Lemborexant for Insomnia and Depression

(MDD Trial)

Overseen By Venkat Bhat, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Must not be taking: Sleep aids, Antidepressants

Disqualifiers: Pregnancy, Substance abuse, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Lemborexant, a medication, can alleviate sleep problems in individuals receiving treatment for depression. The researchers seek to discover whether this medication can enhance sleep quality and reduce insomnia symptoms. Participants will take either Lemborexant or a placebo (a non-active look-alike) for six weeks to assess any differences. Suitable candidates have depression, are already undergoing treatment, and continue to experience sleep difficulties. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you keep any current psychiatric medications unchanged for 4 weeks before screening and throughout the study. Additionally, you must not have taken any medications affecting sleep-wake function for at least 4 weeks before starting the study.

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

Research has shown that lemborexant is generally safe for people with insomnia. Some studies found common side effects such as sleepiness, fatigue, dizziness, or nausea. Importantly, lemborexant has not been associated with worsened sleep after discontinuation or withdrawal symptoms.

For individuals with depression or anxiety, studies found that lemborexant improved sleep without introducing new safety concerns. Although some reported nightmares or unusual dreams, these occurrences were uncommon.

Overall, lemborexant appears to be a safe option for managing insomnia, even for those also experiencing depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lemborexant is unique because it targets insomnia and depression by acting on the orexin receptors in the brain. Unlike traditional treatments that often focus on serotonin or dopamine pathways, lemborexant works by blocking orexin, a chemical involved in wakefulness, potentially offering a new approach to both sleep disorders and mood improvement. Researchers are excited about its potential to provide relief with fewer side effects and its promise in managing two conditions simultaneously with a single treatment.

What evidence suggests that Lemborexant might be an effective treatment for insomnia in depression?

Research has shown that Lemborexant, which participants in this trial may receive, helps people with insomnia sleep better. Studies have found that it reduces the time spent awake after falling asleep and improves overall sleep quality. It works well for individuals with insomnia who also experience depression or anxiety. Lemborexant is considered more effective than other insomnia treatments and is generally safe, typically not causing unexpected side effects. Overall, Lemborexant presents a promising option for improving sleep in people with insomnia. ^{1 2 4 6 7}

Who Is on the Research Team?

Venkat Bhat, MD, MSc

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

Adults with major depressive disorder (MDD) who are currently being treated but still experience insomnia can join this trial. They must be willing to take a daily pill, maintain a sleep diary, wear a monitoring device, and attend study visits.

Inclusion Criteria

Meet specific sleep criteria at screening visits 1 and 2

Own a smartphone and have reliable internet access

Provide written informed consent

Exclusion Criteria

Previously participated in any clinical trial of lemborexant

Have known sensitivity to lemborexant or its excipients

I am not using any birth control methods approved by this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take Lemborexant or placebo daily for 6 weeks, with clinical assessments and in-person visits

6 weeks

Multiple in-person visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lemborexant

Trial Overview

The trial is testing Lemborexant against a placebo to see if it improves sleep in people with depression-related insomnia. Participants will start with a lower dose for 2 weeks and then increase the dose for another 4 weeks while their experiences are monitored.

How Is the Trial Designed?

Group I: Lemborexant Experimental Treatment 1 Intervention

Participants will take a 5 mg pill of lemborexant daily for two weeks, followed by a dosage increase to 10 mg daily for the next four weeks (6 weeks total).

Group II: Placebo Placebo Group 1 Intervention

Participants will take a 5 mg of placebo pill daily for 2 weeks then 10 mg daily for 4 weeks (total of 6 weeks).

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Published Research Related to This Trial

In a study involving 291 adults with insomnia, lemborexant doses of 2.5 to 10 mg significantly improved sleep efficiency and reduced sleep onset latency compared to placebo, while minimizing next-morning sleepiness.

The 15 mg dose of lemborexant was particularly effective, leading to early success in the trial, and was associated with mostly mild to moderate side effects like somnolence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. Murphy, P., Moline, M., Mayleben, D., et al.[2018]

In a 12-month phase 3 study involving 949 subjects with moderate to severe insomnia, lemborexant significantly reduced insomnia severity compared to placebo, with improvements maintained over time.

Lemborexant treatment resulted in higher rates of clinically meaningful responses and remissions, with 44%-57% of subjects achieving a significant reduction in insomnia severity after 1 to 6 months, compared to 30%-41% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder. Roth, T., Rosenberg, R., Morin, CM., et al.[2022]

Lemborexant, a dual orexin receptor antagonist, demonstrated significant and sustained improvements in sleep onset and maintenance over twelve months in a study involving 949 participants, with benefits maintained from the initial six months of treatment.

The treatment was generally safe, with most adverse events being mild to moderate, and there was no evidence of rebound insomnia or withdrawal symptoms after discontinuation, indicating its potential for long-term use in managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Yardley, J., Kärppä, M., Inoue, Y., et al.[2021]

Lemborexant has been shown to significantly reduce the time it takes to fall asleep compared to placebo and is also effective when compared to the active control zolpidem ER, based on two phase 3 trials.

The medication is generally well-tolerated, with fewer severe side effects like cognitive impairment and complex sleep-related behaviors compared to traditional insomnia treatments, making it a suitable option, especially for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. Waters, K.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39632341/

Efficacy and safety of lemborexant in subjects with ...

Conclusion: LEM treatment benefited subjects with insomnia treated with medications for depression/anxiety symptoms, with no new safety signals. A greater ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1389945725004988

Efficacy and safety of lemborexant in patients with insomnia

Lemborexant significantly reduced WASO (MD: 20.73 min; 95 % CI: 28.58 to −12.88), improved sleep efficiency (MD: 4.84 %; 95 % CI: 2.69 to 7.00), and reduced ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10394202/

Comparative efficacy of lemborexant and other insomnia ...

CONCLUSIONS: Lemborexant was ranked highest of the treatments studied on 3 out of the 4 objectively measured insomnia efficacy outcomes, with a safety profile ...

4.

nature.com

nature.com/articles/s41398-025-03439-8

a systematic review and network meta-analysis

Therefore, any DORAs may be expected to improve overall sleep quality when administered in doses appropriate for each individual with insomnia.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S1389945721000654

Long-term effectiveness and safety of lemborexant in ...

Lemborexant is a recently approved treatment for adults with insomnia. Over 12 months, lemborexant was effective for all sleep parameters assessed.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11814905/

SAFETY AND EFFICACY OF LEMBOREXANT IN ...

To report the incidence of somnolence, nightmares, abnormal dreams, sleep paralysis, hypnotic hallucinations, suicidal ideation, and suicidal ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06843187

Lemborexant for the Treatment of Residual Insomnia in ...

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021 Apr;80 ...