e-CBTi vs Trazodone for Insomnia

Overseen By Nazanin Alavi, MD FRCPC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dr. Nazanin Alavi

Must be taking: Sleep-promoting medications

Disqualifiers: Untreated sleep disorder, Substance use, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 7 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Insomnia is defined as the inability to fall asleep or stay asleep at night and it is one of the most prevalent sleep disorders that can have deleterious impacts on health and this population's quality of life. Currently, both pharmaceutical interventions (trazodone) and cognitive behavioral therapy (CBTi) are widely used to treat patients with insomnia. Although CBTi has been efficacious in many patients, multitude of barriers for receiving treatment such as its limited availability of therapists, high costs and long wait times challenge its ability in sufficiently meeting the population's health needs and demands. To improve the delivery of CBT, electronically delivered CBTi (e-CBTi) has been developed as an accessible and effective alternative intervention for improving sleep outcomes in patients with insomnia. While evidence suggest that e-CBTi is effective when compared to placebos/waitlist control, evidence comparing guided e-CBTi to pharmaceutical interventions is still insufficient and needs further exploration.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves comparing e-CBTi to trazodone, you might be required to continue using sleep-promoting medication if you are already doing so.

What data supports the effectiveness of the treatment e-CBTi for insomnia?

Research shows that digital cognitive behavioral therapy for insomnia (dCBT-I) is effective in treating insomnia, improving sleep quality, and enhancing overall well-being and quality of life. Studies also suggest that adding personalized telephone sessions to dCBT-I can provide additional benefits for those with chronic insomnia. ^{1 2 3 4 5}

Is digital CBT-I safe for treating insomnia?

Digital CBT-I is considered a safe treatment for insomnia, as it avoids the adverse effects often associated with medication and has been shown to improve sleep quality and well-being. ^{4 6 7 8 9}

How does the treatment e-CBTi differ from other treatments for insomnia?

e-CBTi (digital cognitive behavioral therapy for insomnia) is unique because it is delivered online, making it more accessible and scalable compared to traditional face-to-face therapy. Unlike trazodone, a medication that alters brain activity during sleep, e-CBTi focuses on changing sleep-related behaviors and thoughts, which can also help with related issues like depression and anxiety. ^{1 2 8 10 11}

Research Team

Nazanin Alavi, MD FRCPC

Principal Investigator

Queen's University

Eligibility Criteria

This trial is for adults with non-organic insomnia who struggle to fall or stay asleep for at least 30 minutes. Participants must have internet access, use sleep meds thrice a week for 3 months, and understand English. It's not for pregnant individuals, those with untreated sleep disorders or substance abuse issues, current CBT patients, or people with significant untreated health problems.

Inclusion Criteria

Ability to speak and read English

Consistent and reliable access to the internet

I am 18 years old or older.

Exclusion Criteria

Pregnancy

Alcohol or substance use disorder

I have an untreated sleep disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomly assigned to either e-CBTi or trazodone treatment for 7 weeks

7 weeks

Weekly online sessions for e-CBTi group; Monthly in-person visits for trazodone group

Follow-up

Participants are monitored for changes in sleep quality and insomnia severity after treatment

4 weeks

2 visits (in-person)

Open-label extension (optional)

Participants in the trazodone group may opt into the e-CBTi program after the 7-week study period

Optional

Treatment Details

Interventions

• e-CBTi
• Trazodone

Trial Overview The study compares e-CBTi—an online cognitive behavioral therapy—and Trazodone—a medication—to see which is more effective in treating insomnia. The goal is to determine if e-CBTi can be an accessible alternative to traditional treatments.

Participant Groups

Group I: e-CBTi Experimental Treatment 1 Intervention

The e-CBTi modules will involve guiding participants to develop constructive and balanced strategies that would help to handle sleep problems. The e-CBTi program is based on the idea that insomnia is caused by thoughts and behaviours that can be changed. The modules aim to adjust negative thinking so patients can think about and adapt to the events that are happening to them, allowing them to adjust their behaviour and thoughts to be more realistic. Continuing, the modules are designed to help patients with insomnia deal with inaccurate thoughts about sleep and negative sleep behaviours, change their lifestyle practices that negatively affect their sleep, and improve relaxation skills to improve healthy sleep patterns. More specifically, the focus of the program is on addressing and exploring the concept of sleep, sleep habits, sleep hygiene, bedtime worries, negative thoughts, and thought examination.

Group II: Pharmacotherapy Active Control 1 Intervention

Trazodone is the treatment of choice for insomnia and participants allocated to the pharmaceutical intervention group will be prescribed trazodone as a regular treatment for the duration of the study. Participants on trazodone will also visit the psychiatrist every month to ensure their wellbeing is protected, the quality of the data is maintained, the conduct of the trial is in compliance with the approved protocol, and other regulatory requirements. Trazodone is the routine practice for insomnia and is covered through most patients' healthcare. However, if the patient does not have coverage for trazodone, they will be provided financial compensation to offset the cost.

e-CBTi is already approved in United States, European Union for the following indications:

Approved in United States as Somryst for:

• Insomnia

Approved in European Union as Digital CBT-I for:

• Insomnia

Who Is Running the Clinical Trial?

Dr. Nazanin Alavi

Lead Sponsor

Trials

14

Recruited

1,100+

Dr. Nazanin Alavi

Lead Sponsor

Trials

14

Recruited

1,100+

Queen's University

Lead Sponsor

Trials

382

Recruited

122,000+

Online PsychoTherapy Clinic

Collaborator

Trials

9

Recruited

710+

Findings from Research

Digital cognitive behavioral therapy (dCBT) significantly improves functional health, psychological well-being, and sleep-related quality of life in individuals with insomnia, based on a study of 1711 participants over 24 weeks.

The reduction in insomnia symptoms was a key factor mediating these improvements, highlighting that dCBT effectively addresses both daytime and nighttime issues related to poor sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. Espie, CA., Emsley, R., Kyle, SD., et al.[2023]

Integrating personalized telephone sessions with digital cognitive behavior therapy for insomnia (TD-CBTI) significantly improved treatment outcomes, leading to a 167% increase in the odds of achieving remission from insomnia compared to standard D-CBTI alone.

Patients receiving TD-CBTI also had a 352% higher likelihood of successfully reducing their sleep medication use, highlighting the added clinical benefits of personalized support in managing chronic insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The beneficial effects of integrating a personalized telephone-delivered component into digital cognitive behavioral therapy for insomnia in a large, hospital-based population. Ren, R., Zhang, Y., Shi, Y., et al.[2023]

In a study involving 1720 adults with insomnia, digital cognitive behavioral therapy for insomnia (dCBT-I) significantly reduced intraindividual variability in sleep metrics, particularly in sleep onset latency, which is crucial for improving sleep quality.

The reduction in variability in sleep metrics was found to mediate significant improvements in both insomnia severity and psychological distress, highlighting the effectiveness of dCBT-I as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of sleep-wake intraindividual variability in digital cognitive behavioral therapy for insomnia: a mediation analysis of a large-scale RCT. Vestergaard, CL., Vedaa, Ø., Simpson, MR., et al.[2021]

Digital cognitive behavioral therapy (dCBT) significantly improves functional health, psychological well-being, and sleep-related quality of life in adults with chronic insomnia, with these benefits sustained up to 48 weeks after treatment.

dCBT also reduces the use of both prescription and non-prescription sleep medications compared to sleep hygiene education, indicating its effectiveness in managing insomnia without relying heavily on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial. Luik, AI., Marsden, A., Emsley, R., et al.[2021]

Digital cognitive behavior therapy for insomnia (dCBT-I) significantly improves sleep quality in patients with insomnia, particularly in those with anxiety disorders, as shown in a study of 6,002 patients over a 12-week period.

Patients receiving dCBT-I monotherapy and those with combined therapy showed notable improvements in sleep quality, with the most significant changes observed in the anxiety group, indicating that dCBT-I is a practical and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital cognitive behavior therapy for insomnia improving sleep quality: a real-world study. Liang, S., Mao, H., Yang, J., et al.[2022]

Digital cognitive behavioural therapy for insomnia (dCBT-I) significantly reduces insomnia severity, with a mean difference of -5.00 on the Insomnia Severity Index (ISI) immediately after treatment, based on a meta-analysis of 33 studies involving nearly 9,400 participants.

The benefits of dCBT-I are sustained over time, showing continued improvement at both short-term (4 weeks to 6 months) and 1-year follow-ups, making it a promising alternative to traditional face-to-face therapy, which, while slightly more effective, falls within a non-inferiority margin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of digital cognitive behavioural therapy for insomnia: a meta-analysis of randomised controlled trials. Soh, HL., Ho, RC., Ho, CS., et al.[2021]

Cognitive behavioral therapy for insomnia (CBTI) is the recommended first-line treatment for insomnia, but its high cost and limited availability of trained providers hinder access, especially for vulnerable groups like military personnel and the elderly.

Digital CBTI (dCBTI) is emerging as a promising and scalable alternative that could improve access to effective insomnia treatment, particularly for those who face barriers to traditional CBTI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insomnia overview: epidemiology, pathophysiology, diagnosis and monitoring, and nonpharmacologic therapy. Dopheide, JA.[2021]

Digital cognitive behavioral therapy for insomnia (dCBT-I) significantly improves sleep outcomes with a large effect size (SMD = -0.76) and also alleviates depressive (SMD = -0.42) and anxiety symptoms (SMD = -0.29) in adults with insomnia, based on a meta-analysis of 22 randomized controlled trials involving 2504 articles.

Higher treatment adherence to dCBT-I correlates with better outcomes in alleviating depression, anxiety, and insomnia symptoms, and fully automated dCBT-I treatments show significant effects without the need for therapist support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital cognitive behavioral therapy for insomnia on depression and anxiety: a systematic review and meta-analysis. Lee, S., Oh, JW., Park, KM., et al.[2023]

Cognitive Behavioral Therapy for insomnia (CBTi) is an effective alternative to medication for treating insomnia, which affects up to 30% of adults, and has been shown to improve various sleep-related outcomes such as sleep onset latency and sleep quality.

CBTi includes techniques like sleep hygiene and cognitive therapy, making it a safe and beneficial option for both adults and adolescents, although access to this therapy can be limited by certain barriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy in the Treatment of Insomnia. Haynes, J., Talbert, M., Fox, S., et al.[2018]

In a study of 19 participants with chronic insomnia, trazodone significantly decreased fast-frequency EEG activity (sigma and beta power) during NREM sleep compared to cognitive-behavioral treatment for insomnia (CBT-I), indicating a stronger effect on reducing hyperarousal.

Trazodone also increased delta power during NREM sleep, suggesting it may enhance deeper sleep, while CBT-I did not show significant changes in EEG activity, highlighting the different mechanisms of action between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of trazodone versus cognitive-behavioural treatment on high- and slow-frequency activity during non-rapid eye movement sleep in chronic insomnia: A pilot, randomized clinical trial. Li, Y., Vgontzas, AN., Fernandez-Mendoza, J., et al.[2022]

Internet-based cognitive behavioral therapy for insomnia (iCBT-I) is perceived as effective and well-structured by psychiatric patients, leading to improvements in sleep quality and daily routines, despite challenges in maintaining motivation during difficult life events.

Participants reported that having contact with a therapist was crucial for motivation, suggesting that additional social support and adjustments could enhance the effectiveness of iCBT-I in secondary psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secondary psychiatric care patients' experiences of internet CBT for insomnia - a qualitative study. Nicolaisen Sidén, F., Spak, F.[2022]

References

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

Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The beneficial effects of integrating a personalized telephone-delivered component into digital cognitive behavioral therapy for insomnia in a large, hospital-based population. [2023]

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

The effect of sleep-wake intraindividual variability in digital cognitive behavioral therapy for insomnia: a mediation analysis of a large-scale RCT. [2021]

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

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Digital cognitive behavior therapy for insomnia improving sleep quality: a real-world study. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of digital cognitive behavioural therapy for insomnia: a meta-analysis of randomised controlled trials. [2021]

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

Insomnia overview: epidemiology, pathophysiology, diagnosis and monitoring, and nonpharmacologic therapy. [2021]

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

Digital cognitive behavioral therapy for insomnia on depression and anxiety: a systematic review and meta-analysis. [2023]

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

Cognitive Behavioral Therapy in the Treatment of Insomnia. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Effect of trazodone versus cognitive-behavioural treatment on high- and slow-frequency activity during non-rapid eye movement sleep in chronic insomnia: A pilot, randomized clinical trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Secondary psychiatric care patients' experiences of internet CBT for insomnia - a qualitative study. [2022]