Recovery for Patients Prescribed Medications for OUD Jeopardized by Concurrent Polysubstance Use

While the use of medications has proven to be an effective strategy for treating opioid use disorder, practitioners must be aware of concurrent use of non-prescribed, illicit substances that can negatively impact treatment and potentially harm patients.

At the recent Cape Cod Symposium on Addictive Disorders, Kelly Olson, PhD, director of clinical affairs for Millennium Health, shared key considerations for monitoring patients’ medications within the context of a comprehensive treatment approach, and underscored the skills needed to identify and navigate polysubstance use challenges.

Shortly after her presentation in Hyannis, Massachusetts, Addiction Professional caught up with Dr Olson to discuss emerging drug trends, challenges with polysubstance use by patients who are receiving medication-assisted treatment for opioid use disorder, and tools that providers can use to address these issues and improve patient outcomes.

Editor’s note: This interview has been edited for length and clarity.

Addiction Professional: Based on urine drug testing results, what emerging drug trends are you seeing in recent months, particularly related to polysubstance use?

Kelly Olson: There are many noteworthy recent trends. As reported in the Millennium Health Signals Report, polysubstance use involving fentanyl has grown remarkably since 2015 and fentanyl co-detection increased by more than 60% from 2019 through 2022.

Fentanyl co-detection in those positive for the other primary drivers of overdose (methamphetamine, cocaine, heroin, prescription opioids) reached all-time highs in our database at the end of 2022. The co-detection of fentanyl had a 93% increase in specimens positive for prescription opioids and a 180% increase in those positive for methamphetamine since 2019. Fentanyl positivity among individuals who were positive for heroin in 2022 is over 95%. Nearly two-thirds of specimens that were positive for prescription opioids were also positive for fentanyl in 2022. Almost half of specimens positive for methamphetamine were also positive for fentanyl in 2022. Almost half (about 42%) of cocaine-positive specimens in 2022 were also positive for fentanyl.

Fentanyl analogue co-detection in fentanyl users remains high. Over 60% of specimens positive for fentanyl are also positive for one or more fentanyl analogues. But a geographical divide existed in late 2022. Acetyl fentanyl was found more commonly in the West, and parafluorofentanyl was found much more commonly in the East. This is no longer the case for parafluorofentanyl, a potent fentanyl analogue. As we’ve moved through the summer of 2023, we’ve noted a significant increase in parafluorofentanyl detections in the Pacific and Mountain regions. Clinicians in these areas should take be aware of this emerging threat, as it may increase overdose risk and complicate opioid use disorder treatment.

Xylazine is another emerging threat. Based on our unique database of definitive urine drug test results from individuals seeking healthcare, xylazine has now reached all regions of the country. Xylazine is almost always found with fentanyl; 99.9% of the time fentanyl is also present in that specimen. Nationally, 16% of fentanyl positive specimens are also positive for xylazine, but this number exceeds 30% in Pennsylvania, North Carolina, Ohio, and Maryland. Polysubstance use is very common in those using fentanyl and xylazine. This includes the use of other highly sedating drugs (benzodiazepines, alcohol, gabapentin) that, like xylazine, do not respond to naloxone, making for a dangerous situation for the user and a challenging one for the first responder.

AP: What issues should providers be aware of with regards to polysubstance use among patients receiving medications for opioid use disorder (OUD)?

KO: It’s an important question and one we have studied. In short, methadone and buprenorphine have proved themselves effective at reducing substance use, but use remains high.

In our study of patients prescribed buprenorphine for OUD, several key findings emerged. First, nearly half of patients (47.58%) showed positivity for nonprescribed substances, particularly for marijuana, benzodiazepines, and gabapentin. Buprenorphine positivity was consistently associated with lower positivity of all other substances except for gabapentin. Patient age and sex, setting of care, and geographic region were associated with drug positivity among patients prescribed buprenorphine, but the results varied by substance. For example, older patients, women, those with private insurance, and those being treated in primary care were more likely to have oxycodone positivity, whereas fentanyl positivity was highest among young men, those with Medicaid, those being treated at substance use treatment centers, and those living in New England.

Across our 5-year study period of those prescribed methadone, the first collected urine specimens indicated increasing fentanyl positivity rates—from 13.1% in 2017 to 53% in 2021. The positivity rate for methamphetamine also increased, from 10.6% to 27.2% as did cocaine, from 12.8% to 19.5%.

•          Fentanyl use declined from 21.8% to 17.1% over 52 weeks with methadone treatment.

•          Heroin use also declined, from 8.4% to 4.3%.

•          For both heroin and fentanyl, the biggest declines were seen in the first 10 weeks of treatment.

•          Methamphetamine and cocaine did not significantly change over the course of treatment.

We have concluded that patients are increasingly testing positive for fentanyl and other illicit drugs at the start of treatment. Patients significantly decrease their use of illicit opioids with methadone and buprenorphine treatment. But fentanyl use remains high as do cocaine and methamphetamine use. The findings clearly sound an alarm bell that we need more tools to support these patients particularly as it relates to other types of substance use.

We’ve also investigated buprenorphine “spiking”, the direct addition of prescribed buprenorphine to urine drug test specimens to mimic results suggestive of adherence. We found 7.6% of patients had evidence of buprenorphine spiking. Specimens suggestive of buprenorphine spiking were more likely to be positive for nonprescribed opioids and collected in primary care settings.              

AP: What are some key skills and tools to help providers identify and navigate scenarios involving polysubstance use among patients?

KO: Stay aware of emerging trends. At Millennium Health, it is more important than ever to do our part by informing public health surveillance efforts while bringing awareness to communities at increased risk. Sharing vital, timely information to help reduce overdose deaths is a critical component to a provider’s cache of skills and tools when discussing polysubstance use with their patients. Providers should use the surveillance we provide and other data (DEA seizure data, overdose reporting, etc.) to remain aware of trends.

Because of the threat of fake pills and other adulterated drug products, a patient may be unaware of all the substances they’re taking. It’s important to listen for clues that this may be happening. Do they report different or unique drug effects? Are they complaining of wound formation that may indicate the use of fentanyl adulterated with xylazine? Do they report the drug smelling or tasting different? Are any withdrawal symptoms new or unusual? All may be important clues.

Assessing the presence or absence of pharmaceuticals (e.g., medication monitoring) and/or illicit substances, via definitive urine drug testing, is of paramount importance, as again, many individuals may not even know they are using tainted drugs, and since there are no CLIA-waived point-of-care test for fentanyl, xylazine, fentanyl analogues, etc., definitive testing, may be more warranted than ever. Using definitive testing can also help clinicians obtain a clear picture of what a patient is using to inform the development of the patient’s treatment plan. Providers should know to be suspicious of spiking of buprenorphine and have a trusted toxicologist they can quickly and reliably reach to help with interpreting difficult cases.

Providers should be open to considering new treatment paradigms, i.e., the arrival of fentanyl to our communities has made the prescribing of buprenorphine more challenging in some cases. Precipitated withdrawal seems to be more common. Providers should remain open to reconsidering dosing strategies. They should also be open to using other harm reduction strategies, i.e., fentanyl test strips, if not already.

AP: Is there anything else you would like to add that we have not yet covered?

KO: Polysubstance use is the rule, not the exception. Over 80% of our fentanyl-positive specimens are positive for other substances. The frequency at which we find other substances depends largely on geography. Providers must remain aware of evolving trends. Today, xylazine and parafluorofentanyl have our attention. Tomorrow, who knows. We will continue to watch and report on trends as they happen through our Emerging Threat Intelligence program and with our many academic and government partners.

Reference

Olson K. Polysubstance use in patients prescribed medications for opioid use disorder: current evidence from urine drug testing to inform treatment planning. Presented at Cape Cod Symposium on Addictive Disorders. September 7-10, 2023; Hyannis, Massachusetts.