Anticholinergic Deprescription in Schizophrenia

Deepak K. Sarpal, M.D.

Status and phase: Enrolling; Phase 4

Conditions: Schizophrenia; Schizoaffective Disorder

Treatments: Drug: Anticholinergic Deprescription; Drug: No Anticholinergic Deprescription

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06562608

STUDY24050090

R01MH135096 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Enrollment: 105 estimated patients

Sex: All

Ages: 40 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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105 participants in 3 patient groups

Anticholinergic Deprescription

Experimental group

Description:

In this arm, clinically determined unneeded benztropine or trihexyphenidyl will be deprescribed, per routine care by clinical providers.

Treatment:

Drug: Anticholinergic Deprescription

No Anticholinergic Deprescription

Active Comparator group

Description:

In this arm, no deprescription of benztropine or trihexyphenidyl will occur.

Treatment:

Drug: No Anticholinergic Deprescription

Healthy Controls

No Intervention group

Description:

In this arm, a healthy control group with minimal anticholinergic burden will be examined longitudinally.