Trazodone for Obstructive Sleep Apnea

Overseen By Ludovico Messineo

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, Barbiturates, SNRIs/SSRIs, others

Disqualifiers: Neuromuscular disease, Heart failure, others

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether trazodone, a medication often used for depression, can help people with obstructive sleep apnea (OSA) by reducing the severity of breathing disruptions during sleep. The focus is on individuals with moderate-to-severe OSA who wake up too early during breathing pauses and cannot naturally open their airways. Participants will take either trazodone or a placebo before bed to determine its impact. Those with OSA experiencing at least 15 events of disrupted breathing per hour and no other major health issues may be suitable for this study. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including those that stimulate or depress breathing, SNRIs/SSRIs, and medications that lengthen the QTc interval. If you are on any of these, you may need to stop them to participate.

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

Research has shown that trazodone has been studied as a treatment for sleep problems, including obstructive sleep apnea (OSA). One study found that trazodone reduced the number of breathing interruptions each hour compared to a placebo, suggesting it might help with OSA symptoms without causing major side effects. Another study found that trazodone made it harder to wake up during sleep, but its overall impact on sleep apnea severity remains unclear. These findings suggest that trazodone is generally well-tolerated by people with sleep disorders. Participants should discuss potential risks and benefits with their doctors before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea?

Most treatments for obstructive sleep apnea (OSA), like CPAP machines or oral appliances, focus on physically keeping airways open during sleep. But trazodone works differently, targeting the central nervous system to improve sleep quality and reduce apnea episodes. Researchers are excited about trazodone because it offers a non-mechanical approach, potentially benefiting those who struggle with the discomfort or inconvenience of current devices. Additionally, trazodone is taken as a simple capsule before bedtime, which could make it more convenient and user-friendly.

What evidence suggests that trazodone might be an effective treatment for obstructive sleep apnea?

Research has shown that trazodone, which participants in this trial may receive, might help people with obstructive sleep apnea (OSA). One study found that trazodone lowered the apnea-hypopnea index (AHI), which measures how often breathing stops or becomes shallow during sleep. Specifically, the AHI decreased from 38.7 to 28.5 events per hour with trazodone, showing significant improvement compared to a placebo. Trazodone also helps people stay asleep longer by increasing the arousal threshold, meaning they wake up less often due to breathing problems. These findings suggest that trazodone could be a promising treatment for OSA without worsening oxygen levels. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Obstructive Sleep Apnea (OSA), particularly those who wake up too early during an obstructive event, preventing their airway muscles from responding properly. Specific eligibility criteria are not provided.

Inclusion Criteria

I have moderate-to-severe sleep apnea.

Exclusion Criteria

Hypersensitivity to the study drug (angioedema or urticaria)

Severe claustrophobia

I do not have major neurological disorders, heart failure, or other unstable conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo two overnight home sleep studies: one with trazodone and one with placebo, separated by a one-week washout period

2 weeks

2 visits (home-based)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Trazodone

Trial Overview The study tests the effect of Trazodone Hydrochloride, a medication given before sleep, on OSA severity and traits compared to a placebo. The goal is to see if Trazodone can improve sleep quality in OSA patients.

How Is the Trial Designed?

Group I: Trazodone Experimental Treatment 1 Intervention

Trazodone capsule 30 min before sleep

Group II: Placebo Placebo Group 1 Intervention

Placebo capsule 30 min before sleep

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Trazodone is an effective antidepressant for major depressive disorder (MDD) that not only alleviates depression symptoms but also effectively treats insomnia, a common issue in depression, with a favorable side effect profile compared to traditional SSRIs.

The new once-daily formulation of trazodone maintains stable blood levels for 24 hours, reducing side effects and improving treatment adherence, while its low incidence of weight gain and sexual dysfunction makes it a suitable option for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of trazodone in treatment of major depressive disorder: an update. Fagiolini, A., González-Pinto, A., Miskowiak, KW., et al.[2023]

The combination of atomoxetine and trazodone (Ato-Trazo) significantly reduced the apnea-hypopnea index in patients with obstructive sleep apnea (OSA), indicating improved severity of the condition, with a reduction from 18.2 to 7.4 events per hour (P = .024).

Unlike previous treatments, Ato-Trazo did not lower the arousal threshold, suggesting it may be better tolerated by patients, although it worsened self-reported sleep quality and further studies are needed to optimize dosage and identify the best patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway. Corser, B., Eves, E., Warren-McCormick, J., et al.[2023]

In a study involving seven patients with insomnia caused by the MAO-A inhibitor brofaromine, trazodone significantly improved deep sleep and altered sleep architecture, leading to subjective reports of better sleep quality.

Trazodone was found to be safe with minimal side effects and showed no negative interactions with brofaromine, suggesting it may be an effective treatment for insomnia related to MAO-I use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of trazodone on sleep disturbances induced by brofaromine. Haffmans, PM., Vos, MS.[2022]

In a study of 18 adults with obstructive sleep apnea (OSA), the combination of atomoxetine and trazodone significantly reduced the apnea-hypopnea index (AHI) and improved other sleep parameters compared to placebo, indicating better respiratory function during sleep.

The A-T combination also led to fewer apneas, less oxygen desaturation, and reduced respiratory arousals, suggesting it could be a viable alternative treatment for patients who struggle with standard OSA therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of atomoxetine and trazodone combination on obstructive sleep apnea and sleep microstructure: A double-blind randomized clinical trial study. Shahbazi, M., Heidari, R., Tafakhori, A., et al.[2023]

In a study involving 9 patients with obstructive sleep apnoea, trazodone at 100 mg significantly increased the arousal threshold during sleep, allowing patients to tolerate higher levels of carbon dioxide (CO2) before waking up.

The results suggest that trazodone may help improve breathing stability during sleep in OSA patients by increasing the effort-related arousal threshold, which could be beneficial for managing their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone increases arousal threshold in obstructive sleep apnoea. Heinzer, RC., White, DP., Jordan, AS., et al.[2021]

Clinically significant levels of m-CPP, a harmful metabolite of trazodone, are consistently found in patients using trazodone for sleep, indicating potential safety concerns.

The risks associated with m-CPP, including serious adverse effects, outweigh the benefits of trazodone, especially considering the availability of safer alternatives developed since the 1980s.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone. Kast, RE.[2015]

In a study involving 7 patients with obstructive sleep apnea (OSA), trazodone was found to increase the respiratory arousal threshold by 32%, suggesting it may help some patients with a low arousal threshold during sleep.

Despite this increase in arousal threshold, trazodone did not significantly change the apnea-hypopnea index or affect upper airway muscle activity and collapsibility, indicating that while it may offer some benefit, it is not enough to fully address the anatomical challenges of OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Eckert, DJ., Malhotra, A., Wellman, A., et al.[2021]

Trazodone is an effective antidepressant that works primarily by inhibiting serotonin reuptake, showing comparable efficacy to standard antidepressants in various double-blind trials involving both inpatients and outpatients.

It has a favorable safety profile with minimal anticholinergic and cardiovascular side effects, making it a good option for patients with depression who also experience agitation, anxiety, or insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of USA controlled trials of trazodone in clinical depression. Feighner, JP., Boyer, WF.[2019]

Trazodone significantly improves sleep in patients with insomnia by increasing total sleep time and enhancing non-rapid eye movement stage 3 sleep, while also reducing the time it takes to fall asleep and the number of awakenings during the night, based on a meta-analysis of 11 randomized controlled trials involving 466 participants.

Despite its efficacy in improving sleep architecture, trazodone is associated with side effects such as increased daytime drowsiness and decreased appetite, indicating that it should be used cautiously in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis. Zheng, Y., Lv, T., Wu, J., et al.[2022]

In an 8-week study involving six depressed patients, trazodone significantly improved both depression symptoms and sleep quality, as measured by psychological evaluations and sleep monitoring.

Patients experienced a 44% reduction in sleep latency and a 14% increase in total sleep time, along with a notable improvement in sleep architecture, including a 153% increase in deep sleep (Stage IV).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. Scharf, MB., Sachais, BA.[2013]

In a study involving 12 female patients, trazodone significantly improved sleep quality by increasing total sleep time and sleep efficiency while reducing awakenings and light sleep stages after just 7 days of treatment.

Trazodone also showed a positive effect on depression symptoms, as indicated by a reduction in the Hamilton depression rating scale scores, making it an effective option for treating insomnia associated with antidepressant use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of trazodone on sleep in patients treated with stimulant antidepressants. Kaynak, H., Kaynak, D., Gözükirmizi, E., et al.[2022]

Citations

1. publications.ersnet.org publications.ersnet.org/content/erj/31/6/1308

Trazodone increases arousal threshold in obstructive sleep ... Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4418332/

Trazodone Effects on Obstructive Sleep Apnea and Non-REM ... For the primary outcome, trazodone reduced the AHI when compared with placebo (38.7 ± 6.2 vs. 28.5 ± 5.6 events/h, P = 0.041; Table 1, Figure 1), without ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01817907

The Effects of Trazodone on Sleep Apnea Severity Previous data have shown that the non-myorelaxant hypnotic trazodone increases the arousal threshold however its effects on sleep apnea severity remain unclear.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25719754/

Trazodone Effects on Obstructive Sleep Apnea and Non-REM ... Conclusions: These findings suggest that trazodone could be effective therapy for patients with OSA without worsening hypoxemia.

5. thorax.bmj.com thorax.bmj.com/content/80/9/641

Effect of viloxazine and trazodone in obstructive sleep ... Conclusions Viloxazine-trazodone reduced OSA severity. Potential deleterious effects of viloxazine on sleep quality appeared partly attenuated by trazodone.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04162743

Study Details | NCT04162743 | The Effect of Trazodone on ... The investigators hypothesize that trazodone does not worse nocturnal oxygen saturation in insomnic ischemic stroke patients with obstructive sleep apnea (OSA) ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40360261/

Effect of viloxazine and trazodone in obstructive sleep ... Viloxazine-trazodone reduced OSA severity. Potential deleterious effects of viloxazine on sleep quality appeared partly attenuated by trazodone.

8. mdpi.com mdpi.com/1648-9144/58/2/225

Overview of the Role of Pharmacological Management ... A study looked at the effect of trazodone 100 mg in OSA patients with a low arousal threshold and found that it significantly increased the respiratory arousal ...