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Millennium Health Report on National Drug Use Trends

March 20, 2019
Patients undergoing addiction treatment with buprenorphine/naloxone tested positive for a broad range of other unexpected medications; plus, a look at gabapentinoid abuse & drug detection trends.
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With Angela G. Huskey, PharmD, CPE

The following are results from a report1 conducted by Millennium Health (San Diego, CA), featuring retrospective analyses of more than 5 million drug test results to mark trends and answer questions associated with medication use and substance abuse.

Non-Prescribed Fentanyl Co-Identified with Heroin

Urine drug testing (UDT) positivity rates for non-prescribed fentanyl among heroin-positive specimens has risen by 1,800% since 2013. In 2016, the CDC and DEA both issued nationwide warnings on the increased prevalence of illicit fentanyl, an action that prompted researchers to analyze results from UDTs and mark trends from a healthcare population initially from 2013 to 2017.

“Published literature has shown that self-report of medication and/or substance use is not always reliable, thus urine drug testing is considered an appropriate tool for providing clinicians with objective information regarding a patient’s recent use of certain medications and illicit substances, but [is] not able to help a clinician determine dose of the detected medication,” Angela G. Huskey, PharmD, CPE, senior vice president and chief clinical officer at Millennium Health, told PPM.

An analysis of over 5 million de-identified UDT results from January 1, 2013 through May 31, 2018, included specimens with tests ordered for definitive drug testing by liquid chromatography/mass spectrometry (LC-MS/MS) to detect the presence of 6-MAM (a heroin metabolite) and fentanyl (including testing for the parent drug and its metabolite norfentanyl). Specimens from patients with reported fentanyl prescriptions were excluded from the analysis.

Among test results that were heroin-positive, specimens from patients that did not have a reported fentanyl prescription but were positive for fentanyl were identified:

  • Nationally, 39% of specimens that tested positive for heroin were concomitantly positive for non-prescribed fentanyl in 2018; this percentage was only 2% in 2013
  • The number of heroin-only positive tests per year remained steady over the 5-year time frame (0.94% in 2013 and 1.15% in 2018)
  • Fentanyl-positive rates varied substantially by region of the US. In 2018, the proportion of specimens testing positive for heroin with non-prescribed fentanyl ranged from 5% in the Pacific region to 84% in the East South Central region. Fentanyl is found with heroin predominantly in more eastern regions of the US
  • The 10 states with the highest UDT positivity rates for heroin with non-prescribed fentanyl: Iowa, Kentucky, Maryland, Massachusetts, Maine, New Hampshire, Ohio, Connecticut, West Virginia, and Michigan.

Researchers noted in the report that these results may “inform and focus clinicians, first responders, and public health agencies to better leverage various modalities such as medication assisted addiction treatment, naloxone, and fentanyl-specific messaging” in order to tackle fentanyl-spiked heroin.

Added Dr. Huskey, “Clinicians need to be aware that patients presenting for care in any setting may have been exposed knowingly or unknowingly to these drug combinations.”

(Source: Millennium Health)


The CDC released a statement in 2016 recommending gabapentinoids (including gabapentin and pregabalin) as first-line treatment for neuropathic pain, while other reports have marked gabapentin as useful for comorbid substance use disorder and pain. In 2013, an estimated 44 million gabapentin prescriptions were dispensed, and by 2017, 68 million prescriptions were dispensed, making gabapentin the 10th most prescribed medication in the US.

However, studies have suggested that gabapentinoids may be misused or abused, either alone or in combination with opioids. In a July 2018 letter to the New England Journal of Medicine, for example, FDA identified gabapentinoids as a potential emerging threat. Only Kentucky, Michigan, and Tennessee have designated gabapentin as a Schedule V controlled substance, whereas some states require reporting to prescription monitoring databases due to gabapentin's abuse potential. Pregabalin, in addition, is a Schedule V controlled substance federally.

Millennium Health’s analysis included de-identified urine drug testing results from August 4, 2014 through June 30, 2018 for patient specimens submitted for testing by clinicians as part of therapeutic treatment. During this time period, the volume of reported gabapentin prescriptions showed an upward trend, whereas the percent of samples positive for non-prescribed gabapentin remained relatively stable. The analysis was performed using LC-MS/MS for specimens tested for either gabapentin or pregabalin. One limitation of the analysis was the reliance on accurate and complete reports of prescribed medications by the ordering clinician.

The frequency of unexpected results (positives for non-prescribed gabapentin) was:

  • 12% in pain management
  • 13% in primary care practices
  • 12% in addiction treatment centers.

The frequency of unexpected results (positives for non-prescribed pregabalin) was:

  • 1.60% in pain management
  • 0.75% in primary care practices
  • 0.18% in addiction treatment centers.

Despite the controversy surrounding the potential misuse and abuse of gabapentinoids, data in this report suggests that the percent of samples positive for gabapentin without a reported prescription, relative to the total number of prescriptions written, has remained relatively unchanged since 2014 on a national level, but does vary in some states.

The reported high prescription rates of gabapentinoids, the shift away from traditional opioid prescribing, as well as its supposed potential for abuse, warrant better monitoring and reporting of the opioid alternative overall, according to the Millennium Report.

Drug Detection with Buprenorphine/Naloxone

Buprenorphine and buprenorphine combination products such as Suboxone promise to reduce opioid cravings and withdrawal symptoms and are commonly used in medication-assisted treatment (MAT).However, those with opioid use disorder (OUD) may relapse by taking nonprescribed medications or illicit drugs. While UDT during treatment of OUD monitors the effectiveness of a patient’s treatment plan, studies have shown that self-report of medication and/or substance use can be unreliable, including among patients with substance use disorder (SUD).

“The frequency of drug testing should be determined by a number of factors, including the stability of the patient, time of abstinence, and treatment plan goals,” Dr. Huskey told PPM. “Patients will likely require more testing early in treatment or during periods of relapse. Once a patient is progressing well and has consistent negative drug tests, the frequency of random testing should be decreased accordingly.”

Last updated on: April 16, 2019
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