Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
In this study, the investigators will examine whether a deprescription of unnecessary anticholinergic drugs (benztropine or trihexyphenidyl) can augment quality of life, functioning, and neurocognition in individuals who with schizophrenia. Individuals identified by clinical services who have unneeded prescriptions benztropine or trihexyphenidyl will be eligible for deprescription and study entry. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will will be randomized to either staying on their anticholinergic drugs or undergoing deprescription per routine clinical care, and will undergo follow-up evaluations across 6 months. The investigators predict that reducing and deprescribing these drug, if clinically determined to be unnecessary will will enhance functioning, neurocognition
Interventions
DRUGAnticholinergic Deprescription
per routine clinical care, people in the active arm of the study will undergo deprescription of benztropine or trihexyphenidyl per routine clinical care.
DRUGNo Anticholinergic Deprescription
In this arm, no deprescription of benztropine or trihexyphenidyl will occur.
Sponsors
Deepak K. Sarpal, M.D.
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Primary DSM-defined diagnosis of schizophrenia, schizoaffective disorder, or unspecified psychotic disorder, verified by the Structured Clinical Interview for DSM-5 (SCID). 2. Prescription of benztropine or trihexyphenidyl for at least 6 months 3. Age 35-70 years. 4. ACBS score \>= 3. 5. Mild or absent extrapyramidal symptoms (Determined by clinical pharmacists and prescribers). 6. Competency and willingness to sign informed consent. Inclusion criteria for the healthy control group: 1. Age 40-70 years. 2. Competency and willingness to sign informed consent.
Exclusion criteria
1. Serious anticholinergic side-effects (e.g., fever, blurred vision) indicative of a need for immediate removal of anticholinergics, 2. Serious neurologic or medical condition/treatment that impacts the brain and Neurodegenerative conditions such as Parkinson's, dementia, etc.; autoimmune conditions such as Multiple Sclerosis (MS) and lupus; as well as traumatic brain injury (TBI). 3. Significant risk of suicidal or homicidal behavior. 4. Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent. 5. Contraindications for MR imaging (e.g., a pacemaker). 6. Current SCID-verified substance use disorder will be excluded to avoid the confounding impact of significant substance use comorbidity. Participants with a history of substance use disorder that is in early or full remission will be eligible, to enhance generalizability. 7. Patients concurrently treated with electroconvulsive therapy will be excluded because of its effects on cognition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive performance | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in cognitive performance via scores from the MATRICS Consensus Cognitive Battery. |
| Change in scores on quality of life assessments. | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in quality of life, measured with the WHOQOL-BREF. |
| Change in scores on functional outcome assessments. | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in functional outcomes, measured with the Specific Level of Functioning Scale. |
| change in brain functional connectivity. | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain functional connectivity between the basal forebrain and linked structures, such as regions of the cognitive control network, and the globus pallidus. |
| change in activation of neurocognitive networks | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain activation of the cognitive control network via the AX-CPT, and activation of the hippocampus during memory encoding/retrieval via the Relational and Item-Specific Encoding task. |
| Brain glutamate concentration | 6 months | We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain glutamate concentrations in the hippocampus and the dorsal anterior cingulate cortex. |
Countries
United States
Contacts
CONTACTDeepak K Sarpal, M.D.
CONTACTShaun M. Eack, Ph.D.
PRINCIPAL_INVESTIGATORDeepak K Sarpal, M.D.
University of Pittsburgh
Outcome results
None listed