Aripiprazole, Risperidone, and Clozapine for Schizophrenia

(BEEST Trial)

Overseen By Cristina Gonzalez

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwell Health

Must be taking: Antipsychotics

Must not be taking: Psychotropics

Disqualifiers: Neurological, Endocrine, Suicidal, Substance 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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests three antipsychotic medications—Aripiprazole, Risperidone, and Clozapine—to determine which is most effective for individuals experiencing their first episode of psychosis, a condition where distinguishing reality becomes challenging. Researchers focus on participants with specific genetic markers that might enhance their response to these medications. The goal is to identify if one treatment is more effective for certain genetic profiles. This trial suits those who have recently started experiencing psychosis symptoms and have taken antipsychotic drugs for less than four weeks. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, allowing researchers to understand its benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have taken antipsychotic drugs for a total of 4 weeks or less in your lifetime. If you are on medications with psychotropic effects, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that aripiprazole, clozapine, and risperidone are generally safe and well-tolerated for treating schizophrenia.

Studies have found aripiprazole to be safe for long-term use. Patients using long-acting aripiprazole have not exhibited new safety issues, and it effectively stabilizes symptoms.

Clozapine is known for its safety and effectiveness, particularly for those unresponsive to other treatments. It often excels in managing symptoms and reducing hospital stays.

Risperidone studies confirm its safety, but some risks exist. Risperidone carries a higher chance of movement disorders compared to aripiprazole, although heart and metabolic risks are similar.

All three medications have proven effective for schizophrenia, providing reassurance about their safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study's treatments?

Researchers are excited about these treatments for schizophrenia because each offers unique benefits. Aripiprazole is known for its partial dopamine agonist action, which can reduce side effects typically associated with other antipsychotics. Clozapine stands out for its effectiveness in treatment-resistant cases of schizophrenia, offering hope for patients who haven't responded to other medications. Risperidone is praised for its ability to treat both positive and negative symptoms of schizophrenia, potentially improving overall patient outcomes. These diverse mechanisms provide new avenues for managing schizophrenia, giving researchers hope for more personalized and effective treatment options.

What evidence suggests that this trial's treatments could be effective for schizophrenia?

This trial will compare the effectiveness of aripiprazole, clozapine, and risperidone in treating schizophrenia. Studies have shown that all three treatments effectively manage the condition. Participants may receive aripiprazole, which can significantly help with both positive symptoms (like hallucinations) and negative symptoms (such as lack of motivation). Another group will receive clozapine, which research shows is particularly beneficial for those unresponsive to other treatments, with about 40% to 70% of these patients improving. The third group will receive risperidone, which has been shown to reduce symptom severity and enhance overall well-being over time. These treatments are well-proven in managing schizophrenia and have been supported by extensive research for their effectiveness. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18 to 35 experiencing their first episode of psychosis, with specific genetic markers and preserved brain connectivity. They must have taken antipsychotic drugs for no more than 4 weeks and be able to consent. Exclusions include serious neurological/endocrine disorders, MRI contraindications, pregnancy, high suicide risk, intellectual disability (IQ <71), recent substance abuse (except nicotine or mild alcohol/cannabis use), psychotropic medication need, prior psychosurgery or seizure disorder.

Inclusion Criteria

Preserved striatal connectivity, as determined by screening MRI scan

Ability to provide informed consent

I do not have the high-risk MC4R gene variant.

Exclusion Criteria

I have a serious brain or hormone disorder that could affect study results.

Contraindications to MRI (e.g. pacemaker)

I am able to understand and give consent for my participation.

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 treatment with either clozapine or FL-APs (risperidone or aripiprazole) for 12 weeks

12 weeks

Regular visits as per protocol

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

• Aripiprazole
• Clozapine
• Risperidone

Trial Overview The study tests how well participants with early schizophrenia respond to aripiprazole, risperidone or clozapine based on their genetic makeup. It aims to identify biomarkers that predict better treatment outcomes in those newly diagnosed with psychosis.

How Is the Trial Designed?

Group I: risperidone Active Control 1 Intervention

risperidone treatment provided per protocol

Group II: clozapine Active Control 1 Intervention

clozapine treatment per protocol

Group III: aripiprazole Active Control 1 Intervention

aripiprazole treatment per protocol

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11562632/

Long-term effectiveness of aripiprazole once monthly on ... Aripiprazole once-monthly (AOM) has proven effective in the treatment of schizophrenia, although little is known about its impact on global functioning and ...

2. nature.com nature.com/articles/s41537-025-00637-7

Long-term outcomes of Aripiprazole long-acting injectable However, there is a relative scarcity of data on the real-world effectiveness of newer LAIs and particularly of Aripiprazole long-acting ...

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.877867/full

Long-Term Real-World Effectiveness of Aripiprazole Once- ... Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium. Ann Gen ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0920996416301852

Therapeutic effectiveness and tolerability of aripiprazole as ... Results. As compared to baseline, patients treated with aripiprazole (mean dose 9.6 mg) improved significantly on measures of positive (p < 0.001), negative ...

5. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-04893-8

Improvement of functioning in patients with schizophrenia Treatment with the long-acting injectable antipsychotic aripiprazole once-monthly (AOM) may help improve functioning.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37672016/

Safety and Efficacy of Aripiprazole 2-Month Ready-to-Use ... Conclusions: Ari 2MRTU 960 was well tolerated in clinically stable patients with schizophrenia, with efficacy similar to AOM 400. Trial ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01149655

Efficacy & Safety Study of Oral Aripiprazole in Adolescents ... Participants stabilized on aripiprazole (trial drug) within the approved dose range of 10 to 30 mg/day and are tolerable based on clinical judgment.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0920996425001628

Stability of psychotic symptoms and safety in switching to ... Long-acting injectable aripiprazole has substantiated safety and efficacy in treating schizophrenia. However, interindividual variability in clinical ...

9. psychiatrist.com psychiatrist.com/jcp/long-term-safety-of-aripiprazole-lauroxil/

Long-Term Outcomes of Aripiprazole Lauroxil for Patients ... After the first 52 weeks, safety assessments revealed no new safety concerns and were consistent with the known safety profile of aripiprazole.