Anticholinergic Deprescription in Schizophrenia

NCT06562608 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: STUDY24050090R01MH135096
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  6 months

Study Arms (3)

Anticholinergic Deprescription

EXPERIMENTAL

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

Drug: Anticholinergic Deprescription

No Anticholinergic Deprescription

ACTIVE COMPARATOR

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

Drug: No Anticholinergic Deprescription

Healthy Controls

NO INTERVENTION

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

Interventions

Anticholinergic Deprescription DRUG

per routine clinical care, people in the active arm of the study will undergo deprescription of benztropine or trihexyphenidyl per routine clinical care.

Anticholinergic Deprescription

No Anticholinergic Deprescription DRUG

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

No Anticholinergic Deprescription

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary DSM-defined diagnosis of schizophrenia or schizoaffective disorder verified by the Structured Clinical Interview for DSM-5 (SCID).
• Prescription of benztropine or trihexyphenidyl for at least 6 months
• Age 40-70 years.
• ACBS score \>= 3.
• Mild or absent extrapyramidal symptoms (Determined by clinical pharmacists and prescribers).
• Competency and willingness to sign informed consent.
• Age 40-70 years.
• Competency and willingness to sign informed consent.

You may not qualify if:

• Serious anticholinergic side-effects (e.g., fever, blurred vision) indicative of a need for immediate removal of anticholinergics,
• 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).
• Significant risk of suicidal or homicidal behavior.
• Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent.
• Contraindications for MR imaging (e.g., a pacemaker).
• 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.
• Patients concurrently treated with electroconvulsive therapy will be excluded because of its effects on cognition.
• No history of psychotic illness and no active Axis I disorder as determined by clinical interview using the SCID-NP.
• Score greater than 1 on the ACB scale.
• MR imaging contraindications.
• Neurologic conditions, any serious non-psychiatric disorder that could affect brain functioning, or intellectual disability.
• HC with family history of psychosis will be excluded, as such individuals show subtle, but significant cognitive and neurobiological abnormalities.
• Individuals currently taking anticholinergic medications for reasons other than SSD.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• Deepak K. Sarpal, M.D.: lead

Study Sites (1)

UPMC Western Psychiatric Hospital/University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Deepak K Sarpal, M.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deepak K Sarpal, M.D.

CONTACT

4122465618; sarpaldk@upmc.edu

Shaun M. Eack, Ph.D.

CONTACT

412.648.9029; sme12@pitt.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 16, 2024
• First Posted: August 20, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR, ANALYTIC CODE

Locations

US (1)