Prospective Cytochrome P450 Genotyping and Clinical Outcomes in Patients With Psychosis

NCT01878513 | Completed

• 1 other identifier: 08-252B
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to examine whether determining treatment strategies based upon Cytochrome P450 2D6 (CYP2D6) genotype will improve drug response rates and clinical outcome in patients with psychosis. The investigators predict that prospectively testing CYP2D6 genotype and using this information to treat psychotic patients with risperidone will improve clinical outcomes. Specifically, CYP2D6 poor metabolizers who are treated with low dose and slow titration of risperidone will do better than those who are treated with usual dose and titration approach in terms of rates of side effects and clinical improvement.

Conditions

Schizophrenia; Schizoaffective Disorder; Psychotic Disorder Not Otherwise Specified; Severe Bipolar Disorder With Psychotic Features

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Scores on: 1. Schedule for Assessment of Negative Symptoms (SANS) 2. Brief Psychiatric Rating Scale (BPRS) 3. Global Impression - Improvement scale (CGI-I)

  6 weeks or discharge up to 6 weeks

Secondary Outcomes (1)

• Adverse Drug Effects

  6 weeks, discharge or discontinuation up to 6 weeks

Other Outcomes (2)

• Number of days before discontinuation

  6 weeks, discontinuation or discharge up to 6 weeks

• Days of Inpatient Stay

  6 weeks, discontinuation or discharge up to 6 weeks

Study Arms (3)

Low-dose-titration condition

EXPERIMENTAL

Poor and intermediate CYP2D6 metabolizers will be randomized to either low-dose-titration condition or treatment-as-usual condition. In the low-dose-titration condition, patients will be treated with risperidone 0.5mg bid for 5 days, then 1mg bid for 5 days, which may be increased to 1.5mg bid for another 5 days.

Drug: risperidone

Treatment-as-usual condition

EXPERIMENTAL

Poor and intermediate CYP2D6 metabolizers will be randomized to either low-dose-titration condition or treatment-as-usual condition. In the treatment-as-usual condition, patients will be treated with risperidone 1mg bid for 5 days, then 2mg bid for 5 days, which may be increased to 3mg bid for another 5 days.

Drug: risperidone

Open-label treatment-as-usual condition

EXPERIMENTAL

Extensive and ultrarapid CYP2D6 metabolizers will be treated open-label in the treatment-as-usual condition. Patients will be treated with risperidone 1mg bid for 5 days, then 2mg bid for 5 days, which may be increased to 3mg bid for another 5 days.

Drug: risperidone

Interventions

risperidone DRUG

3 levels of dosing dependent on which condition a patient is assigned to.

Also known as: Risperdal

Low-dose-titration condition; Open-label treatment-as-usual condition; Treatment-as-usual condition

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60;
• DSM-IV(Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder NOS (Not otherwise specified), bipolar disorder with psychotic features
• Having moderate to severe psychotic symptoms resulting in inpatient admission
• Able to provide informed consent

You may not qualify if:

• Evidence of serious medical conditions,
• Evidence of liver disease, as shown in elevated liver function test
• Female patients who are pregnant or breast feeding;
• History of allergic reactions to risperidone or Invega;
• History of risperidone or Invega treatment failure.
• History of receiving any long-acting injectable form of antipsychotic medications such as haloperidol decanoate, fluphenazine decanoate, Risperdal Consta, Invega Sustenna, and Zyprexa IntraMuscular in the past two months.
• History of treatment with clozapine.
• Medications that potentially interfere with the CYP450 2D9 enzyme family, including bupropion, fluoxetine, paroxetine, duloxetine, sertraline, cinacalcet, quinidine, terbinafine, amiodarone, and cimetidine, and as per clinical review by study physicians.
• Patients who are not able to provide informed consent due to impairment in decision-making capacity.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jianping Zhang, MD, PhD

  Zucker Hillside Hospital, Division of Psychiatry Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: June 17, 2013
• Study Start: September 23, 2009
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: August 27, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)