Minimizing Doses of Antipsychotic Medication in Older Patients With Schizophrenia. - Full Text View

Sponsor:	Centre for Addiction and Mental Health
Information provided by (Responsible Party):	Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:	NCT00716755

Purpose

Since side effects of antipsychotics, dopamine D2 receptor blockers, frequently occur in older patients with schizophrenia and the risk is dose dependent, clinical guidelines universally advocate the use of lower doses. However, there is no report to test this dosing guideline with measurements of D2 receptor blockade caused by antipsychotics. In this study, dopamine D2 receptor occupancy will be measured, using Positron Emission Tomography (PET), in 40 patients aged 50 and older with schizophrenia-spectrum disorders before and after a gradual 40 % dose reduction of antipsychotics that was safely achieved in the past study while setting a target dose still above the lower limit of the dose range recommended in clinical guidelines for older patients. Our goal is to relate changes in clinical outcome, including subjective and objective clinical ratings, to dopamine D2 receptor occupancy, and compare these results with the data for younger patients in the literature.

Condition	Intervention
Schizophrenia Schizoaffective Disorder Schizophreniform Disorder Delusional Disorder Psychotic Disorder	Drug: Risperidone/Olanzapine and PET scans

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Minimal Effective Dose of Antipsychotic Medication in Older Patients With Schizophrenia: a PET Study.

Resource links provided by NLM:

MedlinePlus related topics: Mental Disorders Mental Health Nuclear Scans Psychotic Disorders Schizophrenia

Drug Information available for: Dopamine Dopamine hydrochloride Risperidone Olanzapine

U.S. FDA Resources

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

Primary Outcome Measures:

Occupancy of risperidone/olanzapine at the dopamine D2 receptor [ Time Frame: intermittently ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tolerability of 40 % antipsychotic dose reduction and its relation to the % change in occupancy following dose reduction [ Time Frame: intermittent ] [ Designated as safety issue: No ]
Relationship between plasma concentration of risperidone and its active metabolite, 9-OH-risperidone(or olanzapine) and dopamine D2 receptor occupancy in older patients, in comparison to historic young controls. [ Time Frame: intermittent ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	October 2009
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: Risperidone/Olanzapine and PET scans Current risperidone/olanzapine users who are 50 or older will be recruited. Dopamine D2 dopamine receptors using a selective D2 dopamine receptor ligand, [11C]-raclopride, and plasma levels of risperidone and 9-OH-risperidone, or of olanzapine, and prolactin will be measured on the 1st PET visit. Subsequently, there will be gradual dose reductions of risperidone or olanzapine by 0.5 and 2.5 mg per week, respectively (as long as the total reduction does not exceed 40%). At least 5 days after the termination of the dose taper, participants will have the second PET scan. Participants will be followed up for 24 weeks after the termination of the dose reduction.

Arms

Assigned Interventions

Experimental: 1

Drug: Risperidone/Olanzapine and PET scans

Current risperidone/olanzapine users who are 50 or older will be recruited. Dopamine D2 dopamine receptors using a selective D2 dopamine receptor ligand, [11C]-raclopride, and plasma levels of risperidone and 9-OH-risperidone, or of olanzapine, and prolactin will be measured on the 1st PET visit. Subsequently, there will be gradual dose reductions of risperidone or olanzapine by 0.5 and 2.5 mg per week, respectively (as long as the total reduction does not exceed 40%). At least 5 days after the termination of the dose taper, participants will have the second PET scan. Participants will be followed up for 24 weeks after the termination of the dose reduction.

Show Detailed Description

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age of 50 and older
DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or psychotic disorder NOS
Having been treated with oral risperidone at a steady dose of ≥ 2 mg/day, or with olanzapine at a steady dose of ≥10 mg/day, for at least 12 months.

Exclusion Criteria:

Incapacity to provide consent to psychiatric treatment
Participation in this study would result in exceeding the annual radiation dose limits (20 mSv) for human subjects participating in research studies.
Substance abuse or dependence (within past six months)
Positive urine drug screen
Positive serum pregnancy test at screening or positive urine pregnancy test before PET scan
Having taken more than one dose of antipsychotics other than risperidone or olanzapine during the 7 days preceding the PET scan
History of treatment with long-acting (depot) neuroleptic antipsychotic medication within 6 months or Risperdal Consta within 4 months of PET scanning
Metal implants or a pace-maker that would preclude the MRI scan
Addition of or change in dose of antidepressants, valproic acid, lithium, carbamazepine, or lamotrigine for mental health reasons within 12 months of screening
History of head trauma resulting in loss of consciousness > 30 minutes that required medical attention
Unstable physical illness or significant neurological disorder including a seizure disorder
Size of head, neck, and body being unable to fit PET and MRI scanners
Refusal to give consent to investigator to communicate with physician of record for the entire duration of the study
Psychiatric concerns raised by the physician of record regarding participation in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00716755

Contacts

Contact: Ariel Graff-Guerrero, MD, PhD

416-535-8501 ext 4834

ariel_graff@camh.net

Locations

Canada, Ontario
Centre for Addiction and Mental Health	Recruiting
Toronto, Ontario, Canada, M5T 1R8
Sub-Investigator: Benoit Mulsant, MD
Sub-Investigator: Bruce Pollock, MD PhD
Sub-Investigator: Shinichiro Nakajima, MD, PhD

Sponsors and Collaborators

Centre for Addiction and Mental Health

Investigators

Principal Investigator:	David C. Mamo, MD MSc	Centre for Addiction and Mental Health
Principal Investigator:	Ariel Graff-Guerrero, MD,PhD	Centre for Addiction and Mental Health

More Information

Additional Information:

Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating Centre. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:	NCT00716755 History of Changes
Other Study ID Numbers:	156/2007
Study First Received:	July 14, 2008
Last Updated:	October 7, 2011
Health Authority:	Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:

Positron emission tomography
antipsychotics
risperidone
olanzapine
Dopamine
D2 receptor

elderly
schizophrenia
schizoaffective disorder
schizophreniform disorder
delusional disorder
psychotic disorder NOS

Additional relevant MeSH terms:

Schizophrenia, Paranoid
Delusions
Psychotic Disorders
Mental Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Behavioral Symptoms
Antipsychotic Agents
Risperidone
Olanzapine
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents

Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 12, 2012