Recruiting

Anticholinergic Deprescription

Sponsor:

Deepak K. Sarpal, M.D.

Code:

NCT06562608

Conditions

Schizophrenia

Schizoaffective Disorder

Eligibility Criteria

Sex: All

Age: 40 - 70

Healthy Volunteers: Accepted

Interventions

Anticholinergic Deprescription

No Anticholinergic Deprescription

Study Details

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

Study ID

NCT06562608

Start date

Feb 1, 2025

Status verified date

Jul, 2026

Completion date

Jun 30, 2029

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70

Healthy Volunteers: Accepted

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.

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.

Study Design

Enrollment

105 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Anticholinergic Deprescription

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

active comparator: No Anticholinergic Deprescription

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

no intervention: Healthy Controls

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

Interventions

Anticholinergic Deprescription

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

No Anticholinergic Deprescription

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

Primary outcome measure

  • Change in cognitive performance [ Time Frame: 6 months ]
  • Change in scores on quality of life assessments. [ Time Frame: 6 months ]
  • Change in scores on functional outcome assessments. [ Time Frame: 6 months ]
  • change in brain functional connectivity. [ Time Frame: 6 months ]
  • change in activation of neurocognitive networks [ Time Frame: 6 months ]
  • Brain glutamate concentration [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Deepak K Sarpal, M.D.

4122465618sarpaldk@upmc.edu

Shaun M. Eack, Ph.D.

412.648.9029sme12@pitt.edu

Locations

UPMC Western Psychiatric Hospital/University of Pittsburgh

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contacts

Tori Blazinski

blazinskit2@upmc.edu

Principal Investigator:

Deepak K. Sarpal, M.D.

More Information

Sponsor

Deepak K. Sarpal, M.D.

Last update posted

Jul 10, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Deepak K. Sarpal, M.D. on 2026-07-10.