Minimizing Doses of Antipsychotic Medication in Older Patients With Schizophrenia.

NCT00716755 | Completed DMC

• 1 other identifier: 156/2007
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Delusional Disorder; Psychotic Disorder

Keywords

Positron emission tomography; antipsychotics; risperidone; olanzapine; Dopamine; D2 receptor; elderly; schizophrenia; schizoaffective disorder; schizophreniform disorder; delusional disorder; psychotic disorder NOS

Outcome Measures

Primary Outcomes (1)

• Occupancy of risperidone/olanzapine at the dopamine D2 receptor

  PET scan data showing how much dopamine D2 receptors are occupied

  intermittently

Secondary Outcomes (2)

• Tolerability of 40 % antipsychotic dose reduction and its relation to the % change in occupancy following dose reduction

  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.

  intermittent

Study Arms (1)

Dose Reduction

EXPERIMENTAL

See Intervention

Drug: Risperidone/Olanzapine and PET scans

Interventions

Risperidone/Olanzapine and PET scans DRUG

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.

Also known as: Risperidal, Zyprexa

Dose Reduction

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (2)

• Iwata Y, Nakajima S, Caravaggio F, Suzuki T, Uchida H, Plitman E, Chung JK, Mar W, Gerretsen P, Pollock BG, Mulsant BH, Rajji TK, Mamo DC, Graff-Guerrero A. Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia. J Clin Psychiatry. 2016 Dec;77(12):e1557-e1563. doi: 10.4088/JCP.15m10538.

  PMID: 28086010 DERIVED

• Fervaha G, Caravaggio F, Mamo DC, Mulsant BH, Pollock BG, Nakajima S, Gerretsen P, Rajji TK, Mar W, Iwata Y, Plitman E, Chung JK, Remington G, Graff-Guerrero A. Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study. Psychopharmacology (Berl). 2016 Oct;233(21-22):3803-3813. doi: 10.1007/s00213-016-4415-6. Epub 2016 Aug 24.

  PMID: 27557949 DERIVED

Related Links

• 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.

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Schizophrenia, Paranoid; Mental Disorders

Interventions

Risperidone; Olanzapine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• David C. Mamo, MD MSc

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

• Ariel Graff-Guerrero, MD,PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 14, 2008
• First Posted: July 16, 2008
• Study Start: October 1, 2009
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)