SchizophreniaPhase 4NCT00330551

Oral Versus Injectable Risperidone for Treating First-Episode Schizophrenia

A Phase 4 study testing Oral Risperidone and Risperidone in Long-Acting Injectable Form (Consta) in people with Schizophrenia, run by University of California, Los Angeles at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia
What is being tested?: Oral Risperidone and Risperidone in Long-Acting Injectable Form (Consta)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 126 participants
Where: 1 siteUnited States
Study dates: Mar 2006to Nov 2012
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

DSM-IV diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder
First major episode of psychotic symptoms occurred within 2 years prior to study entry
Participant in the UCLA Center for Neurocognition and Emotion in Schizophrenia

Who cannot join

Neurological disorder or injury (e.g., encephalitis, epilepsy, traumatic brain injury)
Mental retardation (e.g., premorbid IQ less than 70)
Significant alcohol or substance abuse within 6 months prior to study entry
Inability to complete research measures in English
Any condition that may make risperidone use medically inadvisable

Trial locations and contacts

1 site in 1 country.

United States1 site

Semel Institute for Neuroscience and Human Behavior at UCLA
Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Effects of Risperdal Consta Versus Oral Antipsychotic Medication on Clinical and Functional Outcome and Neurocognition in First-episode Schizophrenia

This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia.

Read the detailed description

Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. Proper treatment of first-episode schizophrenia may increase the chances of controlling disease progression on a long-term basis. People experiencing their first episode of schizophrenia are more responsive to treatment than those with chronic schizophrenia, but are also more susceptible to adverse treatment side effects. Atypical antipsychotic medications have been shown to produce fewer adverse side effects than older "typical" antipsychotics. Risperidone is a type of atypical antipsychotic medication that is used to control the symptoms of schizophrenia. This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia.

Participants in this open label study will be randomly assigned to receive either orally administered risperidone or long-acting risperidone administered via injection. Participants assigned to oral risperidone will receive medication in doses that are determined to be optimal by the study psychiatrist. Participants assigned to long-acting risperidone will receive an injection of risperidone once every 2 weeks. Dosages will begin at 25 mg and will be adjusted as necessary to achieve the optimal dosage. Following 2 to 3 months to achieve outpatient risperidone dosage stabilization, the randomized medication conditions will begin and participants will be monitored for 1 year. Study visits will occur once weekly throughout the study. They will include group therapy meetings focused on everyday living skills; family education about schizophrenia; assessments of medication response; and individual meetings with a case manager for counseling and evaluations of schizophrenia symptoms.

Conditions: Schizophrenia
Being tested: Oral Risperidone, Risperidone in Long-Acting Injectable Form (Consta)
Keywords: Schizoaffective Disorder, Depressed Type, Schizophreniform Disorder, First-episode Schizophrenia, Injectable Risperidone
Medical subject headings: Schizophrenia, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral RisperidoneDrug
Also called Risperdal
Patients will be treated with oral risperidone daily, with the dosage determined by treating psychiatrist.
Risperidone in Long-Acting Injectable Form (Consta)Drug
Also called Risperdal Consta
Participants will take a 25 mg dosage of injectable risperidone (Risperidone in Long-Acting Injectable Form (Consta)) once every 2 weeks. Dosage will be adjusted if needed.

Study groups in NCT00330551
Study group	Role	What they receive
Long-acting injectible risperidone	Experimental	Participants who are randomly assigned to this arm will be administered the long-acting injectible form of risperidone (Risperdal Consta) every two weeks, plus group skills training and case management, for 12 months. Receives: Drug: Risperidone in Long-Acting Injectable Form (Consta)
Oral risperidone	Active comparator	Participants who are randomly assigned to this arm will be treated with the oral version of risperidone (Risperdal) daily, plus group skills training and case management, for 12 months. Receives: Drug: Oral Risperidone

What is being measured

The primary outcome is the main question the study is designed to answer.

Medication Adherence
5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, MEMS cap readings, plasma assays, and psychiatrist judgments for oral risperidone and timing of injections for long-acting injectable risperidone averaged over study participation
Measured: Measured weekly throughout study participation, averaged over study participation
Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms
Dichotomous measure: Presence of any of three psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring any time after randomization and until end of study participation (up to 12 mos.).
Measured: Occurrence after randomization and until end of study participation (up to 12 mos.)
Number of Participants Who Returned to Work or School (SAS Work Section)
The Social Adjustment Scale records the return to work or school and the number of weeks in work or school during each 3-month period. For this outcome, outcome as dichotomized as 0 if an individual did not return to work or school and 1 if they did return to competitive work or regular school enrollment.
Measured: Measured from Baseline to Month 12
Number of Weeks Maintaining Work or School (SAS)
Measured as the number of weeks in which a participant has competitive employment or attends regular school courses. Possible range is 0 to 52 weeks.
Measured: Cumulative total measured from Baseline to Month 12
Change in Global Functioning Scale: Role
10-point scale of work/school functioning. Scale range is from 1 (extreme role dysfunction) to 10 (superior role functioning). Measured by subtracting the baseline rating from the rating at 12 months.
Measured: Measured at Baseline and Month 12

Secondary outcomes (4)

MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score
The MCCB Overall Composite T score is computed by the MCCB Computer Scoring Program from the raw scores for 10 individual cognitive tests. The mean for the general population of comparable age and sex is 50 with a standard deviation of 10. Higher scores indicate better cognitive functioning. The outcome measure was the change from baseline to 12 months, calculated as 12-month T score minus baseline T score. Higher values indicate better outcome.
Measured: Measured at baseline and 12 months
Emotional Reactivity on Psychophysiological Measures
Electrodermal reactivity to pictures of negative versus neutral stimuli was the initially proposed measure. Larger skin conductance increases in response to negative pictures compared to neutral pictures would indicate stronger emotional reactivity.
Measured: Measured from Baseline to Month 12
Retention in Treatment
Number of days on the randomized medication before being switched to a different antipsychotic medication or dropping out of the medication trial. Possible range is 0 to 365, with higher numbers indicating better retention in treatment.
Measured: From baseline to 12 months
Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R)
Rating scale based on clinician's interview of patient to determine level of lack of awareness of having a mental disorder. Range is from 1 (Aware) to 5 (Unaware), so lower scores indicate better outcome.
Measured: Baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2006Nov 2012

First posted29 May 2006 (estimated)
Study startMar 2006
Primary completionNov 2012
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of California, Los AngelesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 126 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00330551
Sponsor's protocol ID: P50MH066286
Other IDs: P50MH066286, DATR A2-AISZ, Janssen RIS-NAP-4009
Status last verified: Feb 2023
First submitted: 26 May 2006
Last updated: 1 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Novacek DM, Subotnik KL, Ventura J, Casaus LR, Whelan F, Sugar CA, Nuechterlein KH. Positive symptoms and medication adherence in response to oral versus long-acting injectable risperidone in black, latino, and white first-episode psychosis patients. Schizophr Res. 2025 Oct;284:160-166. doi: 10.1016/j.schres.2025.08.004. Epub 2025 Aug 7.
PubMed 40779812
Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, Marder S, Nuechterlein KH. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial. JAMA Psychiatry. 2015 Aug;72(8):822-9. doi: 10.1001/jamapsychiatry.2015.0270.
PubMed 26107752
Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011 Oct;132(1):35-41. doi: 10.1016/j.schres.2011.06.029. Epub 2011 Jul 20.
PubMed 21767934

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Risperdal Consta Versus Oral Antipsychotic Medication on Clinical and Functional Outcome and Neurocognition in First-episode Schizophrenia
ClinicalTrials.gov ID: NCT00330551
Acronym / sponsor ID: P50MH066286
Conditions: Schizophrenia
Keywords: Schizoaffective Disorder, Depressed Type, Schizophreniform Disorder, First-episode Schizophrenia, Injectable Risperidone
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 126 participants (actual)
Lead sponsor: University of California, Los AngelesUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH), Janssen Scientific Affairs, LLC
Study start: Mar 2006
Primary completion: Nov 2012 (actual)
Study completion: Nov 2012 (actual)
First posted: 29 May 2006 (estimated)
Results: Posted 23 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will determine the effectiveness of oral risperidone versus long-acting injectable risperidone in treating people with first-episode schizophrenia.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Long-acting injectible risperidone	Experimental	Drug: Risperidone in Long-Acting Injectable Form (Consta)Participants who are randomly assigned to this arm will be administered the long-acting injectible form of risperidone (Risperdal Consta) every two weeks, plus group skills training and case management, for 12 months.
Oral risperidone	Active comparator	Drug: Oral RisperidoneParticipants who are randomly assigned to this arm will be treated with the oral version of risperidone (Risperdal) daily, plus group skills training and case management, for 12 months.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

DSM-IV diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder
First major episode of psychotic symptoms occurred within 2 years prior to study entry
Participant in the UCLA Center for Neurocognition and Emotion in Schizophrenia

Key exclusion criteria (5 listed)

Neurological disorder or injury (e.g., encephalitis, epilepsy, traumatic brain injury)
Mental retardation (e.g., premorbid IQ less than 70)
Significant alcohol or substance abuse within 6 months prior to study entry
Inability to complete research measures in English
Any condition that may make risperidone use medically inadvisable

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Oral RisperidoneAlso: RisperdalPatients will be treated with oral risperidone daily, with the dosage determined by treating psychiatrist.	Drug	Oral risperidone
Risperidone in Long-Acting Injectable Form (Consta)Also: Risperdal ConstaParticipants will take a 25 mg dosage of injectable risperidone (Risperidone in Long-Acting Injectable Form (Consta)) once every 2 weeks. Dosage will be adjusted if needed.	Drug	Long-acting injectible risperidone

Primary outcome

Medication Adherence
Time frame: Measured weekly throughout study participation, averaged over study participation
5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, MEMS cap readings, plasma assays, and psychiatrist judgments for oral risperidone and timing of injections for long-acting injectable risperidone averaged over study participation
Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms
Time frame: Occurrence after randomization and until end of study participation (up to 12 mos.)
Dichotomous measure: Presence of any of three psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring any time after randomization and until end of study participation (up to 12 mos.).
Number of Participants Who Returned to Work or School (SAS Work Section)
Time frame: Measured from Baseline to Month 12
The Social Adjustment Scale records the return to work or school and the number of weeks in work or school during each 3-month period. For this outcome, outcome as dichotomized as 0 if an individual did not return to work or school and 1 if they did return to competitive work or regular school enrollment.
Number of Weeks Maintaining Work or School (SAS)
Time frame: Cumulative total measured from Baseline to Month 12
Measured as the number of weeks in which a participant has competitive employment or attends regular school courses. Possible range is 0 to 52 weeks.
Change in Global Functioning Scale: Role
Time frame: Measured at Baseline and Month 12
10-point scale of work/school functioning. Scale range is from 1 (extreme role dysfunction) to 10 (superior role functioning). Measured by subtracting the baseline rating from the rating at 12 months.

4 secondary outcomes

MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T Score
Time frame: Measured at baseline and 12 months
Emotional Reactivity on Psychophysiological Measures
Time frame: Measured from Baseline to Month 12
Retention in Treatment
Time frame: From baseline to 12 months
Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder-Revised (SUMD-R)
Time frame: Baseline to 12 months

Results and safety

Results posted to the registry on 23 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Long-acting Injectable Risperidone	40	30
Oral Risperidone	43	27

Primary outcome: Medication Adherence

Time frame: Measured weekly throughout study participation, averaged over study participation. Mean (Standard Deviation). Unit: units on a scale

Measure	Long-acting Injectable Risperidone n = 40	Oral Risperidone n = 43
Value	1.1 (0.5)	1.9 (0.8)

Long-acting Injectable Risperidone vs Oral Risperidone: t-test: .77 (95% CI 0.483 to 1.058), p =.05, t-test, 2 sided

Primary outcome: Number of Participants Who Had an Exacerbation or Relapse of Psychotic Symptoms

Time frame: Occurrence after randomization and until end of study participation (up to 12 mos.). Count of participants. Unit: Participants

Measure	Long-acting Injectable Risperidone n = 40	Oral Risperidone n = 43
Value	2	14

Long-acting Injectable Risperidone vs Oral Risperidone: Risk Difference (RD): 11.1, p =.001, Chi-squared

Population analysed: All participants randomized to long-acting injectable or oral risperidone

Primary outcome: Number of Participants Who Returned to Work or School (SAS Work Section)

Time frame: Measured from Baseline to Month 12. Count of participants. Unit: Participants

Measure	Long-acting Injectable Risperidone n = 37	Oral Risperidone n = 38
Value	29	29

Long-acting Injectable Risperidone vs Oral Risperidone: p =.83, Chi-squared

Population analysed: All participants with data regarding return to work or school

Primary outcome: Number of Weeks Maintaining Work or School (SAS)

Time frame: Cumulative total measured from Baseline to Month 12. Mean (Standard Deviation). Unit: weeks

Measure	Long-acting Injectable Risperidone n = 37	Oral Risperidone n = 41
Value	26.7 (20.4)	21.1 (18.0)

Long-acting Injectable Risperidone vs Oral Risperidone: p =.20, ANOVA

Population analysed: All participants with data on duration of work or school

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Long-acting Injectible Risperidone	2 of 40 (5%)	11 of 40 (27.5%)	Not reported
Oral Risperidone	8 of 43 (18.6%)	19 of 43 (44.2%)	Not reported

Limitations and caveats (from the sponsor): This trial used oral risperidone as the comparator to allow a strong comparison between oral and long-acting injectable forms of the same drug. Generalization of results to other oral antipsychotic medications was not assessed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40779812Novacek DM, Subotnik KL, Ventura J, Casaus LR, Whelan F, Sugar CA, Nuechterlein KH. Positive symptoms and medication adherence in response to oral versus long-acting injectable risperidone in black, latino, and white first-episode psychosis patients. Schizophr Res. 2025 Oct;284:160-166. doi: 10.1016/j.schres.2025.08.004. Epub 2025 Aug 7.
Derived from this study: PubMed 26107752Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, Marder S, Nuechterlein KH. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial. JAMA Psychiatry. 2015 Aug;72(8):822-9. doi: 10.1001/jamapsychiatry.2015.0270.
Derived from this study: PubMed 21767934Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011 Oct;132(1):35-41. doi: 10.1016/j.schres.2011.06.029. Epub 2011 Jul 20.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Keith H. Nuechterlein, PhD principal investigator

University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Oral Risperidone and Risperidone in Long-Acting Injectable Form (Consta) in people with Schizophrenia, run by University of California, Los Angeles at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Medication Adherence (time frame: Measured weekly throughout study participation, averaged over study participation). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00330551, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023; AzTrials last refreshed its copy on 27 Oct 2026.