Clinical trial NCT06562608: Anticholinergic Deprescription in Schizophrenia
Official title: Neural Mechanisms of Anticholinergic Burden in Mid- to Late-Life Schizophrenia Spectrum
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2024-08-20
Enrollment: 105
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change in cognitive performance
timeFrame: 6 months
measure: Change in scores on quality of life assessments.
timeFrame: 6 months
measure: Change in scores on functional outcome assessments.
timeFrame: 6 months
measure: change in brain functional connectivity.
timeFrame: 6 months
measure: change in activation of neurocognitive networks
timeFrame: 6 months
measure: Brain glutamate concentration
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Hospital/University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Deepak K Sarpal, M.D.
role: PRINCIPAL_INVESTIGATOR
References: