What is the mechanism of action of this treatment?

Common treatments for schizophrenia, such as clozapine, primarily work by modulating neurotransmitter activity, particularly dopamine and serotonin. Clozapine, for instance, is effective in reducing symptoms of schizophrenia and associated violent behavior by blocking dopamine D2 receptors and serotonin 5-HT2A receptors. This dual action helps to balance the neurotransmitter levels in the brain, which is crucial for alleviating both positive symptoms (like hallucinations and delusions) and negative symptoms (such as social withdrawal and apathy). This modulation is essential for improving overall functioning and quality of life in schizophrenia patients.

What side effects are associated with this type of intervention?

Clozapine, a second-generation antipsychotic, is effective for treatment-resistant schizophrenia but has notable side effects including agranulocytosis (a potentially life-threatening decrease in white blood cells), myocarditis, seizures, and significant weight gain. Other common side effects are sedation, constipation, and hypersalivation. First-generation antipsychotics, like haloperidol, often cause extrapyramidal symptoms (EPS) such as akathisia, dystonia, and parkinsonism, as well as tardive dyskinesia. Second-generation antipsychotics, like risperidone and olanzapine, generally have a lower risk of EPS but can lead to metabolic side effects such as weight gain, diabetes, and dyslipidemia.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia. First-generation antipsychotics, such as chlorpromazine and haloperidol, primarily target dopamine receptors to reduce psychotic symptoms. Second-generation antipsychotics, including risperidone, olanzapine, quetiapine, and aripiprazole, offer broader neurotransmitter modulation, affecting both dopamine and serotonin pathways. Clozapine, a second-generation antipsychotic, is particularly noted for its efficacy in treatment-resistant schizophrenia and reducing violent behavior, although it requires careful monitoring due to potential severe side effects like agranulocytosis. These medications have shown varying degrees of effectiveness in managing both positive and negative symptoms of schizophrenia.

What other types of research exist?

Promising novel alternatives to Clozapine for schizophrenia patients include second-generation antipsychotics such as Risperidone, Olanzapine, and Aripiprazole. These medications have shown a favorable balance of efficacy and side effects. Additionally, emerging treatments like Pimavanserin, which targets serotonin receptors, and VMAT2 inhibitors like Deutetrabenazine, are being explored for their potential benefits in managing psychosis and associated behaviors.

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Atypical Antipsychotic

Clozapine for Schizophrenia (REVISIT-C Trial)

Phase 4

Recruiting

Led By Ragy Girgis, MD

Research Sponsored by New York State Psychiatric Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

An unstable of serious medical or neurological condition including a myeloproliferative disorder or condition that surprises the bone marrow

A history of intellectual impairment

Timeline

Screening 3 days

Treatment Varies

Follow Up 14 days

Awards & highlights

Pivotal Trial

All Individual Drugs Already Approved

Approved for 10 Other Conditions

Drug Has Already Been Approved

No Placebo-Only Group

Summary

This trial is testing whether clozapine can reduce violent behavior more effectively than usual treatments in adults with schizophrenia who have recently been violent. Clozapine helps by balancing brain chemicals to manage symptoms. The study will last for several months and include regular medical check-ups. Clozapine has been shown to reduce violent and aggressive behavior in patients with schizophrenia, especially those who are treatment-resistant.

Who is the study for?

This trial is for adults with schizophrenia or schizoaffective disorder who have been violent recently. They must be medically stable, able to consent, and not on certain long-term medications. Pregnant women, those intolerant to clozapine, with serious medical conditions or high suicide risk are excluded.

What is being tested?

The study compares the effectiveness of clozapine versus usual antipsychotic treatments in reducing violence among individuals with schizophrenia over a 24-week period across seven sites. Participants will be randomly assigned to one of the two treatment groups.

What are the potential side effects?

Clozapine can cause side effects like drowsiness, increased saliva production, constipation, and more severe issues such as low white blood cell count (which can increase infection risk), heart inflammation or bowel obstruction in those allergic.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have a serious condition affecting my blood or nervous system.

Select...

I have a history of intellectual impairment.

Select...

I tried clozapine without success or had side effects.

Timeline

Screening ~ 3 days6 visits

Treatment ~ Varies

Follow Up ~ 14 days1 visit

Screening ~ 3 days

Treatment ~ Varies

Follow Up ~14 days

This trial's timeline: 3 days for screening, Varies for treatment, and 14 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Effectiveness outcome: Violent acts

Syndrome

Secondary study objectives

Effect on aggression

Alcohol or Other Drugs use

Other study objectives

Interventions to Prevent Violence

Side effects data

From 2008 Phase 4 trial • 25 Patients • NCT00001656

70%

tachycardia >100 beats/min (supine)

67%

Hypersalivation

64%

Hypertension

42%

Enuresis

33%

Increased appetite

33%

Difficulty concentrating

25%

Insomnia

17%

Abnormal white blood count

17%

Somnolence

17%

Constipation

10%

Tachycardia >120 beats/min (supine)

100%

80%

60%

40%

20%

Study treatment Arm

Clozapine Group

Olanzapine Group

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: ClozapineExperimental Treatment1 Intervention

treatment with clozapine naturalistically administered (as per clinical guideline).

Group II: Treatment as usualActive Control1 Intervention

open label naturalistic treatment as usual with any antipsychotic other than clozapine

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Clozapine

FDA approved

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for schizophrenia, such as clozapine, primarily work by modulating neurotransmitter activity, particularly dopamine and serotonin. Clozapine, for instance, is effective in reducing symptoms of schizophrenia and associated violent behavior by blocking dopamine D2 receptors and serotonin 5-HT2A receptors. This dual action helps to balance the neurotransmitter levels in the brain, which is crucial for alleviating both positive symptoms (like hallucinations and delusions) and negative symptoms (such as social withdrawal and apathy). This modulation is essential for improving overall functioning and quality of life in schizophrenia patients.

Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease.Antisuicide properties of psychotropic drugs: a critical review.Schizophrenia - advances in drug therapy.