Minimizing Doses of Antipsychotic Medication in Older Patients With Schizophrenia.
This study is currently recruiting participants.
Verified January 2013 by Centre for Addiction and Mental Health
Sponsor:
Centre for Addiction and Mental Health
Information provided by (Responsible Party):
Ariel Graff, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT00716755
First received: July 14, 2008
Last updated: January 23, 2013
Last verified: January 2013
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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
Olanzapine pamoate
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.
|
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 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
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:
No publications provided
| Responsible Party: | Ariel Graff, MD, PhD, 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: | January 23, 2013 |
| Health Authority: | Canada: Health Canada |
Keywords provided by Centre for Addiction and Mental Health:
|
schizophrenia Positron emission tomography antipsychotics risperidone olanzapine Dopamine |
D2 receptor elderly schizoaffective disorder schizophreniform disorder delusional disorder psychotic disorder NOS |
Additional relevant MeSH terms:
|
Schizophrenia, Paranoid Schizophrenia Schizophrenia and Disorders with Psychotic Features Delusions Psychotic Disorders Mental Disorders 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 May 19, 2013