Posted on by Lawrence Tabak, D.D.S., Ph.D.
Opioid use disorders (OUD) now threaten the health and lives of far too many young and adult Americans. While getting treatment is a key first step to recovery, overcoming an opioid addiction often comes with brutal withdrawal symptoms, including bad bouts of insomnia that are often untreatable with traditional prescription sleep medications. These medications act as sedatives, making them unsafe for people in OUD recovery.
But now, researchers have found that an approved drug for insomnia that works differently than other sleep medications could offer some needed help for the sleeplessness that affects those overcoming an opioid addiction . The drug, known as suvorexant (Belsomra ®), was provided in a study to people during and immediately after tapering off opioids, and it allowed them to sleep significantly more during this week-long period. Suvorexant also helped to reduce their opioid withdrawal and craving.
This study, which received support from NIH’s Helping to End Addiction Long-term (HEAL) Initiative certainly offers promising news. The Food and Drug Administration (FDA) approved suvorexant to treat insomnia in 2014, and it is available for off-label use to help people overcoming an OUD.
The good news, however, comes with a major caveat. This early clinical trial had relatively small enrollment numbers, and larger studies are definitely needed to follow up and confirm the initial results.
The latest findings, published in the journal Science Translational Medicine, come from a team at Johns Hopkins University School of Medicine, Baltimore, led by Andrew Huhn. He and colleagues recognized sleep disturbances as a severe problem during recovery. They wondered whether suvorexant might help.
Suvorexant doesn’t actively sedate people like other sleeping medications. Suvorexant works by targeting orexin, a biochemical made in the brain that helps keep you awake . Interestingly, orexin signals also have been implicated in opioid withdrawal symptoms, sleep disturbances, and drug-seeking behaviors.
Thirty-eight people entered the Hopkins study, and 26 completed it. Their average age was about 40, with close to equal numbers of white and Black participants. Most were male, and all were undergoing supervised withdrawal treatment with buprenorphine/naloxone, which is used in combination as a medication-assisted treatment for OUD.
To find out if suvorexant helped, the researchers measured total sleep time nightly using wireless devices that recorded brain activity and movement in people taking either 20 milligrams or 40 milligrams of suvorexant versus a placebo. The researchers also used standard methods to assess symptoms of opioid withdrawal, along with suvorexant’s potential for abuse.
The data showed that people taking suvorexant over four days while tapering off opioids slept about 90 minutes longer per night on average. They also continued to sleep for an extra hour a night on average in the four days following the tapering period. The researchers note that these increases in sleep duration far exceed the American Academy of Sleep Medicine’s threshold for clinically meaningful improvement.
The researchers also didn’t see any differences in adverse events between those taking suvorexant versus a placebo. They also note that the main side effect of suvorexant in general is feeling sleepy the next day as the drug wears off slowly. There also wasn’t any evidence that suvorexant might come with a risk for drug abuse.
However, because the study was small, it lacked the needed statistical power to determine meaningful differences between the two doses of suvorexant. The study also didn’t include many women. But overall, the evidence that suvorexant or even other medications that target orexin could improve OUD treatment appears quite promising.
The NIH’s HEAL Initiative has launched over 600 research projects across the country. These studies cover a range of science and health care needs. But a common thread running through these projects is a desire to enhance the evidence base for lifesaving OUD interventions. Another is a commitment to discover better ways to help people recover from an OUD, and these latest data on suvorexant show this commitment in action.
 Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Huhn AS, Finan PH, Gamaldo CE, Hammond AS, Umbricht A, Bergeria CL, Strain EC, Dunn KE. Sci Transl Med. 2022 Jun 22;14(650):eabn8238.
 The hypocretin/orexin system. Ebrahim IO, et al. J R Soc Med. 2002 May;95(5):227-30.
SAMHSA’s National Helpline (Substance Abuse and Mental Health Services Administration, Rockville, MD)
Opioids (National Institute on Drug Abuse/NIH)
Andrew Huhn (Johns Hopkins School of Medicine, Baltimore)
NIH Support: National Institute on Drug Abuse
Posted on by Dr. Francis Collins
A few weeks ago, I was pleased to take part in the announcement of NIH’s HEALing Communities Study in four states hard hit by the opioid epidemic. This study will test a comprehensive, evidence-based approach—which includes the wide distribution of naloxone to reverse overdoses—with the aim of reducing opioid-related deaths in selected communities by 40 percent over three years.
That’s a very ambitious goal. So, I was encouraged to read about new findings that indicate such reductions may be within our reach if society implements a number of key changes. Among those is the need to arm friends, family members, and others with the ability to save lives from opioid overdoses. Between 2013 and 2016, nine states instituted laws that give pharmacists direct authority to dispense naloxone to anyone without a prescription. However, the impact of such changes has remained rather unclear. Now, an NIH-funded analysis has found that within a couple of years of these new laws taking effect, fatal opioid overdoses in these states fell significantly .
The misuse and overuse of opioids, which include heroin, fentanyl, and prescription painkillers, poses an unprecedented public health crisis. Every day, more than 130 people in the United States die from opioid overdoses . Not only are far too many families losing their loved ones, this crisis is costing our nation tens of billions of dollars a year in lost productivity and added expenses for healthcare, addiction treatment, and criminal justice.
Opioid overdoses lead to respiratory arrest. If not reversed in a few minutes, this will be fatal. In an effort to address this crisis, the federal government and many states have pursued various strategies to increase access to naloxone, which is a medication that can quickly restore breathing in a person overdosing on opioids. Naloxone, which can be delivered via nasal spray or injection, works by binding opioid receptors to reverse or block the effect of opioids. The challenge is to get naloxone to those who need it before it’s too late.
In some states, a physician still must prescribe naloxone. In others, naloxone access laws (NALs) have given pharmacists the authority to supply naloxone without a doctor’s orders. But not all NALs are the same.
Some NALs, including those in Alaska, California, Connecticut, Idaho, New Mexico, North Dakota, Oklahoma, Oregon, and South Carolina, give pharmacists direct authority to dispense naloxone to anyone who requests it. But NALs in certain other states only give pharmacists indirect authority to dispense naloxone to people enrolled in certain treatment programs, or who meet other specific criteria.
In the new analysis, published in JAMA Internal Medicine, a team that included Rahi Abouk, William Paterson University, Wayne, NJ, and Rosalie Liccardo Pacula and David Powell, RAND Corp., Arlington, VA, asked: Do state laws to improve naloxone access lead to reductions in fatal overdoses involving opioids? The answer appears to be “yes,” but success seems to hinge on the details of those laws.
The evidence shows that states allowing pharmacists direct authority to dispense naloxone to anyone have seen large increases in the dispensing of the medication. In contrast, states granting pharmacists’ only indirect authority to dispense naloxone have experienced little change.
Most importantly, the research team found that states that adopted direct authority NALs experienced far greater reductions in opioid-related deaths than states with indirect authority NALs or no NALs. Specifically, the analysis showed that in the year after direct authority NALs were enacted, fatal opioid overdoses in those states fell an average of 27 percent, with even steeper declines in ensuing years. Longer-term data are needed, and, as in all observational studies of this sort, one must be careful not to equate correlation with causation. But these findings are certainly encouraging.
There were some other intriguing trends. For instance, the researchers found that states that allow pharmacists to dispense naloxone without a prescription also saw an increase in the number of patients treated at emergency departments for nonfatal overdoses. This finding highlights the importance of combining strategies to improve naloxone access with other proven interventions and access to medications aimed to treat opioid addiction. Integration of all possible interventions is exactly the goal of the HEALing Communities Study mentioned above.
Successfully tackling the opioid epidemic will require a multi-pronged approach, including concerted efforts and research advances in overdose reversal, addiction treatment, and non-addictive pain management . As I’ve noted before, we cannot solve the opioid addiction and overdose crisis without finding innovative new ways to treat pain. The NIH is partnering with pharmaceutical industry leaders to accelerate this process, but it will take time. The good news based on this new study is that, with thoughtful strategies and policies in place, many of the tools needed to help address this epidemic and save lives may already be at our disposal.
 Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose. Abouk R, Pacula RL, Powell D. JAMA Intern Med. 2019 May 6
 Opioid Overdose Crisis. National Institute on Drug Abuse/NIH. Updated January 2019.
Naloxone for Opioid Overdose (National Institute on Drug Abuse/NIH)
NIH Support: National Institute on Drug Abuse