Optimizing Response in Psychosis Study (ORP)

The purpose of this project is to evaluate the efficacy of long-acting risperidone for patients with first episode schizophrenia spectrum who did not improve sufficiently with the first antipsychotic medication they tried during their initial treatment trial.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Psychotic Disorder Not Otherwise Specified
• Intervention / Treatment: Drug: long-acting injectable risperidone

Detailed Description

The goal of the proposed pilot study is to investigate the feasibility and efficacy of the long-acting injectable form of the second generation antipsychotic, risperidone, for the treatment of first episode patients who fail to respond to 12 weeks of treatment with an oral antipsychotic. The rationale for using this long-acting medication is that it eliminates covert non-adherence, which may be a factor in poor response. In addition, pharmacokinetic and pharmacodynamic differences between injectable and oral formulations may result in differences in treatment response favoring the injectable form. Subjects who have not responded sufficiently to treatment with an antipsychotic will be approached for the proposed long-acting risperidone trial. Risperidone treatment will be open label with titration based upon individual response (within FDA approved dose ranges). Treatment will begin with a phase of supplementation with oral risperidone. Subjects will stop their previous antipsychotic, start 2 mg of oral risperidone per day for one day and then increase the dose to 4 mg per day. Subjects who tolerate one week of oral risperidone will then begin injections of 25 mg long-acting risperidone every 2 weeks for a total of 12 weeks. If clinically indicated, the dose may be increased up to a maximum of 50 mg as per FDA guidelines.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Glen Oaks, New York, United States, 11004
      • The Zucker Hillside Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Current DSM-IV-defined diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychotic disorder NOS as assessed using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I/P) (First et al, 1998)
• Is in the first episode of illness. First episode is defined as having had 6 months or less of lifetime treatment with an antipsychotic.
• Has not responded sufficiently to treatment with an antipsychotic. Lack of response is defined as a rating at study entry of 4 (moderate) or more on at least one of the following BPRS-A items: conceptual disorganization, grandiosity, hallucinatory behavior, unusual thought content.
• Continuous antipsychotic treatment at the time of study entry of a minimum of 12 weeks with the same antipsychotic agent.
• Antipsychotic dosing at some point during the 12 weeks must have reached a sufficient dose for antipsychotic response (e.g. patients who received only low dose quetiapine for insomnia or anxiety would not qualify). Sufficient dose for second generation antipsychotics is defined as a minimum dose of risperidone 3 mg/day, olanzapine 10 mg/day, quetiapine 500 mg/day, ziprasidone 100 mg/day or aripiprazole 15 mg/day. Sufficient dose for first generation antipsychotics is defined as 3 mg/day of haloperidol or its equivalent for other first generation agents.
• Aged 15 to 40.
• If age 18 or older, competent and willing to sign informed consent.
• If under age 18, parent or guardian consent and subject assent.
• For women, a negative urine pregnancy test and agreement to use a medically accepted method of birth control.

Exclusion criteria:

• Meets DSM-IV criteria for a current substance-induced psychotic disorder, a psychotic disorder due to a general medical condition, delusional disorder, brief psychotic disorder, shared psychotic disorder, or a mood disorder (major depression or bipolar) with psychotic features.
• Persistence of psychotic symptoms due to nonadherence to antipsychotic medication.
• Medical contraindications to treatment with long-acting injectable risperidone.
• Serious neurological or endocrine disorder or medical condition /treatment known to affect the brain.
• A medical condition requiring medication with psychotropic effects.
• Clinical assessment that trial participation is contraindicated due to risk for homicidal or suicidal behavior.
• A diagnosis of diabetes (fasting glucose > 126 mg/dl).
• Requires with antidepressant or mood stabilizing medication.
• Previous treatment with a long acting formulation of an antipsychotic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: long-acting injectable risperidone; One week of oral risperidone dosage started at 2mg for the first day and then increased to 4mg. If no side effects are noted, participants are started on the long-acting risperidone. The usual dosage of long-acting risperidone in the study will be 25mg every 2 weeks for a total of 12 weeks. The medication will be administered intramuscularly via injection.

Drug: long-acting injectable risperidone; One week of oral risperidone dosage started at 2mg for the first day and then increased to 4mg. If no side effects are noted, participants are started on the long-acting risperidone. The usual dosage of long-acting risperidone in the study will be 25mg every 2 weeks for a total of 12 weeks. The medication will be administered intramuscularly via injection.; Other Names: Risperdal (oral) & Risperdal Consta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment Response Based Upon BPRS and CGI Ratings	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative Symptoms	Zero patients were analyzed as only one subject consented to the study and dropped out of the study before they were randomized. The negative symptoms that were going to be analyzed include: Affective Flattening, Alogia, Avolition /Apathy, and Anhedonia/Asociality	13 weeks

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: National Alliance for Research on Schizophrenia and Depression; The Zucker Hillside Hospital
• Investigators: Principal Investigator: Delbert G Robinson, M.D., The North Shore-Long Island Jewish Health System

Publications and helpful links

Helpful Links

• web site of NARSAD

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimate): April 13, 2006

Study Record Updates

• Last Update Posted (Actual): May 16, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: schizophrenia; risperidone; first episode
• Additional Relevant MeSH Terms: Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 05.04.161