This site became the new on June 19th. Learn more.
Show more Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu
Give us feedback

Minimizing Doses of Antipsychotic Medication in Older Patients With Schizophrenia.

This study has been completed.
Information provided by (Responsible Party):
Ariel Graff, Centre for Addiction and Mental Health Identifier:
First received: July 14, 2008
Last updated: February 25, 2016
Last verified: February 2016
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: None (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:

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

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

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

Enrollment: 45
Study Start Date: October 2009
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description


Ages Eligible for Study:   50 Years and older   (Adult, Senior)
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.
  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 identifier: 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
  More Information

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
Study First Received: July 14, 2008
Last Updated: February 25, 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 processed this record on September 21, 2017