Trazodone for Early Alzheimer's Disease

(REST Trial)

Overseen By Paul Rosenberg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Sleep medications

Disqualifiers: Under 55, Sleep apnea, Dementia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking sleep medications, including trazodone, before participating.

What data supports the effectiveness of the drug trazodone for early Alzheimer's disease?

Research suggests that trazodone may help improve sleep and reduce irritability in Alzheimer's patients, and it has been associated with a slower rate of cognitive decline compared to those not using it. It is commonly used to treat sleep disorders in dementia, showing effectiveness in improving sleep quality. ^{1 2 3 4 5}

Is trazodone safe for humans, especially those with Alzheimer's disease?

Trazodone has been used in studies with Alzheimer's patients to help with sleep and behavioral issues, showing it can be a good option for elderly patients with dementia. It is generally considered safe, with no increase in behavioral symptoms or caregiver burden over six months, but there is limited information on its risk of falls and fractures. ^{1 2 3 4 6}

How does the drug trazodone differ from other treatments for Alzheimer's disease?

Trazodone is unique because it not only helps improve sleep disturbances in Alzheimer's patients but also potentially slows cognitive decline by enhancing deeper phases of sleep, unlike other sedative medications that may worsen cognitive function over time. ^{1 2 3 4 5}

What is the purpose of this trial?

To investigate the effect of trazodone on sleep, hippocampal-dependent memory and hippocampal excitability. The investigators hypothesize that trazodone will improve total sleep time and proportion of time in Slow Wave Sleep (SWS).

Research Team

Barry Greenberg, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults with mild cognitive impairment, memory problems, and sleep complaints. They must be in good health, able to undergo MRI scans, and have a caregiver who can provide information. Excluded are those under 55, with severe sleep apnea or dementia, allergic to trazodone, using sleep meds or substances, having major psychiatric episodes or unstable medical conditions.

Inclusion Criteria

Are you older than 55?

Are you willing to wear a sleep monitor for four nights during the study? And are you willing to wear an actiwatch (like a fitbit) during the study?

Are you willing and able to undergo MRI brain imaging?

Exclusion Criteria

Are you currently taking Trazadone?

Are you currently taking any sleep medications that you're not willing or able to stop for two weeks prior to the study?

Do you need to use a CPAP?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trazodone or placebo for 4 weeks each, with a 4-week washout period in between

12 weeks

Multiple visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Trazodone

Trial Overview The study tests if Trazodone improves sleep and memory in early Alzheimer's by increasing total sleep time and Slow Wave Sleep (SWS). Participants will either receive Trazodone or a placebo without knowing which one they're taking.

Participant Groups

Group I: Trazodone First Active Control 2 Interventions

Trazodone (50 mg at bedtime) and then placebo after a 4-week washout period.

Group II: Placebo First Placebo Group 2 Interventions

Placebo and then Trazodone (50 mg at bedtime) after a 4-week washout period.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a review of two studies involving 104 participants with dementia, trazodone did not show statistically significant benefits over placebo for managing behavioral and psychological symptoms associated with dementia.

Despite its sedative and antidepressant properties, the evidence is insufficient to recommend trazodone for dementia-related behavioral disturbances, highlighting the need for longer and larger trials to better assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for agitation in dementia. Martinon-Torres, G., Fioravanti, M., Grimley, EJ.[2022]

In a randomized controlled trial involving 30 patients with Alzheimer's disease, trazodone significantly improved sleep duration by an average of 42.5 minutes per night compared to placebo, indicating its efficacy in treating sleep disturbances.

Trazodone did not cause significant daytime sleepiness or cognitive impairment, suggesting it is a safe option for managing sleep issues in Alzheimer's patients without negatively affecting their cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. Camargos, EF., Louzada, LL., Quintas, JL., et al.[2022]

In a study of 396 patients with Alzheimer's disease, trazodone was prescribed to 6.1% of patients, primarily for symptoms like irritability and agitation, and it effectively reduced irritability without increasing behavioral symptoms or caregiver burden over 6 months.

Patients treated with trazodone showed no worsening in overall behavioral and psychological symptoms of dementia (BPSD) or caregiver burden, indicating its safety and potential efficacy in managing specific symptoms in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for Alzheimer's disease: a naturalistic follow-up study. López-Pousa, S., Garre-Olmo, J., Vilalta-Franch, J., et al.[2022]

In a study of 178 elderly patients with dementia, 38.2% experienced sleep disorders, with trazodone being the most commonly prescribed treatment, used by 35 patients.

Trazodone demonstrated an effectiveness rate of 65.7% in improving sleep disorders among these patients, indicating it is a viable treatment option for elderly individuals with dementia-related sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study. Camargos, EF., Pandolfi, MB., Freitas, MP., et al.[2019]

In a study of 25 participants with Alzheimer's disease or mild cognitive impairment, those taking trazodone for sleep experienced a significantly slower cognitive decline compared to non-users, with a decline rate 2.4 times greater in non-users over four years.

Trazodone not only improves sleep quality, particularly enhancing deep slow-wave sleep, but also has a unique mechanism of action affecting serotonin and adrenergic receptors, suggesting it may have potential benefits for cognitive health in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Alzheimer's Disease: Trazodone, Sleep, Serotonin, Norepinephrine, and Future Directions. Ashford, JW.[2020]

In a study of 9,463 older adults with dementia, trazodone was found to have similar rates of falls and major osteoporotic fractures compared to atypical antipsychotics, indicating it is not necessarily a safer option for this population.

However, trazodone was associated with a lower rate of all-cause mortality, suggesting it may have some advantages in terms of overall survival compared to atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study. Watt, JA., Gomes, T., Bronskill, SE., et al.[2022]

References

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

Trazodone for agitation in dementia. [2022]

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

Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Trazodone for Alzheimer's disease: a naturalistic follow-up study. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of Alzheimer's Disease: Trazodone, Sleep, Serotonin, Norepinephrine, and Future Directions. [2020]

6. Canada pubmed.ncbi.nlm.nih.gov

Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study. [2022]