD according to DSM-5 (314.01) criteria (diagnosis to be made using the Mini-International Neuropsychiatric Interview (MINI) 7.0.2 and confirmed by the Diagnostic Interview for ADHD in Adults (DIVA 5.0). Participants with a comorbid anxiety and depressive disorder will be permitted, as long as ADHD is judged to be the primary diagnosis.

Exclusion Criteria

You have experienced a mental health disorder other than the one being studied in the past six months.

If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study, or intending to donate ova during such time period.

You have started or stopped taking any medication recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive adjunct treatment with cariprazine alongside their stable dose of psychostimulants

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cariprazine

How Is the Trial Designed?

Group I: Cariprazine treatment Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Dr. Martin A. Katzman

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

Cariprazine is a new medication approved by the FDA in 2015 for treating schizophrenia and type I bipolar disorder, showing efficacy in addressing positive, negative, and cognitive symptoms of schizophrenia without causing significant extrapyramidal side effects in animal models.

While cariprazine has a unique mechanism of action as a biased agonist at dopamine receptors, it can still cause mild to moderate side effects in humans, including akathisia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine:New dopamine biased agonist for neuropsychiatric disorders. De Deurwaerdère, P.[2017]

A comprehensive analysis of the FAERS database revealed 3,659 adverse events (AEs) related to Cariprazine, highlighting significant safety concerns, particularly involving eye disorders that were not previously listed in the drug's official leaflet.

The study identified 140 different types of AEs across 27 organ systems, underscoring the importance of ongoing post-market surveillance to ensure healthcare professionals are aware of potential new adverse drug reactions (ADRs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mining and analysis of adverse event signals of Cariprazine based on the real-world data of FAERS database. Zhu, H., Qu, Y., Du, Z., et al.[2023]

In a study involving 732 patients with erosive esophagitis, vonoprazan (VPZ) demonstrated high efficacy in healing the condition, achieving healing rates comparable to lansoprazole (LPZ) across all tested doses.

VPZ was found to be safe, with no significant safety concerns reported during the 8-week study, and a recommended effective dose of 20 mg once daily for treating severe erosive esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis. Ashida, K., Sakurai, Y., Nishimura, A., et al.[2018]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11421304/

Cariprazine in Psychiatry: A Comprehensive Review of ...

On the YMRS scale, the effectiveness was −6.1 [−8.4 to −3.8] in week 3 for a dose of 3–6 mg/day and −5.9 [−8.2, −3.6] for a dose of 6–12 mg/day.

2.

vraylarhcp.com

vraylarhcp.com/efficacy/bipolar-depression-efficacy

VRAYLAR® (cariprazine) Efficacy for Bipolar Depression

Overall, 65% of patients treated with cariprazine 1.5 mg/day or 3 mg/day had higher anxiety symptoms at baseline, defined as a HAM-D anxiety/somatization ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05933538

Effectiveness of Cariprazine Monotherapy for Treatment ...

The results demonstrated that Cariprazine was associated with significant improvements in depressive symptoms and functional outcomes in this population.

4.

tandfonline.com

tandfonline.com/doi/full/10.1080/13696998.2025.2513766

Real-world effectiveness of cariprazine in major depressive ...

The RCT results demonstrated a significant reduction in mean MADRS total score after 6 or 8 weeks of cariprazine treatment. Further, a post hoc analysis of the ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S1064748124005633

Effect of Cariprazine on Outcomes in Older-aged and ...

Conclusions. Cariprazine appears to be effective for both depressive and manic/mixed episodes of bipolar I disorder, regardless of age.

6.

media.allergan.com

media.allergan.com/actavis/actavis/media/allergan-pdf-documents/safety-data-sheets/VRAYLAR-FG00108-AGHS-EN.pdf

SAFETY DATA SHEET

Cariprazine Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

7.

vraylarhcp.com

vraylarhcp.com/safety

VRAYLAR® (cariprazine) Tolerability and Safety

Well-established safety profile across 3 bipolar I acute manic or mixed studies · Most common adverse reactions (≥5% and at least twice that of placebo) · >92% of ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2015/204370lbl.pdf

VRAYLAR™(cariprazine) capsules - accessdata.fda.gov

Based on animal data VRAYLAR may cause fetal harm. Administration of cariprazine to rats during the period of organogenesis caused malformations, lower pup ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5571492/

The safety and tolerability of cariprazine in long-term ...

In these post hoc pooled analyses of data from 2 long-term open-label studies, treatment with cariprazine was generally safe and well tolerated.

10.

mayoclinic.org

mayoclinic.org/drugs-supplements/cariprazine-oral-route/description/drg-20152634

Cariprazine (oral route) - Side effects & dosage

Cariprazine is used to treat schizophrenia or mania and depression related with bipolar disorder. It is also used to treat major depressive disorder (MDD).