What Is Cariprazine?
Cariprazine is an FDA-approved medication for the treatment of bipolar depression and schizophrenia. It is a second-generation antipsychotic medication, also known as an atypical antipsychotic. While the exact mechanism of how second-generation antipsychotics work is not fully understood, cariprazine is believed to help by affecting certain chemical messengers in the brain, such as dopamine and serotonin, which play a role in mood, thinking, and behavior. In clinical trials, cariprazine monotherapy has shown effectiveness in improving depressive symptoms, particularly in bipolar I depression, with studies reporting higher remission rates compared to placebo.
Beyond its approved uses, cariprazine is also being investigated for other conditions, including major depressive disorder, cocaine use disorder, and autism spectrum disorder. Studies have explored various doses and treatment durations, ranging from a single dose to several weeks of treatment.
Uses and Conditions Under Study
Cariprazine is currently being studied for a range of psychiatric conditions, with a significant focus on mood and thought disorders.
- Bipolar Disorder and Related Conditions: Cariprazine is FDA-approved for bipolar depression, a phase of bipolar disorder characterized by significant disability and a high risk of suicide. It is also being investigated for other aspects of bipolar disorder, including mania. A total of 20 trials have explored cariprazine for conditions such as Bipolar I Disorder, Bipolar Disorder, Mania, Bipolar Depression, and Depression, Bipolar.
- Schizophrenia: As an FDA-approved treatment for schizophrenia, cariprazine is being assessed for its safety and effectiveness in managing this severe psychiatric illness, which involves disturbances in cognition and thought. There are 14 trials dedicated to studying cariprazine for schizophrenia.
- Major Depressive Disorder (MDD): Cariprazine is under investigation as a potential treatment for MDD, a prevalent and debilitating condition marked by persistent sadness and loss of interest. Studies aim to assess its efficacy, sometimes as an add-on therapy to existing antidepressants. A combined 12 trials are exploring cariprazine for Major Depressive Disorder and Depression.
- Cocaine Use Disorder: Cariprazine is being explored for its potential role in treating cocaine use disorder, with 2 trials currently examining its effects in this area.
- Autism Spectrum Disorder: Research is also underway to understand if cariprazine can be beneficial for individuals with Autism Spectrum Disorder. There are 2 trials investigating this use.
Additionally, some trials have assessed cariprazine in specific populations, such as pediatric patients, to understand its safety and efficacy across different age groups.
Dosing
Cariprazine has been studied in various dosage forms and strengths, primarily as capsules and prolonged-release tablets. The typical administration is once daily.
For adults, a common starting dose observed in trials is 1.5 mg once daily, which can be adjusted by a psychiatrist up to a maximum dose of 4.5 mg, often with dose escalations occurring at two-week intervals. In some studies for depressive symptoms, cariprazine has been investigated at doses of 1.5 mg and 3 mg per day. Higher investigational doses, such as a single dose of 22 mg, have also been explored in specific research settings.
Cariprazine has been studied both as a monotherapy (used alone) and as an adjunctive therapy (added to other treatments, such as antidepressants). Various strengths have been investigated, including:
- 0.75 mg, 1.5 mg, 3.0 mg, 4.5 mg, and 6.0 mg per day.
- Dose ranges like 1-2 mg, 2-4.5 mg, 3-6 mg/day, 6-9 mg/day, and 6-12 mg/day.
Pediatric dosing has also been a focus of some trials, with cohorts studying cariprazine in younger participants, including those aged 10-17 years and 5-9 years, to assess safety and efficacy in these populations.
Side Effects
The most common side effect reported by patients taking Cariprazine in clinical trials was akathisia (a feeling of restlessness and an urge to move). 10.1% of patients on Cariprazine experienced akathisia, compared to 2.2% on placebo. Other common side effects included:
- Insomnia: 8.9% of patients taking Cariprazine experienced difficulty sleeping, compared to 6.3% on placebo.
- Nausea: 6.9% of patients on Cariprazine experienced nausea, compared to 5.2% on placebo.
- Extrapyramidal disorder (movement-related side effects): 6.9% of patients on Cariprazine experienced these disorders, compared to 4.8% on placebo.
- Dizziness: 5.3% of patients on Cariprazine experienced dizziness, compared to 3.7% on placebo.
- Constipation: 5.1% of patients on Cariprazine experienced constipation, compared to 3.5% on placebo.
- Restlessness: 5.0% of patients on Cariprazine experienced restlessness, compared to 1.5% on placebo.
Headache was reported by 8.2% of patients taking Cariprazine, which was slightly less than the 8.8% of patients on placebo who experienced headaches.
Currently Recruiting Trials
For patients interested in contributing to medical research, several clinical trials are currently recruiting participants to further understand and explore the potential of Cariprazine. These studies investigate its effects across various conditions and formulations, aiming to improve treatment options.
One ongoing study, NCT07185815, is a Phase 1/Phase 2 trial sponsored by Mapi Pharma Ltd. It is designed to evaluate a new once-a-month long-acting subcutaneous injection of Cariprazine Depot. This study assesses the pharmacokinetics, safety, and tolerability of escalating doses in participants eligible for oral Cariprazine treatment, specifically those with schizophrenia, bipolar I disorder, or major depressive disorder. It aims to enroll 24 participants across three cohorts.
Another important Phase 4 study, NCT05913947, sponsored by Aalborg University Hospital, compares Cariprazine with Lithium in the acute phase treatment of bipolar depression. This research seeks to understand the difference in treatment effect between the two medications over 8 weeks, using the Hamilton Ratings Scale for Depression. It plans to include 122 patients with bipolar depression.
AbbVie is sponsoring NCT04777357, a Phase 3 study focusing on pediatric participants aged 10 to 17 years with Bipolar I Disorder experiencing depressive episodes. This trial aims to assess changes in disease activity and adverse events with Cariprazine treatment. The study has a target enrollment of 380 participants.
Similarly, Gedeon Richter Plc. is conducting NCT03817502, a Phase 3 trial to evaluate the efficacy and safety of Cariprazine in adolescent participants, aged 13 to 17 years, with schizophrenia. This study is testing Cariprazine at dosages of 1.5 mg/d and 4.5 mg/d, with an enrollment goal of 330 adolescents.
Where to Participate
Clinical trials for Cariprazine are widely accessible, with studies recruiting across a broad geographic range. Currently, there are 79 sites located in 61 cities across 19 states, offering numerous opportunities for participation.
Some of the top locations with multiple recruiting sites include:
- Oklahoma City, Oklahoma (5 sites)
- Houston, Texas (4 sites)
- Atlanta, Georgia (3 sites)
- Miami, Florida (3 sites)
- Buffalo, New York (2 sites)
- Orange, California (2 sites)
- Orlando, Florida (2 sites)
- Cincinnati, Ohio (2 sites)
- Long Beach, California (2 sites)
- The Woodlands, Texas (2 sites)
Eligibility criteria for these studies generally specify participants between 10 and 65 years of age, with both male and female individuals welcome. It is important to note that these trials are not open to healthy volunteers, as they focus on individuals with specific medical conditions, including children and adolescents.
Development Timeline
The journey of Cariprazine through clinical development began on June 20, 2007, marking the start of its first clinical trial. Since then, a robust research program has unfolded, encompassing a total of 44 trials and enrolling over 17,284 participants to date, with studies projected to continue until December 5, 2025.
Early development was significantly driven by sponsors like Forest Laboratories, which led 19 trials, and AbbVie, involved in 10 studies. Gedeon Richter Plc. has also been a key contributor. The development pipeline has seen a progression through various phases, with 22 trials reaching Phase 3, 11 in Phase 2, 7 in Phase 4, and a few in Phase 1 or combined Phase 1/Phase 2 stages.
Initially, Cariprazine was explored for conditions such as IBS-C and hyperphosphatemia. However, its therapeutic focus quickly expanded to address a wide range of psychiatric disorders. The development timeline shows an evolution to include studies for Major Depressive Disorder, Bipolar Disorder, Mania, and Bipolar Depression. Further research broadened its scope to conditions like Schizophrenia, Cocaine Use Disorder, Autism Spectrum Disorder, and Generalized Anxiety Disorder, demonstrating a sustained commitment to exploring its potential across diverse mental health needs.