Escitalopram for Depression and Alzheimer's Prevention

Recruiting at 1 trial location

Overseen By Chelsea Reichert Plaska, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: NYU Langone Health

Must not be taking: Fluoxetine, Anti-Parkinsonian, Cholinesterase inhibitors, others

Disqualifiers: Brain tumor, Alcoholism, Schizophrenia, others

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: Unknown

Duration: 8 weeks

60 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

You may need to stop taking certain medications to join the trial. If you are on antidepressants like fluoxetine, you will need a washout period (time without taking the medication). Some medications, like continuous aspirin or NSAIDs, must be temporarily stopped before certain procedures. If you are on stable doses of prescribed psychoactive medications, you may be able to continue them.

What data supports the effectiveness of the drug Escitalopram for preventing Alzheimer's in patients with depression?

Research suggests that selective serotonin reuptake inhibitors (SSRIs), like escitalopram, may improve cognitive performance in Alzheimer's disease, although it's unclear if this is due to direct effects on cognition or mood stabilization. ^{1 2 3 4 5}

Is escitalopram safe for humans?

Escitalopram, also known as Lexapro or Cipralex, is generally considered safe for humans, but like many medications, it can have side effects. Some studies have looked at its use in Alzheimer's disease and depression, and while it may be safer than some antipsychotics, there are concerns about potential heart-related side effects, similar to those seen with citalopram. ^{4 5 6 7 8}

How is the drug escitalopram unique for treating depression and preventing Alzheimer's?

Escitalopram is unique because it is being studied not only for treating depression but also for potentially preventing dementia in patients with depression and cognitive issues related to chronic brain ischemia (reduced blood flow to the brain). Unlike other treatments, it is being explored for its dual role in addressing both mood and cognitive symptoms in Alzheimer's disease. ^{1 4 6 7 9}

What is the purpose of this trial?

This trial will test if treating depression with the antidepressant escitalopram can affect biological markers related to Alzheimer's disease. It targets people with major depressive disorder to see if reducing their depression can also lower their risk of developing Alzheimer's. The study compares escitalopram to understand its effects on these markers. Escitalopram is commonly used to treat major depressive disorder.

Research Team

Nunzio Pomara

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals aged 60+ with major depressive disorder and no cognitive impairment, as indicated by specific mental state and dementia rating scales. Participants must be medically stable, fluent in English, willing to undergo various tests including MRI and lumbar puncture, and not have a significant history of neurological disorders or substance abuse.

Inclusion Criteria

Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening

I can read and understand English at a 6th grade level or higher.

Clinical Dementia Rating Scale (CDR) Global of 0

Exclusion Criteria

I am not currently taking any medications that are excluded from the trial.

I have no unstable heart, lung, hormone, or blood conditions.

I do not have mental retardation or serious neurological disorders like Parkinson's.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the SSRI antidepressant escitalopram or placebo to treat depressive symptoms

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Escitalopram Oxalate
• Placebo

Trial Overview The study compares the antidepressant escitalopram oxalate against a placebo to see if treating depression affects Alzheimer's disease biomarkers. It aims to understand whether improving depression can normalize biological factors linked to Alzheimer's risk.

Participant Groups

Group I: Escitalopram (ESC) Active Control 1 Intervention

Group II: Placebo (PBO) Placebo Group 1 Intervention

Escitalopram Oxalate 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?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Sertraline, a selective serotonin reuptake inhibitor, is one of the most studied antidepressants for treating depression in Alzheimer's Disease, but traditional antidepressants often show only modest benefits due to the unique causes of depression in these patients.

Current research is exploring new drug classes, including those targeting glutamate transmission and the NMDA antagonist ketamine, as potential treatments, highlighting the need for more effective and multimodal approaches to manage depression in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder. Lozupone, M., La Montagna, M., D'Urso, F., et al.[2022]

The DIADS-2 study is a well-structured, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of sertraline, a selective serotonin reuptake inhibitor, for treating depression in Alzheimer’s disease, addressing previous research limitations like small sample sizes and short follow-up periods.

This study includes comprehensive measures of patient and caregiver outcomes, structured psychosocial therapy for caregivers, and ongoing diagnostic evaluations, aiming to provide a thorough understanding of depression in Alzheimer’s patients and its treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of Depression in Alzheimer's Disease Study-2. Martin, BK., Frangakis, CE., Rosenberg, PB., et al.[2022]

Preclinical studies suggest that SSRIs may enhance cognitive function in Alzheimer's disease by acting on the hippocampus, potentially stimulating neurogenesis and reducing amyloid plaque formation, but clinical trials have not consistently measured cognitive outcomes separately from mood stabilization.

Current evidence does not support SSRIs as effective cognition enhancers or disease modifiers in Alzheimer's, highlighting the need for better-designed clinical trials that assess multiple outcome variables, including mood, behavior, and neurochemistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer's disease. Chow, TW., Pollock, BG., Milgram, NW.[2021]

In a study involving 72 patients aged 65-78 with chronic brain ischemia and depression, escitalopram was effective in treating depression and reducing the risk of dementia over a 6-month treatment period.

Both low (5 mg) and higher (10 mg) doses of escitalopram were used, showing that the medication can help manage cognitive dysfunction associated with depression in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of different doses of escitalopram in the prevention of dementia in patients with depression and moderate cognitive dysfunction associated with chronic brain ischemia]. Zhitkova, JV.[2022]

In a 6-month study involving 75 nursing home residents with Alzheimer's disease, citalopram was found to be as effective as quetiapine and olanzapine in reducing agitation, while also resulting in fewer adverse health outcomes.

Citalopram was associated with a lower risk of falls, orthostatic hypotension, and hospitalizations compared to both quetiapine and olanzapine, suggesting it may be a safer option for managing agitation in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia. Viscogliosi, G., Chiriac, IM., Ettorre, E.[2018]

The CitAD study, involving 200 individuals with Alzheimer's disease and significant agitation, evaluated the efficacy of citalopram compared to a placebo, aiming to provide a potential treatment option for this common neuropsychiatric symptom.

The study's design, which included structured psychosocial therapy for caregivers and robust outcome measures, highlights important considerations for future trials assessing psychotropic medications for agitation in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram for agitation in Alzheimer's disease: design and methods. Drye, LT., Ismail, Z., Porsteinsson, AP., et al.[2022]

In a six-week study involving 40 hospitalized Alzheimer's patients, both escitalopram and risperidone were effective in reducing psychotic symptoms and agitation, with no significant difference in overall efficacy between the two medications.

Escitalopram had a higher completion rate (75%) compared to risperidone (55%), and importantly, there were no adverse events reported in the escitalopram group, while risperidone was associated with severe side effects, including extrapyramidal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: a randomized double-blind pilot study. Barak, Y., Plopski, I., Tadger, S., et al.[2022]

Citalopram has shown promising efficacy in treating agitation in Alzheimer's disease dementia, potentially benefiting from a class effect seen in selective serotonin reuptake inhibitors, but concerns about its cardiac side effects have limited its use.

The article reviews safety and efficacy data for both citalopram and escitalopram, providing practical recommendations and risk mitigation strategies to enhance their use in clinical practice for managing agitation in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram. Aga, VM.[2022]

The S-CitAD trial is a randomized, multicenter study investigating the efficacy of 15 mg/day escitalopram in treating agitation in Alzheimer's disease patients who do not respond adequately to standard psychosocial interventions, aiming to improve their overall condition.

The primary outcome measure is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC), which will help assess the effectiveness of escitalopram and potentially establish a new model for treating agitation in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial. Ehrhardt, S., Porsteinsson, AP., Munro, CA., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Design of Depression in Alzheimer's Disease Study-2. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer's disease. [2021]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Comparison of different doses of escitalopram in the prevention of dementia in patients with depression and moderate cognitive dysfunction associated with chronic brain ischemia]. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Citalopram for agitation in Alzheimer's disease: design and methods. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: a randomized double-blind pilot study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial. [2022]