Antipsychotic Polypharmacy in Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Canadian Psychiatric Research Foundation
Information provided by:
Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT00493233
First received: June 4, 2007
Last updated: May 18, 2009
Last verified: May 2009
  Purpose

The literature suggests that when a patient is prescribed more than one antipsychotic for at least 30 days, he or she is likely to continue on that combination. In this 12 week study 100 adult patients being treated on more than one antipsychotic medication for at least 30 days will be recruited. In order to control for the natural course of the illness, patients will be randomly assigned to one of two groups: the first group will continue the second medication hidden in a capsule at the same dose, while the second group will be given an inactive capsule (placebo) - the capsules in both group will be identical such that neither the patient nor the treating doctor will be able to identify the group assignment.


Condition Intervention
Schizophrenia
Drug: 2 antipsychotic medications (combinations of olanzapine, risperidone, clozapine, seroquel, haldol, perphenazine)
Drug: main antipsychotic medication and placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Antipsychotic Polypharmacy in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Brief Psychiatric Rating Scale (BPRS) [ Time Frame: intermittent ] [ Designated as safety issue: No ]
  • Clinical Global Impression Scale [ Time Frame: intermittent ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Barned Akathisia Scale [ Time Frame: intermittent ] [ Designated as safety issue: No ]
  • Simpson-Angus Scale (SAS) [ Time Frame: intermittent ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: November 2006
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: 2 antipsychotic medications (combinations of olanzapine, risperidone, clozapine, seroquel, haldol, perphenazine)
Primary antipsychotic medication (olanzapine, oral risperidone, seroquel, clozapine, haldol, perphenazine) will be determined by the treating physician and participants will continue taking the concomitant antipsychotic drug. The dose of the main antipsychotic drug will remain open and flexible at the discretion of the attending physician. The dose of the "second" antipsychotic drug will remain fixed throughout the study period.
Placebo Comparator: 2 Drug: main antipsychotic medication and placebo
The "main" antipsychotic drug will be determined by the treating physician. Participants will be allocated to placebo in place of the concomitant antipsychotic drug. The dose of the "main" antipsychotic drug will remain open and flexible at the discretion of the attending physician.

Detailed Description:

There is no evidence that using more than one antipsychotic drug enhances clinical efficacy. Nonetheless, this practice is highly prevalent (up to 1/3 of our patient population), and physicians are reluctant to reduce patients' treatment to a single antipsychotic drug for fear of precipitating relapse. This study therefore seeks to evaluate the effectiveness of continued treatment with more than one antipsychotic drug using a rigorous placebo-controlled design. The results of this study will subsequently serve to guide physicians in making appropriately informed decisions regarding the continuation of multiple antipsychotic drugs.

Our primary hypothesis is that we expect to find no difference in the primary variable of interest (BPRS) following reduction to antipsychotic monotherapy (placebo group) versus continuing antipsychotic polypharmacy.

This proposed study is the first study to systematically address the reduction of antipsychotic polypharmacy to monotherapy in patients with primary psychotic disorders in a prospective, double-blind, placebo-controlled design. The results of this study will have important implications for the clinical practice of physicians treating the severely mentally ill who are often constrained to practice beyond the limits of available clinical guidelines and evidence based medicine. Thus, in light of the high and growing prevalence of this practice, the proposed study speaks to a real and practical clinical dilemma within this field. Furthermore, as a university-based, tertiary care psychiatric centre serving thousands of severely ill patients suffering from primary psychotic disorders and with an established track record for innovative clinical research, we are uniquely placed to address these critical questions.

Male or female subjects aged ≥ 18 years suffering from a primary psychotic disorder treated with two antipsychotic drugs for at least 30 days (excluding "prn" or "as needed" antipsychotic prescriptions) will be eligible to participate in this study. Subjects with a history of treatment with a depot antipsychotic within 6-months of enrollment will be excluded form the study unless the depot antipsychotic is considered the "main" antipsychotic drug in this study. The "main" antipsychotic drug will be determined by the treating physician, except for the case of clozapine which will be considered the 'main' antipsychotic. Eligible subjects will be randomly allocated to two groups: Group 1 will continue taking the concomitant antipsychotic drug; Group 2 will be allocated to placebo in place of the concomitant antipsychotic drug. The dose of the "main" antipsychotic drug will remain open and flexible at the discretion of the attending physician. The dose of the "second" antipsychotic drug will remain fixed throughout the study period.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged ≥ 18 years
  • Suffering from a primary psychotic disorder (confirmed using the MINI International Neuropsychiatric Interview for DSM-IV (Version 5.0.0)
  • Treated with two antipsychotic drugs for at least 30 days (excluding "prn" or "as needed" antipsychotic prescriptions)

Exclusion Criteria:

  • A history of treatment with a depot antipsychotic within 6-months of enrollment will be excluded form the study unless the depot antipsychotic is considered the "main" antipsychotic drug in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493233

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Canadian Psychiatric Research Foundation
Investigators
Principal Investigator: David Mamo, MD, MSc Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. David Mamo, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT00493233     History of Changes
Other Study ID Numbers: 174/2006
Study First Received: June 4, 2007
Last Updated: May 18, 2009
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
schizophrenia
antipsychotics
polypharmacy
double-blind
randomized

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Risperidone
Haloperidol
Perphenazine
Antipsychotic Agents
Quetiapine
Olanzapine
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Antagonists
Dopamine Agents
Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on July 24, 2014