CBT + Trazodone for Insomnia

Recruiting at 4 trial locations

Overseen By Carrie Criley

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Must be taking: Antihypertensives

Must not be taking: Corticosteroids, Opiates, others

Disqualifiers: Psychotic, Bipolar, Narcolepsy, others

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two common treatments for insomnia work for people with different sleep patterns. Participants with chronic insomnia will first try Cognitive Behavioral Therapy for Insomnia (CBT-I), a type of talk therapy. If CBT-I proves ineffective, they will receive either trazodone, a non-addictive sleep medication, or a placebo. The trial aims to determine if individuals with short or normal sleep durations respond differently to these treatments. Those with chronic insomnia and a BMI of 18.5 or higher might be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to foundational insomnia research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use medications for sleep more than twice a week, systemic corticosteroids, opiates, or any medications that don't mix well with trazodone. You must also continue your anti-hypertensive medication if you're on it.

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

Research shows that both treatments in this study are safe. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a safe and effective method, with studies indicating long-lasting benefits and very few risks. Since it doesn't involve medication, there are no drug-related side effects.

Trazodone, used in a low dose for insomnia, is a commonly prescribed medication that is not addictive. Research has found that it can greatly improve sleep time without causing major side effects. However, like any medication, some people might experience mild side effects such as dizziness or a dry mouth.

Overall, both treatments are generally well-tolerated, with trazodone having a few possible mild side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Cognitive Behavioral Treatment for Insomnia (CBT-I) with trazodone because it offers a unique two-step approach to treating insomnia. While most treatments focus solely on either behavioral therapy or medication, this method starts with CBT-I, a well-established therapy that addresses the root causes of insomnia. If patients don't respond fully, trazodone, an antidepressant with sedative effects, is added to enhance sleep quality. This combination could offer a more comprehensive solution by tackling both psychological and physiological aspects of insomnia, potentially leading to better outcomes than current options like sleep medications or CBT-I alone.

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

Research shows that trazodone can help people with insomnia sleep longer, particularly those who typically sleep for a short duration. Trazodone also lowers blood pressure and reduces evening cortisol levels, a hormone related to stress. In this trial, some participants will receive Cognitive Behavioral Therapy for Insomnia (CBT-I) with trazodone. Conversely, CBT-I works well for individuals with insomnia who already sleep a normal amount, showing about a 30% higher success rate for this group. Other participants in this trial will receive CBT-I with a placebo. Both treatments effectively address long-term insomnia and have few side effects. These findings suggest that both trazodone and CBT-I can be helpful, but their success may depend on the type of insomnia present. ^{1 3 6 7 8}

Who Is on the Research Team?

Alexandros Vgontzas, MD

Principal Investigator

Professor, Psychiatry

Are You a Good Fit for This Trial?

This trial is for adults with chronic insomnia, particularly those who sleep less than normal (ISS) or have a normal sleep duration (INS), and also have high blood pressure. Participants should not be currently using other treatments for insomnia.

Inclusion Criteria

Body Mass Index (BMI) 18.5-<40 kg/m2

I can read and communicate effectively in English or French (in Canada).

I have been diagnosed with chronic insomnia.

Exclusion Criteria

I am not willing to share my contact details for surveys.

Unstable medical conditions that would make participation unsafe or unfeasible

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cognitive Behavioral Therapy for Insomnia (CBT-I) for 8 weeks. Non-remitting subjects then receive either trazodone or placebo for an additional 8 weeks.

16 weeks

Follow-up

Participants are monitored for remission of insomnia symptoms and other secondary outcomes such as cortisol levels and blood pressure.

35 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Treatment for Insomnia (CBT-I)
• Placebo
• Trazodone

Trial Overview The study tests Cognitive Behavioral Therapy for Insomnia (CBT-I), which is a non-drug treatment focusing on changing sleep habits, versus Trazodone, a low-dose medication that helps with sleep without forming habits. The effectiveness of these treatments will be compared.

How Is the Trial Designed?

Group I: Subjects treated with Cognitive Behavior Treatment for Insomnia (CBT-I) with Trazodone Active Control 2 Interventions

Subjects with insomnia treated with Cognitive Behavior Treatment for Insomnia (CBT-I) for 8 weeks, then non-remitting subjects received trazodone for 8 weeks.

Group II: Subjects treated with Cognitive Behavior Treatment for Insomnia (CBT-I) with placebo Placebo Group 2 Interventions

Subjects with insomnia treated with Cognitive Behavior Treatment for Insomnia (CBT-I) for 8 weeks, then non-remitting subjects received placebo for 8 weeks.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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) 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) 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) significantly improves insomnia symptoms, with 36% of patients achieving remission compared to only 16.9% in control groups, indicating its efficacy for those with comorbid conditions.

CBT-I shows medium to large effect sizes for various sleep parameters, such as sleep efficiency and sleep onset latency, and has a small positive effect on comorbid symptoms, particularly benefiting patients with psychiatric conditions more than those with medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis. Wu, JQ., Appleman, ER., Salazar, RD., et al.[2022]

Cognitive Behaviour Therapy (CBT) alone and in combination with trazodone is effective for treating chronic primary insomnia, as shown in a study of 20 outpatients over 8 weeks, with significant improvements in sleep latency, efficiency, and total sleep time.

The combination of CBT and trazodone notably increased slow wave sleep duration compared to CBT alone, suggesting that trazodone enhances sleep quality independently of its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone improves the results of cognitive behaviour therapy of primary insomnia in non-depressed patients. Zavesicka, L., Brunovsky, M., Horacek, J., et al.[2018]

Cognitive-behavioral therapy for insomnia (CBT-I) is recognized as the best treatment for chronic insomnia, yet it is significantly underutilized despite the high number of people affected by insomnia disorder.

The article highlights the need for further research on how to effectively deliver CBT-I, identify suitable candidates for the therapy, and measure the quality of care provided, which are essential for improving its real-world application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivering Cognitive Behavioral Therapy for Insomnia in the Real World: Considerations and Controversies. Buenaver, LF., Townsend, D., Ong, JC.[2019]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7848933/

Effects of trazodone versus cognitive behavioral therapy in ... The current preliminary, open-label, randomized trial suggests that trazodone, but not CBT-I, significantly improves objective sleep duration.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04468776

NCT04468776 | CBT-I or Zolpidem/Trazodone for Insomnia This study is a randomized (1:1:1) comparative effectiveness trial of medication (zolpidem or trazodone), cognitive-behavioral therapy for insomnia (CBT-I), ...

3. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A235/8135772

0540 Comparative Effectiveness of Medication, Digital CBT-I ... Side effects were minimal in all groups. All three treatments showed robust effectiveness for chronic insomnia in primary care practices.

4. pure.psu.edu pure.psu.edu/en/projects/12-cognitive-behavioral-therapy-and-trazodone-effects-on-sleep-an

1/2 Cognitive Behavioral Therapy and Trazodone Effects ... Trazodone, but not CBT-I, increases objective total sleep time (TST), and lowers BP and evening cortisol in ISS.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1087079222001496

Cognitive-behavioral therapy for insomnia with objective ... The main outcome was that CBT-I had a better efficacy for the INS phenotype compared with the ISS phenotype, with about 30% higher response and about 20% ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06281756

Cognitive Behavioral Therapy and Trazodone Effects on ... This study will examine whether patients with ISS and INS demonstrate a differential response to two common insomnia treatments. One is behavioral, Cognitive ...

7. nature.com nature.com/articles/s41746-025-01847-0

A randomized controlled trial of a digital cognitive ... Meta-analyses support CBT-I as efficacious and safe, with long-lasting effects in older adults. As a behavioral rather than pharmacological ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10002474/

Cognitive Behavioral Therapy for Insomnia (CBT-I): A Primer CBT-I is a multi-component treatment for insomnia that targets difficulties with initiating and/or maintaining sleep and is delivered over the course of six to ...