A new trial will measure popular sleep medications to better manage insomnia
A new Penn sleep study will test five popular sleep medications to give doctors better-informed treatment options.
Can’t sleep? You’re not alone.
Google Search trends for “sleep supplements” continue to rise as people reach for remedies—from melatonin to magnolia bark tea—to help them get a better night’s rest. Roughly one in three U.S. adults report short sleep duration, and about one in 10 meet the criteria for chronic insomnia. Americans now spend billions each year on over-the-counter sleep aids and supplements—often with little evidence to show which ones work, which don’t, and which might even cause harm.
So how can someone safely navigate this crowded marketplace of pills, teas, and supplements to find something that actually helps?
A new study, led by Richard Schwab, MD, Penn Medicine’s chief of Sleep Medicine, and Michael Perlis, PhD, director of Penn’s Behavioral Sleep Medicine program, seeks to provide some long-needed answers. The research team is studying how well different medications work and developing guidelines to help doctors treat insomnia, one of the most common and often misunderstood sleep problems.
Unlike most previous studies that focused on a single drug or highly controlled lab conditions, this trial will rely on a comparative effectiveness research (CER) model—meaning it will test how medications perform under real-world conditions. That’s important, because insomnia is most often diagnosed and treated in primary care settings, not sleep clinics.
The trial will compare five medications—trazodone, zolpidem (Ambien), doxepin, melatonin, and diphenhydramine (Benadryl)—against a placebo in more than 1,000 patients recruited from primary care practices across the University of Pennsylvania Health System.
Participants who do not respond to these medications will then have the opportunity to receive cognitive behavioral therapy for insomnia (CBT-I) at no cost. The study’s ultimate goal is to provide clear, evidence-based guidance to help both physicians and patients make better choices about insomnia treatment.
Asking foundational questions
The idea, according to Perlis, is to step back and address some of the most basic yet crucial questions in sleep medicine.
“There is an urgent need to know which drugs are best and safest for most conditions,” Perlis said. “For insomnia, the real question is where to start—what’s the best first step for the average patient who walks into their primary care doctor’s office saying they can’t sleep?”
Perlis notes that this particular study is unique in its size, scope, and approach. By emphasizing real-world treatment scenarios rather than laboratory sleep studies, the team hopes to generate data that directly reflect how these medications work in everyday life.
Schwab added that this design will also maximize the chances that participants find an effective treatment.
“If none of the medications are found to be effective, patients will have the option to receive cognitive behavioral therapy for insomnia,” Schwab said. “That way, everyone in the study gets access to something that has the potential to improve their sleep.”
Why primary care is key
Sleep issues rarely exist in isolation. According to Jeffrey Millstein, MD, regional director of Primary Care at Penn and a clinical assistant professor of Internal Medicine, insomnia often shows up alongside other health concerns such as depression, anxiety, chronic pain, tinnitus, and stress.
“We often begin with behavioral or ‘sleep hygiene’ suggestions, but the clinical conversation often ends up addressing medication options,” Millstein said.
If implemented, the study findings could give doctors the ability to make quicker and more evidence-based decisions in real time.
“Down the line, it would be great to use this data to create an electronic health record (EHR) decision tool for primary care providers to use during patient visits,” Millstein added.
CBT-I as an option
CBT-I is an offshoot of cognitive behavioral therapy (CBT), the treatment framework originally developed by the late Penn psychiatrist Aaron Beck, MD.
Unlike traditional CBT, CBT-I focuses specifically on sleep and uses structured behavioral changes to help people reset their sleep cycles. Perlis, one of the first to standardize and promote clinician training in CBT-I, describes the process as being “akin to rebooting one’s computer when the program runs awry.”
While CBT-I is recommended by most professional societies as the first-line treatment for chronic insomnia, many patients prefer to start with medication—and, in some cases, benefit from it. Some drugs are designed specifically for sleep, while others were developed for different conditions but appear to help certain patients with insomnia.
“The goal of our study is to find out which of these medicinal approaches are best, safest, and preferred by patients,” Perlis said. “Our study goes beyond assessing what makes for better nights—it also drills down on what makes for better days.”
Sharing results widely
The project, funded by the Patient-Centered Outcomes Research Institute (PCORI), will engage patients, doctors and policymakers to ensure the findings are easy to understand and put into practice.
“Working with PCORI requires that investigators expand their horizons and think differently about these diverse audiences,” Perlis explained. “That’s a centerpiece of this work—and it should have a significant impact on how the results are shared and implemented.”
Schwab added that many of the questions this research seeks to answer have puzzled the field of sleep medicine for decades.
“This study holds the promise of ushering in a new era of evidence-based treatment for patients with insomnia,” Schwab said. “If successful, it could make the current reality—of confusion and trial-and-error in sleep care—just another bad dream.”
To learn more about the study or how to participate, visit www.sleeplessinphilly.com.