Patients undergoing clinical drug monitoring tested positive for a broad range of other unexpected medications; plus, a look at buprenoprhine and gabapentinoid drug-detection trends.

Pages 17-18

With Angela G. Huskey, PharmD, CPE

The following results stem from a report conducted by Millennium Health (San Diego, CA), titled Signals Report: National Drug Use Trends, which featured retrospective analyses of more than 5 million de-identified drug test results, starting in 2013 and leading up to 2018. The goal was 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, after the report was released in March 2019.

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). 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 timeframe (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 (MAT), naloxone, and fentanyl-specific messaging” in order to tackle fentanyl-spiked heroin.

Gabapentinoids

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 (SUD) 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. Only Kentucky, Michigan, and Tennessee have designated gabapentin as a Schedule V controlled substance; other states require reporting to prescription monitoring databases due to gabapentin’s abuse potential. At the federal level, pregabalin is a Schedule V controlled substance.

Millennium Health’s analysis of gabapentinoids included de-identified UDT results from August 4, 2014 through June 30, 2018. 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.

Unexpected Results

The frequency of unexpected results (positives for non-prescribed gabapentin) was: 12% in pain management; 13% in primary care practices; and 12% in addiction treatment centers. The frequency of unexpected results (positives for non-prescribed pregabalin) was: 1.60% in pain management; 75% in primary care practices; and 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 Millennium Health.

Buprenorphine/Naloxone

Buprenorphine and buprenorphine combination products such as Suboxone promise to reduce opioid cravings and withdrawal symptoms and are commonly used in 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 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.”

Millennium Health analyzed more than 150,000 de-identified UDT results for specimens from patients with reported prescriptions for Suboxone from July 1, 2017 to July 1, 2018. The analysis tested for 40 medications, illicit drugs, and drug metabolites using LC-MS/MS. Buprenorphine was detected in 95% of specimens; 2% of these positives revealed abnormally high concentrations of buprenorphine and little or no metabolites, suggesting that adulterations may have been performed.

Most Common Findings of Non-Prescribed Drugs

The five most commonly found non-prescribed or illicit drugs in the patient samples were: 23.3% marijuana; 11.4% gabapentin; 10.8% alcohol; 7.1% cocaine; and 5.8% methamphetamine. Medications typically avoided in patients prescribed buprenorphine/naloxone, including opioids and benzodiazepines, were frequently detected in samples from patients without a corresponding prescription, such as:

hydrocodone (1,508 positives, 98% lacked prescription)

oxycodone (2,685 positives, 96% lacked prescription)

benzodiazepines (6,003 positives, 70% lacked prescription)

fentanyl (5,415 positives, 99.9% lacked prescription).

Among those prescribed Suboxone, 4.4% tested positive for opiates such as codeine and/or morphine, and the heroin metabolite 6-acetylmorphine (6-AM) was present in 1.8% of specimens. Illicit drug combinations were also detected in a small percentage of samples.

Approximately 95% of specimens from patients with prescriptions for Suboxone had positive test results for buprenorphine. Benzodiazepines and alcohol were often detected; these substances are known to increase the risk of opioid-induced respiratory depression, overdose deaths, and may be an indication of relapse. Findings of fentanyl alone and in combination with heroin are most concerning since fentanyl is suspected to be linked to a recent increase in opioid mortality.

The analysis may be applied to better understand and assess risks of drug threats to those being treated with MAT. While previous studies have relied on immunoassay-based UDT, providing limited information, Millennium Health’s report provides the only known study to date looking at definitive test results in this manner.

“Both prescription drug monitoring programs and urine drug monitoring are recommended to be used by clinicians as part of an ongoing risk management approach when prescribing controlled substances, in combination with using risk screening tools, pill counts, patient education, informed consents, and referral to other types of providers when necessary,” Dr. Huskey said.

Editor's Note: See PPM's 2019 literature review and commentary series on current trends in Addiction Medicine and Relapse Prevention.

Last updated on: May 3, 2019

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