Laboratory Best Practice

SAFETY AND COMPLIANCE MONITORING OF PATIENTS RECEIVING CHRONIC OPIOID THERAPY

BACKGROUND
Patients receiving chronic opioid therapy (COT) should be randomly tested for elicit drug use and/or compliance with prescribed medications.¹ Recent guidelines recommend drug testing must be implemented from initiation and followed by subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. Urine drug testing serves as the primary specimen type for COT monitoring. Blood testing is usually not indicated. The purpose of urine drug testing is to verify adherence to prescribed medications, identify undisclosed drugs, and discourage drug misuse, abuse, and diversion. The goal of this Laboratory Best Practice article is describe current drug testing methods that are available for patients receiving COT.

DRUG TESTING TECHNIQUES
Drug testing methodology typically falls into one of two categories: (a) immunoassays, and (b) chromatographic and/or mass spectrometry techniques. Table 1 summarizes each method and their advantages and disadvantages.

Immunoassays: Immunoassays utilize specific antibodies to quickly (few hours) measure the presence of specific drugs (e.g., opioids, cocaine metabolites, barbiturates, amphetamines, and benzodiazapines). Like with any immunoassay technique, certain drugs may not be detectable despite structural similarities. For example, fentanyl is a commonly used synthetic opioid. Unfortunately, certain immunoassays may not be able to detect fentanyl due to its distinct (yet minute) structural differences compared to morphine or similar drugs. Alternately, other drugs may be misidentified due to these structural similarities (e.g., amphetamine vs. methamphetamine). Lastly, the sensitivity of immunoassays is dependent on their positivity cut-offs. In the case of opiates, immunoassay cut-offs may be as high as 300 or 2,000 ng/mL.^1,2 Due to these limitations, immunoassay results are typically qualitative in nature and require confirmation by higher order tests such as chromatography and/or mass spectrometry. Thus, the clinical utility of drug testing by immunoassay for COT is limited to being a first line, cost-effective, rapid screening tool for common compounds.

Chromatography and Mass Spectrometry: Chromatography (e.g., gas chromatography or liquid chromatography) and mass spectrometry provide both drug screening and confirmatory capabilities. Often, chromatography is combined with mass spectrometry to improve sensitivity. Both techniques can enable quantitative or qualitative differentiation of various compounds with good specificity. The sensitivity of combined liquid chromatography - mass spectrometry assays may be as low as 5 ng/mL for opioid/opiate testing, however in practice, most assays report can detect as low as 20 ng/mL since lower detection limits can increase false positive rates.³ Unfortunately, chromatography and mass spectrometry methods are time consuming (1-3 days), very expensive to operate, and can only detect drugs that have been validated by the institution. Not all institutions can test every drug (e.g., tramadol, buprenorphine), therefore, some tests may need to be sent to a reference laboratory.

Table 1. Comparison of Drug Testing Methods

Notes: *Some results may be qualitative due to assay performance.

BEST PRACTICES
Please refer to test performance information through the UC Davis Medical Center Test Directory (https://www.testmenu.com/ucdavis). Below are Laboratory Best Practices for screening of low- and high-risk patients, as well situations involving suspected drug overdose:

Compliance Monitoring in Low-Risk COT Patients: The first line screening should always include immunoassay testing. Clinicians are always advised to screen first with immunoassay and parallel with quantitative determination of known opioids/opiates by gas chromatography/mass spectrometry. Additional drugs testing for non-opioid/opiate compounds should be used judiciously and only when there is clinical suspicion of elicit drug use. Send out testing is also restricted and require clinical justification due to the large turnaround time (3-5 days) and substantial cost.

Compliance Monitoring in High-Risk COT Patients: As with low-risk patients, immunoassays should be the primary screening method and paralleled with opioid/opiate testing by gas chromatography and mass spectrometry. High-risk patients may present with socio-demographic factors, pain and drug-related factors, genetics and environment, psychosocial and family history, psychopathology, and alcohol and substance use disorders that should be evaluated.^2,4 These risk factors should be included in the clinical justification for ordering additional gas chromatography and mass spectrometry and/or send out tests.

Emergency / Overdose Cases: In patients with suspected overdose of either a known or unknown compound, screening by gas chromatography followed by mass spectrometry may be appropriate. Gas chromatography/mass spectrometry screening is also highly restricted and requires substantial clinical justification or ordering by the institution’s Medical Toxicology team. It must be noted that tests use for overdose work-up may not be suitable for COT monitoring. Overdose assays typically have higher cut-offs designed for this specific clinical setting.

REFERENCES

1. American Pain Society Guideline: “Use of Chronic Opioid Therapy in Chronic Noncancer patients: Evidence Review”. http://americanpainsociety.org/uploads/education/guidelines/ chronic-opioid-therapy-cncp.pdf, Accessed on, December 1, 2016.
2. Liebschutz JM, Saitz R, Weiss RD, et al. Clinical factors associated with prescription drug use disorder in urban primary care patients with chronic pain. J Pain 2010; 11:1047-1055.
3. American Association for Clinical Chemistry, Clinical Laboratory News Article: CLN Reader Survey Results on Pain Management Testing. https://www.aacc.org/publications/cln/articles/ 2016/november/cln-reader-survey-results-on-pain-management-testing. Accessed on December 1, 2016.
4. Sehgal N, Manchikanti L, Smith HS. Prescription opioid abuse in chronic pain: A review of opioid abuse predictors and strategies to curb opioid abuse. Pain Physician 2012;15:ES67-ES92.

See previous month's topic »