Digital pill biosensors for monitoring opioid medication use

In a research paper published in the Anesthesia & Analgesia, Brigham and women’s hospital investigators report on the results from a pilot study of 15 individuals who received a prescription to take oxycodone digital pills as needed following treatment for acute fractures.

Recently first digital pill was approved by the FDA for use with the antipsychotic drug Abilify, used to treat schizophrenia, bipolar disorder and depression. Opioids such as oxycodone are frequently prescribed on an as-needed basis for managing acute conditions, but uncertainty exists around how patients take the prescribed drug. Digital pills may offer a unique window into patterns of medication usage.

To conduct their pilot study, the investigators approached 26 individuals in the Emergency Department who had been diagnosed with an acute fracture. (Fifteen completed the study.) The team instructed participants to use oxycodone (one to two 5-mg oxycodone digital pills every six to eight hours) as needed for pain. Unused pills were returned after seven days.

The team used the eTectRx ID-Cap system. Each pill in the system consists of a unique radiofrequency emitter and a standard gelatin capsule containing an oxycodone tablet. When the capsule dissolves, the medication is released, and chloride ions energize the emitter. The patient wears a sticky patch on their abdomen, attached to a cable reader (the size of an iPod) that stores data about pill ingestion. (Since the study was conducted, advances in the technology have miniaturized the reader and added steps to validate the user of the system and provide directed feedback through a smartphone app.)

The digital pill system recorded a total of 112 ingestion events, compared to 134 ingestions based on pill count (84 percent accuracy). However, all missed ingestion events were traced back to two study participants who ingested digital pills without wearing the reader or did not interact with the reader due to severe pain. Most oxycodone doses were ingested within the first three days after discharge. On average, patients ingested only six pills, despite being given 21.

Citation: Chai, Peter R., Stephanie Carreiro, Brendan J. Innes, Brittany Chapman, Kristin L. Schreiber, Robert R. Edwards, Adam W. Carrico, and Edward W. Boyer. “Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.” Anesthesia & Analgesia 125, no. 6 (2017): 2105-112.
doi:10.1213/ane.0000000000002574
Funding: National Institutes of Health
Adapted from press release by Brigham And Women’s Hospital.

Research uncovers link between long-term opioid use and preexisting psychiatric and behavioral disease

A wide range of pre-existing psychiatric and behavioral conditions and the use of psychoactive drugs could be important risk factors leading to long-term use of opioid pain medications, reports a study in Journal Pain, the official publication of the International Association for the Study of Pain (IASP).

long term opioid addiction

Using a nationwide insurance database, the researchers identified 10.3 million patients who filed insurance claims for opioid prescriptions between 2004 and 2013. The study looked at whether pre-existing psychiatric and behavioral conditions and use of psychoactive medications were predictors of later opioid use.

“We found that pre-existing psychiatric and behavioral conditions and psychoactive medications were associated with subsequent claims for prescription opioids,” write Patrick D. Quinn, Ph.D., of Indiana University, Bloomington, and colleagues. The association appears stronger for long-term opioid use, and especially for patients with a previous history of substance use disorders.

The results also suggest that some outcomes viewed as harmful outcomes of opioid use substance use disorders, depression, suicidal or self-injuring behavior, and motor vehicle crashes are also predictors of which patients are at risk of long-term use of prescription opioids.

Overall, the results suggested a “modest” increase in any opioid prescriptions for patients with previous psychiatric or behavioral conditions (depression or anxiety disorders, opioid or other substance use disorders, suicide attempts or other self-injury, motor vehicle crashes, and sleep disorders) or use of psychoactive medications.

About 1.7 percent of patients with opioid prescriptions become long-term opioid users (six months or longer). But the risk became substantially higher for patients with mental health conditions or psychoactive medication use. Relative increases in rates of long-term opioid use ranged from 1.5 times for patients taking medications for attention-deficit/hyperactivity disorder, to about 3 times for those with previous substance use disorders other than opioids, to nearly 9 times for those with previous opioid use disorders.

Amid the continuing opioid epidemic, it’s important to understand which patients select (or are selected for) treatment with these pain medications. Previous studies have suggested a pattern of “adverse selection”: patients at greatest risk of harmful outcomes, including those with substance abuse and other psychiatric conditions, may be more likely to be prescribed opioids in higher doses and for longer durations.

Dr. Quinn and coauthors conclude: “Our findings support the ideas that clinical practice has deviated from the ‘careful selection’ under which most clinical trials are conducted and that thorough mental health assessment and intervention should be considered in conjunction with the use of long-term opioid therapy.

Citation: Quinn, Patrick D., Kwan Hur, Zheng Chang, Erin E. Krebs, Matthew J. Bair, Eric L. Scott, Martin E. Rickert, Robert D. Gibbons, Kurt Kroenke, and Brian M. D’onofrio. “Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims.” Pain 158, no. 1 (2017): 140-148.
DOI: 10.1097/j.pain.0000000000000730
Adapted from press release by Wolters Kluwer publications.

Researchers find that acupuncture produces natural opioid enkephalin which reduce high blood pressure in mice

Researchers with the UCI Susan Samueli Center for Integrative Medicine have found that regular electro-acupuncture treatment can lower hypertension by increasing the release of a kind of opioid in the brainstem region that controls blood pressure.

In tests on rats, UCI cardiology researcher Zhi-Ling Guo and colleagues noted that reduced blood pressure lasted for at least three days after electro-acupuncture by increasing the gene expression of enkephalins, which one of the three major opioid peptides produced by the body.

Their study, which appears in the Nature’s Scientific Reports, presents the first evidence of the molecular activity behind electro-acupuncture’s hypertension-lowering benefits.

Last year, the UCI team reported patients treated with acupuncture at certain wrist locations experienced drops in their blood pressure. The present study shows that repetitive electro-acupuncture evokes a long-lasting action in lowering blood pressure in hypertension, suggesting that this therapy may be suitable for treating clinical hypertension.

Hypertension affects about one third of the adult population of the world, and its consequences, such as stroke and heart attacks, are enormous public health problems, and the potential advantages of acupuncture over conventional medical therapy include few, if any, of side effects.

Citation: Li, Min, Stephanie C. Tjen-A-Looi, Zhi-Ling Guo, and John C. Longhurst. “Repetitive Electro-acupuncture Attenuates Cold-Induced Hypertension through Enkephalin in the Rostral Ventral Lateral Medulla.” Scientific Reports 6 (2016).
DOI: http://dx.doi.org/10.1038/srep35791
Adapted from press release by University of California Irvine