Escitalopram for Agitation in Alzheimer's Disease

(S-CitAD Trial)

Not currently recruiting at 34 trial locations

Overseen By Douglas Scharre, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: JHSPH Center for Clinical Trials

Must be taking: Antipsychotics

Must not be taking: Antidepressants, Benzodiazepines, Psychostimulants

Disqualifiers: Major depression, Other brain diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether escitalopram can safely and effectively reduce agitation in people with Alzheimer's disease. Participants will receive either escitalopram or a placebo (a pill with no active drug) once daily. The trial seeks individuals diagnosed with Alzheimer's who frequently experience noticeable agitation or aggression. Those who have previously tried escitalopram or citalopram without success or have conditions like major depression or other brain diseases are not eligible. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications to join the trial. If you're taking antidepressants (except trazodone at a low dose), benzodiazepines (except lorazepam), or psychostimulants, you must stop them at least 7 days before starting. Recent changes in some other medications like Dextromethorphan/quinidine, prazosin, and pimavanserin also require a 14-day gap.

Is there any evidence suggesting that escitalopram is likely to be safe for humans?

Research has shown that escitalopram is generally safe for treating agitation in Alzheimer's patients. Although it may not significantly reduce agitation, it is usually well-tolerated. However, the risk of more frequent falls should be considered. Regarding side effects, escitalopram is considered safe, especially compared to citalopram, which can affect cognition and heart health. Overall, current evidence suggests that escitalopram is safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for agitation in Alzheimer's Disease, such as antipsychotics and benzodiazepines, escitalopram is an SSRI that targets serotonin levels in the brain. This selective serotonin reuptake inhibitor is believed to offer a more favorable side effect profile compared to antipsychotics, which can carry risks like sedation and increased mortality in elderly patients. Researchers are excited about escitalopram because it may reduce agitation without the heavy sedation or cognitive dulling associated with other medications, potentially improving the quality of life for patients and their caregivers.

What evidence suggests that escitalopram might be an effective treatment for agitation in Alzheimer's?

This trial will compare escitalopram with a placebo to treat agitation in Alzheimer's disease. Research has shown mixed results for using escitalopram, a common depression medication, in this context. Some studies found that a similar drug, citalopram, helped 40% of patients improve, compared to 26% who took a placebo (a pill with no active medicine). However, other studies indicated that escitalopram did not significantly reduce agitation, with about 30% of patients improving whether they took escitalopram or a placebo. While escitalopram is usually well tolerated, concerns exist about increased risks like falls. Overall, although escitalopram is related to citalopram, evidence for its effectiveness in treating agitation in Alzheimer's disease remains unclear. ^{1 2 3 4 6}

Who Is on the Research Team?

Constantine Lyketsos, MD, MHS

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's dementia experiencing frequent and severe agitation/aggression. Participants must be diagnosed by NIA/AA criteria, have a caregiver, and if using antipsychotics, the dosage should be stable. Excluded are those with major depression recently, residing in certain care facilities, recent medication changes that affect the brain or heart function issues.

Inclusion Criteria

You have frequent and moderate to severe agitation or aggression based on a specific assessment.

You scored between 3 and 20 on the Mini-Mental State Examination Telephone (MMSET).

I have a caregiver willing to support me during the study.

Exclusion Criteria

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

You have been recently hospitalized for a mental health condition or are currently having strong thoughts of harming yourself, according to the study doctor's opinion.

I am not currently taking certain antidepressants, benzodiazepines, or psychostimulants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Psychosocial Intervention

Participants and their caregivers receive a structured psychosocial intervention

3 weeks

1 visit (in-person)

Treatment

Participants receive escitalopram or placebo for 12 weeks

12 weeks

4 visits (in-person/remote) at weeks 3, 6, 9, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Escitalopram

Trial Overview The study tests escitalopram's safety and effectiveness against placebo for reducing agitation in Alzheimer's patients. Participants will either receive escitalopram or a placebo to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: Escitalopram Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Escitalopram is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lexapro for:

• Major depressive disorder
• Generalized anxiety disorder

Approved in European Union as Cipralex for:

• Major depressive episodes
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder

Approved in Canada as Cipralex for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Who Is Running the Clinical Trial?

JHSPH Center for Clinical Trials

Lead Sponsor

Trials

14

Recruited

11,200+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6889953/

Escitalopram for agitation in Alzheimer's Disease (S-CitAD) Racemic citalopram was effective, with 40% of citalopram-treated participants experiencing clinical improvement vs. 26% on placebo.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40842389/

Efficacy and Safety of Escitalopram and Citalopram for ... ConclusionEscitalopram and citalopram do not significantly reduce agitation in AD but are generally well tolerated. Increased fall risk warrants ...

3. jwatch.org jwatch.org/na58648/2025/04/10/does-escitalopram-prevent-alzheimer-related-agitation

Does Escitalopram Prevent Alzheimer-Related Agitation? At 12 weeks, the proportion of patients whose agitation improved did not differ significantly between the groups (≈30% in each group), nor did ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.085738

Escitalopram for Agitation in Alzheimer's Dementia Citalopram was effective in treating agitation in AD but was associated with cognitive and cardiac risks linked to its R- but not S-enantiomer.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03108846

Escitalopram for Agitation in Alzheimer's Disease This study is designed to examine the efficacy and safety of escitalopram as treatment for agitation in Alzheimer's dementia (AD) patients.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748119303501

When and How to Treat Agitation in Alzheimer's Disease ... In this article, available efficacy and safety data for the use of citalopram and escitalopram in treating agitation in AD dementia is reviewed, using a ...