CBT-I + Lemborexant for Insomnia

Overseen By Manon Lamy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laval University

Must not be taking: Sleep-promoting, Tricyclics, MAOIs, Atypicals

Disqualifiers: Psychotic, Bipolar, Substance use, others

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary aims of this study is to contrast the effectiveness of CBT-I and pharmacotherapy (lemborexant) compared to placebo on sleep and mental health outcomes in people with insomnia disorder and anxiety/depressive symptoms. In addition, the study will evaluate whether insomnia phenotypes (i.e., +/- 6hrs of sleep) at baseline moderate the effectiveness of the intervention on both sleep and mental health outcomes.

Will I have to stop taking my current medications?

The trial requires that you stop taking sleep-promoting medications or cannabis-derived products for sleep more than two nights per week, as well as tricyclic antidepressants, monoamine oxidase inhibitors, or atypical antidepressants. If you are using any of these, you would need to stop before participating.

What data supports the effectiveness of the treatment Cognitive Behavioral Treatment for Insomnia (CBT-I) combined with Lemborexant for insomnia?

Research shows that Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective in improving sleep quality and reducing insomnia symptoms, even when insomnia occurs alongside other medical or psychiatric conditions. While specific data on the combination with Lemborexant is not provided, CBT-I alone has shown large treatment effects and durable results. ^{1 2 3 4 5}

Is the combination of CBT-I and Lemborexant safe for treating insomnia?

Lemborexant has been shown to be safe for treating insomnia in adults, even for up to twelve months, and CBT-I is considered safe without the risk of side effects associated with medications. Both treatments have been evaluated for safety in various conditions, including when insomnia occurs alongside other health issues. ^{6 7 8 9 10}

How does the treatment CBT-I + Lemborexant for insomnia differ from other treatments?

CBT-I (Cognitive Behavioral Therapy for Insomnia) is a well-established treatment for insomnia, focusing on changing sleep habits and misconceptions about sleep. Lemborexant is a medication that helps regulate sleep by blocking certain brain signals that keep you awake. Combining CBT-I with Lemborexant may offer a unique approach by addressing both behavioral and biological aspects of insomnia, potentially enhancing treatment effectiveness compared to using either method alone. ^{2 5 7 11 12}

Research Team

Charles M Morin, PhD

Principal Investigator

Université Laval Centre d'étude des troubles du sommeil

Eligibility Criteria

This trial is for adults over 18 with chronic insomnia and mild anxiety or depression. Participants must meet DSM-5 criteria for insomnia, have an Insomnia Severity Index score above 10, and be able to use digital devices with internet access. They should also understand French or English.

Inclusion Criteria

I can read and understand either French or English.

I can use a smart device or computer and have home internet.

I have been diagnosed with insomnia and my symptoms are severe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either CBT-I, lemborexant, or placebo over an 8-week period with six consultations

8 weeks

6 visits (in-person)

Post-treatment

Participants are assessed for treatment response and side effects

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 visit (in-person)

Treatment Details

Interventions

• Cognitive Behavioral Treatment for Insomnia (CBT-I)
• Lemborexant

Trial Overview The study compares the effectiveness of Cognitive Behavioral Treatment for Insomnia (CBT-I) and Lemborexant medication against a placebo in improving sleep and mental health in people with different subtypes of chronic insomnia.

Participant Groups

Group I: Lemborexant medication Experimental Treatment 1 Intervention

Participants assigned to this group will be prescribed 5 to 10 mg of lemborexant to be taken at bedtime in 5 mg capsules. Lemborexant (Dayvigo) is a Dual Orexin Receptor Antagonist approved by Health Canada for the treatment of adult with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.

Group II: Cognitive Behavioral Treatment for Insomnia (CBT-I) Experimental Treatment 1 Intervention

Participants in this treatment group will receive CBT-I. CBT-I sessions will occur weekly for the first 4 sessions and biweekly for the last 2 sessions (treatment phase is thus 8 weeks). : Graduate level students in clinical psychology will serve as therapists for this project.

Group III: Placebo Placebo Group 1 Intervention

Participants assigned to this group will be prescribed 5 to 10 mg of placebo to be taken at bedtime in 5 mg capsules identical to lemborexant. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.

Who Is Running the Clinical Trial?

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

The Royal Ottawa Mental Health Centre

Collaborator

Trials

24

Recruited

2,300+

Findings from Research

Cognitive behavioral therapy for insomnia (CBT-I) is recognized as the first-line treatment for both uncomplicated insomnia and insomnia associated with other chronic disorders, demonstrating its broad efficacy.

This review aims to summarize efficacy data across various clinical and demographic factors and to outline future research and implementation strategies for CBT-I, highlighting its importance in treating sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

We know CBT-I works, now what? Muench, A., Vargas, I., Grandner, MA., et al.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly improves sleep quality in adults with insomnia and comorbid medical or psychiatric conditions, based on a review of 23 studies involving 1379 patients.

The treatment leads to substantial reductions in sleep onset latency and wake after sleep onset, with benefits lasting up to 18 months, demonstrating its effectiveness and durability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy in persons with comorbid insomnia: A meta-analysis. Geiger-Brown, JM., Rogers, VE., Liu, W., et al.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly improved sleep quality, sleep onset, and sleep efficiency in 76 patients with primary insomnia over a 6-week group course in a clinical setting.

CBT-I also led to reductions in medication use and improvements in patients' overall health and cognitive functioning, highlighting its effectiveness beyond just sleep improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. Van Houdenhove, L., Buyse, B., Gabriels, L., et al.[2018]

Cognitive behavior therapy for insomnia (CBT-I) shows moderate to large treatment effects (Cohen's d range of 0.35-2.2) for patients with insomnia related to various medical and psychiatric conditions, indicating its efficacy beyond primary insomnia.

Improving sleep through CBT-I may also lead to better outcomes in managing comorbid medical and psychological conditions, highlighting the need for further research on adapting CBT-I for specific disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders. Smith, MT., Huang, MI., Manber, R.[2022]

Cognitive Behavioral Therapy for insomnia (CBT-i) is an effective first-line treatment for chronic insomnia, showing significant improvements in sleep onset latency (SOL) by about 19 minutes and wake after sleep onset (WASO) by about 26 minutes based on a review of 20 studies involving 1162 participants.

The benefits of CBT-i, which includes techniques like cognitive therapy and sleep hygiene, appear to be sustained over time, and importantly, no adverse effects were reported, making it a safe alternative to pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis. Trauer, JM., Qian, MY., Doyle, JS., et al.[2022]

Cognitive behavioral therapy for insomnia (CBT-I) is a safe and effective treatment for insomnia, even in patients with various co-occurring mental health and medical conditions.

The article reviews the evidence supporting the use of CBT-I in these populations and discusses important considerations for its application, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Insomnia in Patients with Medical and Psychiatric Comorbidities. Raglan, GB., Swanson, LM., Arnedt, JT.[2019]

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]

In a study of 649 patients with comorbid insomnia and psychiatric disorders, lemborexant was found to be effective, with a response rate of 64.5% and over 60% for most psychiatric conditions.

Lemborexant significantly reduced the dosage of benzodiazepines (BZs) used by patients, indicating its potential to help manage insomnia while decreasing reliance on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. Katsuta, N., Takahashi, K., Kurosawa, Y., et al.[2023]

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]

Cognitive-behavioral therapy for insomnia (CBT-I) showed positive effects on sleep quality and depressive symptoms in a study of 30 psychiatric outpatients, with 38% achieving normal sleep after treatment.

While CBT-I led to significant improvements within the treatment group over 4 and 8 weeks, there were no significant differences when compared to the control group, suggesting that while beneficial, the effects may not be strong enough to outperform standard care alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of abbreviated CBT for insomnia in psychiatric outpatients: sleep and depression outcomes. Wagley, JN., Rybarczyk, B., Nay, WT., et al.[2022]

Cognitive-behavioral therapy for insomnia (CBT-I) is the preferred treatment for chronic insomnia, but it faces challenges such as a lack of trained therapists and a low response rate among patients.

Alternative methods to CBT-I, including bibliotherapy, phone psychotherapy, brief behavioral therapy, and online CBT-I, are gaining interest, and hypnotics can be used alongside CBT-I to enhance its effectiveness or as a standalone treatment when CBT-I is not accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioral therapy and pharmacotherapy for chronic insomnia]. Pchelina, PV., Poluektov, MG.[2019]

References

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

Long-Term Maintenance of Therapeutic Gains Associated With Cognitive-Behavioral Therapy for Insomnia Delivered Alone or Combined With Zolpidem. [2019]

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

We know CBT-I works, now what? [2022]

3. England pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy in persons with comorbid insomnia: A meta-analysis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. [2018]

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

Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders. [2022]

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

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis. [2022]

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

Cognitive Behavioral Therapy for Insomnia in Patients with Medical and Psychiatric Comorbidities. [2019]

8. United States 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. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. [2023]

10. Netherlands 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. [2021]

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

Effectiveness of abbreviated CBT for insomnia in psychiatric outpatients: sleep and depression outcomes. [2022]

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

[Cognitive-behavioral therapy and pharmacotherapy for chronic insomnia]. [2019]