Anticholinergic Deprescription in Schizophrenia

Phase 4RecruitingNCT06562608

Deepak K. Sarpal, M.D.105 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

105

Conditions

Schizophrenia Schizoaffective Disorder

Interventions

Eligibility

Sex: ALLMin age: 40 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Primary DSM-defined diagnosis of schizophrenia or schizoaffective disorder verified by the Structured Clinical Interview for DSM-5 (SCID). 2. Prescription of benztropine or trihexyphenidyl for at least 6 months 3. Age 40-70 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. Exclusion criteria for Healthy Control (HC) subjects: 1. No history of psychotic illness and no active Axis I disorder as determined by clinical interview using the SCID-NP. 2. Score greater than 1 on the ACB scale. 3. MR imaging contraindications. 4. Neurologic conditions, any serious non-psychiatric disorder that could affect brain functioning, or intellectual disability. 5. HC with family history of psychosis will be excluded, as such individuals show subtle, but significant cognitive and neurobiological abnormalities. 6. Individuals currently taking anticholinergic medications for reasons other than SSD.

Outcomes

Primary Outcomes

Change in cognitive performance

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.

Time frame: 6 months

Change in scores on quality of life assessments.

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.

Time frame: 6 months

Change in scores on functional outcome assessments.

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.

Time frame: 6 months

change in brain functional connectivity.

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.

Time frame: 6 months

change in activation of neurocognitive networks

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.

Time frame: 6 months

Brain glutamate concentration

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.

Time frame: 6 months

Anticholinergic Deprescription in Schizophrenia

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts