Talking Sleep

Live from SLEEP 2026: The Future of Sleep Pharmacotherapy

In this special live episode recorded from the SLEEP 2026 annual meeting in Baltimore, host Dr. Seema Khosla welcomes Dr. Sanjay Patel, director of the clinical sleep program at University of Pittsburgh Medical Center, to discuss groundbreaking medications for sleep disorders poised for FDA approval in 2026 and 2027.

The pharmaceutical landscape for sleep medicine is undergoing unprecedented transformation. Dr. Patel surveys the emerging drug pipeline that will fundamentally change how clinicians treat obstructive sleep apnea, narcolepsy, and idiopathic hypersomnia.

For obstructive sleep apnea, Dr. Patel discusses AD-109 (atomoxetine and R-oxybutynin), explaining the mechanistic rationale and practical considerations including use with tirzepatide. The Incannex drug combining dronabinol and acetazolamide receives analysis for different patient populations, and sultiame is discussed as a carbonic anhydrase inhibitor option. A critical framework emerges: Should treatment be symptom-based or airway-focused when PAP-intolerant patients present?

Tirzepatide, the GLP-1 agonist FDA-approved for moderate-to-severe OSA, receives comprehensive coverage including muscle loss concerns, long-term use, and emerging oral GLP-1 options. Retatrutide, the triple-hormone agent combining GLP-1, GIP, and glucagon, is also discussed.

The episode's most exciting segment focuses on orexin agonists for narcolepsy. Three pharmaceutical companies—Alkemeres, Centessa (purchased by Lilly), and Takeda—are developing these mechanistically novel agents. Dr. Patel clarifies how these medications differ, discusses why one medication disrupted nocturnal sleep (suggesting continued roles for oxybates), and addresses how clinicians will choose between similar medications.

Dr. Patel emphasizes a fundamental question: Should the field prioritize symptom management versus airway patency for OSA, and mechanistic approaches versus symptom management for narcolepsy?

Whether you're interested in emerging OSA treatments, narcolepsy innovations, or the future of pharmacological sleep medicine, this live episode provides essential updates on medications that will soon reshape clinical practice.

Join us for this exciting conversation about how sleep medicine will transform in the coming years.

Fixed PAP vs APAP: Impact on Blood Pressure and Autonomic Response

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Abhishek Goyal, Professor and Head of Respiratory Medicine in Dehradoon, India, and Dr. Prakhar Agarwal, a pulmonologist in private practice in Bhopal, India, to discuss their research comparing fixed CPAP versus auto-titrating CPAP (APAP) on blood pressure control and autonomic nervous system response.

For years, difficult-to-treat hypertension has been recognized as an indication for sleep studies, reflecting the assumption that treating sleep apnea improves blood pressure. But does the method of PAP therapy matter? Beyond achieving a residual AHI under 5, are there treatment nuances that could optimize cardiovascular outcomes? Dr. Goyal and Dr. Agarwal's research addresses these questions, building on landmark work by Dr. Pepin examining fixed versus auto-titrating PAP therapy.

The motivation includes both clinical and economic considerations. A 2021 Portuguese study examined cost implications, and similar economic pressures exist in India where APAP is significantly more expensive than fixed CPAP. The study used a crossover design comparing fixed CPAP to APAP, measuring blood pressure dipping patterns and autonomic response to assess cardiovascular effects.

The results have prompted Dr. Goyal to reconsider his clinical practice regarding pressure selection, raising important questions: If fixed CPAP offers superior blood pressure outcomes, should the standard practice of prescribing APAP devices be reconsidered? This challenges assumptions about adaptive algorithms and raises questions about prioritizing cardiovascular outcomes beyond AHI reduction.

The episode contextualizes these findings within India's unique healthcare landscape, exploring surprising OSA incidence data and examining whether craniofacial anatomy or arousal patterns differ from Western populations. Dr. Agarwal discusses how pressures are typically determined and the practical differences between APAP 4-20 versus narrow-range settings.

Whether you're prescribing PAP therapy for hypertension, optimizing cardiovascular outcomes, or seeking evidence-based approaches to pressure selection, this episode provides important international perspectives.

Join us for this discussion that may prompt reconsideration of how we set PAP pressures and what outcomes we should prioritize.

Insomnia Combination Treatment: New AASM Guidelines

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Daniel Buysse and Dr. Todd Arnedt, both members of the AASM clinical practice guideline committee, to discuss the newly released guidelines on combination treatment for chronic insomnia disorder in adults.

Unlike previous guidelines, this new guidance specifically addresses what happens in real-world clinical practice: patients often request both cognitive behavioral therapy for insomnia (CBT-I) and pharmacotherapy, or arrive seeking medications while clinicians advocate for behavioral interventions. The guidelines provide evidence-based recommendations for navigating these combination treatment scenarios, incorporating patient preferences in ways previous guidelines did not.

The conversation explores the guideline development process, including how committee members were selected and how diverse professional backgrounds enriched the discussion. Dr. Buysse and Dr. Arnedt explain why patient preference wasn't adequately reflected in original practice guidelines and how this updated version addresses that gap.

The first recommendation receives detailed examination: In adults with chronic insomnia, the AASM suggests combination treatment with CBT-I plus medication over medication alone (conditional recommendation, low certainty of evidence). The experts clarify which medications were examined, including whether dual orexin receptor antagonists (DORAs) were included, and explain why evidence certainty is low despite numerous studies. Pharmaceutical sponsorship creates methodological differences—PSG outcomes, fixed time in bed requirements—that complicate interpretation. The high placebo response in insomnia trials adds another layer of complexity.

Critical implementation questions arise: What does "combination therapy" actually mean? Should both treatments start simultaneously, or should one precede the other? Can patients start medications while awaiting CBT-I appointments given typical access delays?

The second recommendation appears paradoxical: The AASM suggests against combination treatment over CBT-I alone, yet recommends combination over medication alone. Dr. Buysse and Dr. Arnedt explain this nuanced position—CBT-I alone remains superior, but for patients who prioritize rapid total sleep time improvement over daytime symptom reduction, combination therapy may be reasonable.

The conversation addresses whether treatment order matters and whether clinical (not just insurance-driven) logic suggests a medication hierarchy—zolpidem before eszopiclone, the role of trazodone, when to consider ramelteon. A crucial question emerges: What about patients who refuse or cannot access CBT-I? How do these guidelines apply when the preferred behavioral treatment is unavailable or unwanted?

Throughout, the experts emphasize that guidelines inform but don't dictate clinical decisions. Patient preferences, values, and individual circumstances must shape treatment plans. The guidelines provide evidence-based frameworks while acknowledging the complexity of real-world insomnia management.

Whether you're treating chronic insomnia, navigating patient requests for medications, addressing CBT-I access barriers, or seeking evidence-based approaches to combination therapy, this episode provides essential guidance.

Join us for this important conversation about balancing behavioral and pharmacological approaches to chronic insomnia in clinical practice.

OSA and Parkinson’s Risk: Can CPAP Change Outcomes?

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Lee Neilson, Assistant Professor of Neurology at the University of Iowa and staff neurologist at the Iowa City VA specializing in movement disorders, to discuss his groundbreaking research examining whether obstructive sleep apnea represents a modifiable risk factor for Parkinson's disease.

Dr. Neilson's ambitious study analyzed records from 13 million patients within the VA system to investigate whether OSA is associated with higher risk of neurodegenerative disorders and whether treating sleep apnea might help delay the onset of dementia. The conversation traces the research design from initial hypothesis through methodology, explaining how he narrowed this massive dataset and defined both OSA diagnosis and Parkinson's disease progression.

Critical methodological details emerge: How was OSA diagnosed—through sleep testing, and using 4% or 3% hypopnea criteria? How did the study differentiate between mild and severe sleep apnea? How was Parkinson's disease identified—through clinical notes, medication records, or longitudinal follow-up? Dr. Neilson clarifies whether the analysis included only PD or extended to other neurodegenerative disorders like Alzheimer's disease.

The core findings receive extensive examination: Did CPAP therapy have a modifying effect on PD risk? After adjusting for confounding factors including BMI, diabetes, depression, and hypersomnia, which variables mattered most? What was the number needed to treat to prevent one case of Parkinson's disease? Could hypoxic burden be examined as a potential mechanism?

Intriguing tangential discussions explore whether idiopathic RBD can be distinguished from trauma-related RBD and whether these represent separate pathological processes. The conversation takes an unexpected turn into the neuroprotective effects of smoking in Parkinson's disease, with Dr. Neilson explaining proposed mechanisms and drawing parallels to ischemic preconditioning that might occur with OSA.

The episode addresses severity gradients—did OSA severity correlate with PD risk? It also tackles a fundamental question: Does treating sleep apnea delay dementia onset or actually prevent it? Dr. Neilson discusses whether non-PAP therapies were examined and addresses a critical ethical concern in sleep apnea research: Is it irresponsible to withhold treatment from symptomatic patients, and did this study focus on non-sleepy individuals or include all OSA patients regardless of symptoms?

This research has profound implications for how sleep medicine practitioners frame the importance of OSA treatment with patients and families. Beyond addressing immediate symptoms like sleepiness, treating sleep apnea may reduce long-term neurodegenerative risk—a compelling motivation for adherence that extends beyond quality of life to disease prevention.

Whether you're counseling patients about the importance of OSA treatment, interested in the sleep-neurodegeneration connection, or seeking evidence-based approaches to discussing long-term benefits of therapy, this episode provides essential insights.

Join us for this important conversation about how the work sleep medicine practitioners do every day may profoundly impact patients' neurological futures.