Escitalopram for Agitation in Alzheimer's Disease

NCT ID: NCT03108846

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-03
• Study Completion Date: 2025-05-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of escitalopram for agitation in Alzheimer's dementia.

Detailed Description

This study is designed to examine the efficacy and safety of escitalopram as treatment for agitation in Alzheimer's dementia (AD) patients. Participants with clinically significant agitation, and their caregiver(s), will receive a structured psychosocial intervention. Participants not showing a response three weeks later will be randomized 1:1 to escitalopram (up to 15 mg/day) or a matching placebo. Participants will receive study drug or placebo for 12 weeks, with in-person and remote (phone/video) visits at weeks 3, 6, 9, and 12, and with telephone contacts between in-person and remote visits. Participants who do show a response to the psychosocial intervention will not be randomized to study drug but will be followed remotely.

Conditions

Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Escitalopram

Escitalopram up to 15mg/day taken as 1-3 capsules each containing 5mg escitalopram once per day in the morning

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

5-15 mg/day (target: 15mg/day if tolerated)

Placebo

1-3 capsules each containing placebo only once per day in the morning

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Masked placebo

Interventions

Escitalopram

5-15 mg/day (target: 15mg/day if tolerated)

Intervention Type: DRUG

Placebo

Masked placebo

Intervention Type: DRUG

Other Intervention Names

Lexapro; non-applicable

Eligibility Criteria

Inclusion Criteria

1. Alzheimer's dementia diagnosed clinically by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (2011 NIA/AA criteria)

2. Mini-Mental State Examination Telephone (MMSET) score of 3-20 inclusive

3. Meets the International Psychogeriatric Association (IPA) provisional criteria for agitation in cognitive disorders

4. Clinically significant agitation/aggression as assessed by the Neuropsychiatric Inventory (NPI) for which either:

• The frequency is 'Very frequently,' or
• The frequency is 'Frequently' AND the severity is 'Moderate' or 'Marked'

5. Provision of informed consent for participation in the study by both caregiver and participant (or, if participant is unable to provide informed consent, with surrogate consent and participant assent)

6. Availability of a caregiver who spends at least several hours per week with the participant, supervises his/her care, is willing to accompany the participant to study visits, and is willing to participate in the study

7. Stable (for ≥ 7 days) dosing of antipsychotics for agitation or psychosis, if being used at all

8. A medication for agitation is appropriate, in the opinion of the study physician

Exclusion Criteria

1. Has major depression, as indicated by major depressive episode (MDE) in the past 90 days (meeting the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria)

2. Presence of another brain disease that fully explains the dementia, (e.g., extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis)

3. Residence in a skilled nursing or Long-Term Acute Care (LTAC) facility

4. Contraindication to treatment with escitalopram as determined by a study physician, such as recent (30 days) use of monoamine oxidase inhibitors (MAOIs) or potential participant is hypersensitive to escitalopram or citalopram or any inactive ingredients

5. Prior failed treatment attempt with citalopram or escitalopram for agitation after adequate trial, at minimally accepted dose

6. Indication for psychiatric hospitalization or acute suicidality, in the opinion of the study physician

7. Recent (< 7 days) changes in antipsychotics, anticonvulsants, or psychosis (delusions or hallucinations) requiring a new or change in antipsychotic treatment (in the opinion of the study physician)

8. Abnormal corrected QT interval using Bazett's formula (QTcB)** as determined on enrollment ECG (defined as > 450 ms for men and > 470 ms for women)

9. Recent (30 days) presence of severely reduced renal function (as identified by a Glomerular filtration rate (GFR) clearance < 30 mL/min) or reduced hepatic function

10. Current treatment (within 7 days) with any of the following:

• antidepressants (other than trazodone, ≤ 100 mg per day at bedtime)
• benzodiazepines (other than lorazepam), or
• psychostimulants

11. Recent (< 14 days) changes in Dextromethorphan/quinidine, prazosin, and pimavanserin

12. Recent (< 14 days) use of medical marijuana

13. Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes

14. Significant communicative impairments that would affect participation in a clinical trial

15. Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the potential participant to enroll in the trial

• if the QTcB is determined while the rhythm is paced, 50 ms is subtracted from the calculated value. The study cardiologist must confirm eligibility in this scenario.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 109 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

JHSPH Center for Clinical Trials

OTHER

Sponsor Role: lead

Responsible Party

Dave Shade

Director, S-CitAD Coordinating Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Constantine Lyketsos, MD, MHS

Role: STUDY_CHAIR

Johns Hopkins University

Locations

Banner Sun Health Research Institute

Sun City, Arizona, United States

Biomedical Research Foundation

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California Los Angeles/VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

University of Southern California Keck School of Medicine Memory and Aging Center

Los Angeles, California, United States

Miami Jewish Health Systems

Miami, Florida, United States

Kansas School of Medicine-Wichita Center for Clinical Research

Wichita, Kansas, United States

Maryland VA Health Care System

Baltimore, Maryland, United States

Johns Hopkins University School of Medicine, Bayview Medical Center

Baltimore, Maryland, United States

Alzheimer Disease Center

Quincy, Massachusetts, United States

Hackensack Meridian Health

Hackensack, New Jersey, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Ohio State University

Columbus, Ohio, United States

Abington Neurological Associates, Ltd

Abington, Pennsylvania, United States

Alzheimer Disease Research Center; University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Roper St. Francis Healthcare

Charleston, South Carolina, United States

Baylor AT&T Memory Center

Dallas, Texas, United States

UT Health San Antonio

San Antonio, Texas, United States

University of Virginia Adult Neurology

Charlottesville, Virginia, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

University of Calgary and Foothills Medical Centre

Calgary, Alberta, Canada

Lawson Health Research Institute/Parkwood Institute

London, Ontario, Canada

Neuropsychopharmacology Research Group, Sunnybrook

Toronto, Ontario, Canada

Unity Health

Toronto, Ontario, Canada

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Centre for Memory and Aging

Toronto, Ontario, Canada

Ontario Shores

Whitby, Ontario, Canada

Countries

United States; Canada

References

Rajji TK, Baksh SN, Shade DM, Ismail Z, Burhan AM, Okhravi HR, Padala PR, Rosenberg PB, Schneider LS, Porsteinsson AP, Lyketsos CG; S-CitAD Research Group. Escitalopram for agitation in Alzheimer's dementia: a randomized controlled phase 3 trial. Nat Med. 2025 May;31(5):1586-1591. doi: 10.1038/s41591-025-03569-y. Epub 2025 Mar 25.

Reference Type: DERIVED

PMID: 40133524 (View on PubMed)

Ehrhardt S, Porsteinsson AP, Munro CA, Rosenberg PB, Pollock BG, Devanand DP, Mintzer J, Rajji TK, Ismail Z, Schneider LS, Baksh SN, Drye LT, Avramopoulos D, Shade DM, Lyketsos CG; S-CitAD Research Group. Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial. Alzheimers Dement. 2019 Nov;15(11):1427-1436. doi: 10.1016/j.jalz.2019.06.4946. Epub 2019 Oct 3.

Reference Type: DERIVED

PMID: 31587995 (View on PubMed)

Other Identifiers

R01AG052510

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S-CitAD

Identifier Type: -

Identifier Source: org_study_id