SSRI's and the Rate of Progression From MCI to Dementia

Impact of SSRIs on the Rate of Progression of Patients With Mild Cognitive Impairment to Alzheimer's Disease Dementia and Other Neurodegenerative Dementias, With or Without Concurrent Use of Acetylcholinesterase Inhibitors

This trial is investigating if serotonin reuptake inhibitor (SSRI) use in Mild Cognitive Impairment (MCI) patients will lead to a lower rate of progression to dementia.

It's hypothesized that patients treated with an SSRI at the time of MCI diagnosis, without evidence of an active primary psychiatric condition other than neurocognitive disorder, will have a lower rate of progression to Alzheimer's disease dementia or to other types of dementia.

Study Overview

• Status: Withdrawn
• Conditions: Dementia; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Drug: SSRI

Detailed Description

Whether SSRIs affect the progression of MCI to dementia is not well studied with longitudinal prospectively collected date. Any decrease in the incidence of the progression of MCI to Alzheimer's dementia would be beneficial to patients.

This trial is investigating if serotonin reuptake inhibitor (SSRI) use in Mild Cognitive Impairment (MCI) patients will lead to a lower rate of progression to dementia.

This is a retrospective study of prospectively collected longitudinal data in patients followed at the Cognitive and Memory Disorders Center from 2010-2019. There are 3 arms: (1) subjects with an initial diagnosis of MCI who were treated with an SSRI for at least one year prior to the diagnosis of MCI (2) subjects with an initial diagnosis of MCI who were started on an SSRI at the time of diagnosis and treated with it for at least 6 months after the diagnosis of MCI and (3) subjects without SSRI use.

All the subjects have been evaluated based on a comprehensive standardized evaluation for the initial diagnosis and follow up over time. Chart reviews will be conducted on newly diagnosed MCI patients from 2010-2016 who have at least 2 years of annual follow up documented in their electronic medical record. Follow up visit notes through 2019 will be included in the review.

• Study Type: Observational

Contacts and Locations

• Study Contact: Name: Jennifer Icenhour; Phone Number: 614-293-6882; Email: jennifer.icenhour@osumc.edu
• Study Contact Backup: Name: Nicole Vrettos, MS; Phone Number: 614-366-8642; Email: nicole.vrettos@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Subjects who meet the inclusion/exclusion criteria at the time of the initial diagnosis will be included in the review.

Description

Inclusion Criteria:

1. Age 55+
2. Diagnosis of mild cognitive impairment.
3. One year treatment with an SSRI prior to diagnosis of MCI or six months treatment after diagnosis of MCI for the intervention groups. No treatment with an SSRI prior to the diagnosis of MCI or after the diagnosis of MCI for the control group.
4. A minimum of two annual follow up evaluations.

Exclusion Criteria:

1. Patients with CNS infection or inflammation
2. HIV
3. Syphilis
4. Patients with poorly controlled Epilepsy based on the opinion of the investigator.
5. Patients with space occupying lesions of the brain (glioma, meningioma, brain metastasis).
6. Patients with systemic inflammatory condition or cancer undergoing chemotherapy or on chronic immune modulatory treatments.
7. Blind patients that were not able to complete a cognitive assessment.
8. Patients with chronic pain who are on excluded pain medications.
9. Patients with Attention Deficit Disorder that require the use of stimulant medications.
10. Patients with Traumatic Brain Injury.
11. Patients with Cerebral Aneurysm Rupture.
12. Patients with chronic psychiatric conditions, unless in remission. Recurrent chronic psychiatric condition in relapse, chronic recurrent Major Depression in relapse, chronic recurrent bipolar disorder, chronic relapsing schizoaffective disorder and chronic recurrent anxiety disorder requiring chronic use of benzodiazepines are exclusionary.
13. Patients taking an excluded medication.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SSRI for at least one year prior to the diagnosis of MCI; subjects with an initial diagnosis of MCI who were treated with an SSRI for at least one year prior to the diagnosis of MCI	Drug: SSRI; Selective serotonin reuptake inhibitor; Other Names: Selective serotonin reuptake inhibitor
SSRI at the time of diagnosis and treated with it for at least 6 months after the diagnosis of MCI	Drug: SSRI; Selective serotonin reuptake inhibitor; Other Names: Selective serotonin reuptake inhibitor
Subjects without SSRI use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSRI rate of progression to dementia	1.To determine if subjects treated with an SSRI for at least one year prior to the diagnosis of MCI or at least 6 months after the diagnosis of MCI will (a) have a lower rate of progression to Alzheimer's disease dementia or (b) have a lower rate of progression to other dementia conditions (i.e. Lewy Body Dementia, Frontotemporal Dementia, Vascular Dementia, Normal Pressure Hydrocephalus, Parkinson Disease Dementia… etc) compared to subjects who are not treated with an SSRI.	2010-2019
SSRI and acetylcholinesterase inhibitor use progression to dementia	2.To determine if SSRI use in combination with acetylcholinesterase inhibitor use will affect the rate of progression to dementia.	2010-2019

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of conversion from MCI to dementia and the other factors	1. To investigate correlations between the rate of conversion from MCI to dementia and other factors.	2010-2019

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Maria Kataki, MD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): October 6, 2023
• Study Completion (Actual): October 6, 2023

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: SSRI
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Cognition Disorders; Dementia; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Receptor Agonists; Serotonin; Selective Serotonin Reuptake Inhibitors
• Other Study ID Numbers: 2020H0375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No