Minimizing Doses of Antipsychotic Medication in Older Patients With Schizophrenia.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00716755
Recruitment Status : Completed
First Posted : July 16, 2008
Last Update Posted : February 26, 2016
Information provided by (Responsible Party):
Ariel Graff, Centre for Addiction and Mental Health

Brief Summary:
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 or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Schizophreniform Disorder Delusional Disorder Psychotic Disorder Drug: Risperidone/Olanzapine and PET scans Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Minimal Effective Dose of Antipsychotic Medication in Older Patients With Schizophrenia: a PET Study.
Study Start Date : October 2009
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Dose Reduction
See Intervention
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.

Primary Outcome Measures :
  1. Occupancy of risperidone/olanzapine at the dopamine D2 receptor [ Time Frame: intermittently ]

Secondary Outcome Measures :
  1. Tolerability of 40 % antipsychotic dose reduction and its relation to the % change in occupancy following dose reduction [ Time Frame: intermittent ]
  2. 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 ]

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 or Risperdal Consta within 12 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00716755

Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
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

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Ariel Graff, MD, PhD, Centre for Addiction and Mental Health Identifier: NCT00716755     History of Changes
Other Study ID Numbers: 156/2007
First Posted: July 16, 2008    Key Record Dates
Last Update Posted: February 26, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Ariel Graff, Centre for Addiction and Mental Health:
Positron emission tomography
D2 receptor
schizoaffective disorder
schizophreniform disorder
delusional disorder
psychotic disorder NOS

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia, Paranoid
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Behavioral Symptoms
Antipsychotic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators