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NCT Number: NCT06562608

Anticholinergic Deprescription in Schizophrenia

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

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Key information

Conditions

Schizophrenia Mental Disorders Psychotic Disorders Schizoaffective Disorder Schizophrenia Spectrum and Other Psychotic Disorders

Age range

40 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

UPMC Western Psychiatric Hospital/University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location status: Recruiting

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Primary DSM-defined diagnosis of schizophrenia, schizoaffective disorder, or unspecified psychotic disorder, verified by the Structured Clinical Interview for DSM-5 (SCID).
  • Prescription of benztropine or trihexyphenidyl for at least 6 months
  • Age 35-70 years.
  • ACBS score >= 3.
  • Mild or absent extrapyramidal symptoms (Determined by clinical pharmacists and prescribers).
  • Competency and willingness to sign informed consent.

Inclusion criteria

for the healthy control group:

  • Age 40-70 years.
  • Competency and willingness to sign informed consent.

Exclusion criteria

  • 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.

Exclusion criteria

for Healthy Control (HC) subjects:

  • 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.

Treatment and study plan

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.

No Anticholinergic Deprescription

Drug

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

Primary outcomes

  1. Change in cognitive performance

    Time frame: 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.

  2. Change in scores on quality of life assessments.

    Time frame: 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.

  3. Change in scores on functional outcome assessments.

    Time frame: 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.

  4. change in brain functional connectivity.

    Time frame: 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.

  5. change in activation of neurocognitive networks

    Time frame: 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.

  6. Brain glutamate concentration

    Time frame: 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.

Interested in participating?

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Interested in participating?

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Sponsors and collaborators

Lead sponsor

Deepak K. Sarpal, M.D.

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Neural Mechanisms of Anticholinergic Burden in Mid- to Late-Life Schizophrenia Spectrum

Important dates

Study start
2025
Primary completion
2028
Study completion
2029
First posted
Aug 20, 2024
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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