524 Participants Needed

Clozapine vs Risperidone for Psychosis

Recruiting at 4 trial locations
AP
DB
EM
Overseen ByEmily McNeil
Age: 18 - 65
Sex: Any
Trial Phase: Phase 4
Sponsor: University of Texas Southwestern Medical Center
Must be taking: Antipsychotics
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

The CLOZAPINE study is designed as a multisite study across 5 sites and is a clinical trial, involving human participants who are prospectively assigned to an intervention. The study will utilize a stringent randomized, double-blinded, parallel group clinical trial design. B2 group will serve as psychosis control with risperidone as medication control. The study is designed to evaluate effect of clozapine on the B1 participants, and the effect that will be evaluated is a biomedical outcome. The study sample will be comprised of individuals with psychosis, including 1) schizophrenia, 2) schizoaffective disorder and 3) psychotic bipolar I disorder. The investigators plan to initially screen and recruit n=524 (from both the existing B-SNIP library and newly-identified psychosis cases, \~50% each) in order to enroll n=320 (B1 and B2) into the RCT.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect EEG properties or interact with the study drugs, such as lithium, anticonvulsants, benzodiazepines, and some antibiotics and seizure medications. If you are on these, you may need to discontinue them safely before participating.

What safety data exists for Clozapine and Risperidone?

Clozapine can cause serious blood disorders, seizures, heart problems, and weight gain, and requires regular blood monitoring to manage risks. Risperidone is generally considered safer but may still have side effects like weight gain and metabolic changes.12345

How does the drug clozapine differ from other treatments for psychosis?

Clozapine is unique because it is specifically effective for treatment-resistant schizophrenia, meaning it works for patients who do not respond to other antipsychotic drugs. Unlike many other antipsychotics, clozapine has a low D2-blocking effect, which can make it necessary to combine it with other medications to fully manage symptoms.46789

What data supports the effectiveness of the drugs clozapine and risperidone for treating psychosis?

Clozapine has been shown to be effective in up to 60% of patients with treatment-resistant schizophrenia, and it provides significant symptom improvement over other second-generation antipsychotic drugs. Risperidone may be equally effective as clozapine in some cases, but more research is needed to confirm this.69101112

Who Is on the Research Team?

CT

Carol A Tamminga, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with schizophrenia, schizoaffective disorder, or bipolar I with psychotic features. Participants must be medically stable, have a certain level of symptom severity, and not belong to vulnerable groups like pregnant women. They shouldn't have used clozapine before or certain long-acting antipsychotics recently.

Inclusion Criteria

Able to provide written informed consent
Able to read, speak, and understand English
My health condition is currently stable.
See 3 more

Exclusion Criteria

You have had a severe allergic reaction called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Drug-Induced Hypersensitivity Syndrome (DIHS) in the past.
I do not have severe neurological or medical conditions affecting my brain.
You are currently having thoughts about hurting someone and have a detailed plan on how to do it, which means you cannot receive treatment as an outpatient.
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive clozapine or risperidone treatment, with concomitant medications for symptomatic management

14 weeks
Regular visits for monitoring and dose adjustments

Stable Treatment

Participants continue on a stable dose of clozapine or risperidone

8 weeks
Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Clozapine
  • Risperidone
Trial Overview The study compares the effects of clozapine versus risperidone on individuals with specific types of psychosis. It's a rigorous test where participants are randomly assigned to one of the drugs in a controlled environment across multiple sites to see which drug works better for their condition.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Biotype 1 - Clozapine (B1C)Experimental Treatment1 Intervention
Target doses will be up to clozapine 500mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].
Group II: Biotype 2 - Clozapine (B2C)Active Control1 Intervention
Target doses will be up to clozapine 500mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].
Group III: Biotype 1 - Risperidone (B1R)Placebo Group1 Intervention
Target doses will be up to risperidone 6mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].
Group IV: Biotype 2 - Risperidone (B2R)Placebo Group1 Intervention
Target doses will be up to risperidone 6mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day

Clozapine is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Clozaril for:
  • Schizophrenia
  • Borderline Personality Disorder
  • Paranoid Disorder
🇪🇺
Approved in European Union as Clozapine for:
  • Schizophrenia
  • Treatment-resistant schizophrenia

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials
1,102
Recruited
1,077,000+

University of Georgia

Collaborator

Trials
109
Recruited
43,500+

Hartford Hospital

Collaborator

Trials
140
Recruited
19,700+

National Institute of Mental Health (NIMH)

Collaborator

Trials
3,007
Recruited
2,852,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials
872
Recruited
12,930,000+

University of Chicago

Collaborator

Trials
1,086
Recruited
844,000+

Published Research Related to This Trial

In a study of 24 chronically institutionalized patients with refractory schizophrenia, clozapine was found to be more effective than risperidone, with 58% of patients responding to clozapine compared to only 25% responding to risperidone.
Clozapine showed significant improvements in managing aggressive behavior (71% response) and positive symptoms (38% response), while risperidone had lower response rates across all symptom domains, suggesting that clozapine remains the gold standard for treatment despite the better risk/benefit profile of risperidone.
Comparative efficacy of risperidone and clozapine in the treatment of patients with refractory schizophrenia or schizoaffective disorder: a retrospective analysis.Sharif, ZA., Raza, A., Ratakonda, SS.[2019]
Clozapine is more effective than other second-generation antipsychotic drugs in improving symptoms for patients with schizophrenia who have not responded to two or more previous treatments, as shown by a significant reduction in the PANSS total score in a study of 136 participants over one year.
While clozapine did not show a significant advantage in Quality of Life scores compared to other SGAs, it was associated with fewer extrapyramidal side effects and reported better mental health by participants at 12 weeks, indicating a favorable safety profile.
Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia.Lewis, SW., Barnes, TR., Davies, L., et al.[2022]
Risperidone may serve as an effective alternative to clozapine for treating refractory schizophrenia, as shown in a study with 19 participants over 10 weeks, where both medications led to clinical improvements without significant differences in outcomes.
The study found that both treatments resulted in similar levels of symptom reduction and patient satisfaction, suggesting that further larger-scale trials are needed to confirm these findings and explore the potential of risperidone as a standard treatment option.
Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.Wahlbeck, K., Cheine, M., Tuisku, K., et al.[2022]

Citations

Comparative efficacy of risperidone and clozapine in the treatment of patients with refractory schizophrenia or schizoaffective disorder: a retrospective analysis. [2019]
Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. [2022]
Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study. [2022]
Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. [2013]
Risperidone augmentation of clozapine. [2013]
A review of clozapine safety. [2013]
Newer atypical antipsychotic medication versus clozapine for schizophrenia. [2018]
[Leponex, 10 years after -- a clinical review]. [2020]
Risperidone augmentation of clozapine: a critical review. [2022]
The clinical value of risperidone and olanzapine: A meta-analysis of efficacy and safety. [2014]
11.United Statespubmed.ncbi.nlm.nih.gov
Managing treatment-resistant schizophrenia: evidence from randomized clinical trials. [2019]
Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial. [2022]
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