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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments for insomnia: e-CBTi and trazodone. Insomnia makes falling or staying asleep difficult and can significantly impact daily life. The trial aims to evaluate the effectiveness of e-CBTi, an online therapy program that helps change negative sleep thoughts and habits, against trazodone, a common sleep medication. Individuals with non-organic insomnia who struggle to sleep for at least 30 minutes and have used sleep medications three or more nights a week over the last three months may be suitable for this study. Participants must have reliable internet access and be able to speak and read English. As an unphased trial, this study offers a unique opportunity to explore innovative treatments for insomnia.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that e-CBTi (online Cognitive Behavioral Therapy for Insomnia) can be as effective as in-person therapy for treating insomnia. Studies have found it significantly improves sleep quality and increases treatment accessibility for patients. e-CBTi is generally well-tolerated, with few reported side effects. It works by changing negative thoughts and behaviors that interfere with sleep, making it a low-risk option for many.

In contrast, trazodone is a medication often used to help with insomnia. Research has found that trazodone effectively reduces nighttime awakenings and improves sleep quality for most users. It is considered low-risk for most people, but some safety concerns exist. There is potential for misuse and dependence, and it can have side effects. Monitoring these is important when taking trazodone.

Both treatments are effective and generally safe but work differently. e-CBTi focuses on mental strategies, while trazodone affects brain chemicals. Consulting a healthcare provider is essential to determine the best option for individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about e-CBTi for insomnia because it addresses the condition through a psychological approach rather than medication. Most treatments, like Trazodone, involve pharmaceuticals that may come with side effects and dependency risks. e-CBTi helps patients by changing negative thoughts and behaviors related to sleep, promoting healthier sleep habits without medication. This method empowers individuals to manage their insomnia through cognitive and behavioral adjustments, offering a sustainable and non-pharmacological alternative.

What evidence suggests that this trial's treatments could be effective for insomnia?

This trial will compare e-CBTi, an online therapy for insomnia, with trazodone, a common sleep medication. Research has shown that e-CBTi significantly improves sleep problems, helping individuals sleep better, longer, and more efficiently, with lasting benefits. In contrast, research on trazodone has produced mixed results. Trazodone can increase sleep time and quality, but some studies found it doesn't improve sleep efficiency much compared to a placebo. Both treatments offer benefits, but current evidence suggests e-CBTi is more effective for overall sleep improvement. Participants in this trial will receive either the e-CBTi or trazodone treatment to evaluate their effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Nazanin Alavi, MD FRCPC

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

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 have been diagnosed with insomnia not caused by a physical condition.

Exclusion Criteria

Pregnancy

Alcohol or substance use disorder

I have an untreated sleep disorder.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 (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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5842888/

Trazodone for Insomnia: A Systematic Review - PMC This review article has found that trazodone can be an effective option when treating insomnia with little to no risk in most cases.

2. aafp.org aafp.org/pubs/afp/issues/2023/0200/fpin-ci-trazodone-insomnia.html

Is Trazodone Effective and Safe for Treating Insomnia? When trazodone was compared with placebo, there was no significant improvement in sleep efficiency (standardized mean difference [SMD] = 0.09; 95% CI, −0.19 to ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39123094/

Effects of Trazodone on Sleep: A Systematic Review and ... Trazodone extends total sleep time but does not affect perceived sleep duration. It may improve sleep quality and continuity but has minor effects on sleep ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945718300248

Trazodone for the treatment of insomnia: a meta-analysis ... Trazodone was effective in sleep maintenance by decreasing the number of early awakenings and it could significantly improve perceived sleep quality.

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.8740

Effects of trazodone versus cognitive behavioral therapy in the ... The current randomized trial suggests that trazodone, but not CBT-I, significantly improves objective sleep duration and reduces hypothalamic-pituitary-adrenal ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470560/

Trazodone - StatPearls - NCBI Bookshelf - NIH Clinical studies have shown trazodone is comparable in efficacy to other drug classes, such as tricyclic antidepressants (TCAs), selective serotonin reuptake ...

7. jns-journal.com jns-journal.com/article/S0022-510X(23)01708-2/fulltext

Trazodone in the off-label treatment of insomnia: Abuse ... Data from multiple national sources demonstrate that trazodone has abuse/dependence potential and important safety risks.