Donepezil for Anorexia

Overseen By Joanna Steinglass, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Antipsychotics

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the feasibility and tolerability of donepezil in a small group of patients with anorexia nervosa (AN). Study participants will be receiving care at the New York State Psychiatric Institute Eating Disorders Unit. Study medication will be increased from 1 mg per day to a maximum of 5 mg per day for up to 8 weeks. Participants will be closely monitored for side effects by a research psychiatrist every week, in addition to the regular clinical monitoring they receive during inpatient treatment. The study will also include assessments of habit strength to measure any changes in maladaptive eating habits over the course of the treatment.

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

The trial does not specify if you need to stop taking your current medications, but it does allow antidepressants if they are at a stable dose. Antipsychotic medications are not allowed.

Is donepezil generally safe for humans?

Donepezil, commonly used for Alzheimer's disease, is generally safe at lower doses like 10 mg, but higher doses such as 23 mg can cause more gastrointestinal side effects (like stomach issues). It has been studied for other conditions, but safety data primarily comes from Alzheimer's research. ^{1 2 3 4 5}

How does the drug donepezil differ from other treatments for anorexia?

Donepezil is unique for treating anorexia because it works by increasing acetylcholine, a brain chemical, which is similar to its use in Alzheimer's disease. This approach is novel for anorexia, as it targets neurological aspects of the condition, unlike other treatments that may focus more on psychological or nutritional interventions. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for individuals with anorexia nervosa receiving care at the New York State Psychiatric Institute Eating Disorders Unit. Participants will be given donepezil, starting at 1 mg per day and potentially increasing to 5 mg daily over 8 weeks.

Inclusion Criteria

Provision of signed and dated informed consent form

I am willing and able to follow all study requirements.

I am between 18 and 60 years old.

Exclusion Criteria

I have a history of irregular heartbeats.

Current diagnosis of schizophrenia, schizophreniform disorder, bipolar (type I), or substance use disorder (SCID)

Bradycardia (below 60 bpm) (vital signs measurement by the clinical team)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive donepezil with flexible titration from 1 mg to 5 mg over 8 weeks

8 weeks

Weekly visits with a research psychiatrist

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Donepezil

Trial Overview The study aims to test the feasibility and tolerability of donepezil in patients with anorexia nervosa. The medication dosage may increase gradually, and changes in maladaptive eating habits will be monitored throughout the treatment.

Participant Groups

Group I: Open Label Experimental Treatment 1 Intervention

Donepezil

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

Approved in European Union as Aricept for:

• Alzheimer's disease

Approved in United States as Aricept for:

• Alzheimer's disease
• Mild to moderate dementia of the Alzheimer's type

Approved in Canada as Aricept for:

• Alzheimer's disease

Approved in Japan as Aricept for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Findings from Research

In a 12-week study involving 468 patients with mild to moderately severe Alzheimer disease, donepezil hydrochloride significantly improved cognitive function and clinical outcomes compared to placebo, with notable improvements in ADAS-cog and CIBIC plus scores.

Donepezil was well-tolerated, with a similar incidence of side effects compared to placebo, and did not show the hepatotoxic effects seen with other cholinesterase inhibitors, making it a safe option for treating Alzheimer's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Rogers, SL., Doody, RS., Mohs, RC., et al.[2022]

In a 24-week study involving 30 adults with Down syndrome and mild to moderate Alzheimer's disease, donepezil was found to be generally safe and well-tolerated, with no life-threatening side effects reported.

While the results showed some potential efficacy, with 50% of donepezil patients improving in dementia scores compared to 31% on placebo, the small sample size limited the statistical significance of these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. Prasher, VP., Huxley, A., Haque, MS.[2019]

In a study of 160 patients with moderate to severe Alzheimer's disease, those with lower body weight were more likely to experience adverse events (AEs) when treated with high-dose donepezil (23 mg), indicating a safety concern for this population.

The analysis suggests that using a stepwise dose titration approach, especially for patients with low body weight, may help reduce the risk of AEs associated with donepezil treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer's Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial. Hong, YJ., Han, HJ., Youn, YC., et al.[2021]

A retrospective analysis of 41 elderly Alzheimer's patients from various ethnic backgrounds showed that Donepezil (Aricept) is clinically effective for treating mild to moderate Alzheimer's disease.

The study suggests that Donepezil's efficacy is consistent across different ethnicities, including a significant number of Asian and Hawaiian patients, even in older age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of donepezil in elderly patients with Alzheimer's disease--a Hawaii based study. Alagiakrishnan, K., Wong, W., Blanchette, PL.[2022]

Donepezil is rapidly absorbed after oral administration, with most of the drug remaining unchanged in the brain, indicating that it effectively crosses the blood-brain barrier while its metabolites do not.

The drug is primarily excreted through feces, with extensive metabolism occurring in the body, but no significant accumulation of its metabolites in the brain or other tissues, suggesting a low risk of toxicity from these byproducts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat. Matsui, K., Mishima, M., Nagai, Y., et al.[2018]

References

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

Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. [2022]

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

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. [2019]

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

Donepezil 23 mg: An empty suit. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Donepezil (aricept) as a treatment for anorexia nervosa: a very feasible therapeutic possibility. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer's Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial. [2021]

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

Use of donepezil in elderly patients with Alzheimer's disease--a Hawaii based study. [2022]

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

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat. [2018]