Clinical Update

Medication Monitoring in a Changing Opioid Prescribing Landscape

The new 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain is an update to the most recent practice guideline published in 2016.1,2 The new recommendations address the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. Each of these areas is undeniably pivotal upon toxicology testing, and Recommendation 10 specifically focuses on the utilization of toxicology testing for the purpose of identifying prescribed and non-prescribed medications and controlled substances. The appropriate utilization of toxicology testing can significantly improve clinical outcomes and reduce the risk for adverse events, including overdose, in individuals suffering from pain.1,3,4,5,6

Baseline testing before initiation or dose titration of an opioid, or any nonopioid pharmacologic agent, may increase safety and decrease the risk of drug interactions or duplicate therapies.1,3,4,5,6,7,15 Electronic health records (EHR) and medication lists provided by patients are often incomplete, especially if the individual is hiding illicit or novel psychoactive substance (NPS) use.3,4,5,6,8 Aegis’s NPS testing offerings are developed to allow providers the ability to more completely identify unregulated substance use and afford them the opportunity to provide more informed care and minimize the potential for adverse events, including overdose deaths. Aegis is committed to a regular review of the NPS testing menu, which involves the addition of analytes newly circulating, as well as the deletion of analytes no longer circulating in the illicit drug supply in efforts to maintain a relevant test offering. Reports continue to demonstrate when drugs are purchased outside of a legitimate pharmacy, patients may be truly unaware of what they have ingested as many of these substances are contaminated with unknown products.5,9,10,14 Non-prescribed and illicit substance use have the potential for misuse, can be life-threatening, and can contribute to adverse effects when co-ingested with prescription opioids.3,11,12,13,14,15 Testing should be used to monitor and establish adherence and should intensify with initiation and with increasing opioid doses as the risk for opioid-related harms increases.1,3,6,15,16,17

In view of opioid prescribing, the escalating national crisis of fentanyl-related overdoses and synthetically manufactured compound use and the drug interactions that can result, it is important to understand the differences between toxicology testing methods to provide proper monitoring, effective intervention, safer prescribing, and improved clinical outcomes.3,4,5,6,15 Presumptive testing, otherwise known as immunoassay or point of care testing, can be combined with careful patient assessment when there is a priority to have more immediate results, even though substances may cross-react, leading to false positives and/or false negatives. Limited menus can preclude recognition of substances that may cause harm or serious adverse effects with prescribed opioids.3,4,6,18,19,20 To the contrary, definitive testing utilizes chromatography and mass spectrometry methods which result in accuracy specific to the substance tested and allows for differentiation between specific molecules identifying parent in addition to metabolite. For example, with fentanyl and fentanyl-analogues, the lab can differentiate these substances based on the differences in their respective molecular structures and where the atoms are located on each molecule. Definitive testing is designed to greatly minimize the potential for a false positive or false negative and is capable of detection with quantification.3,4,6,18,20 At Aegis, all positive results undergo definitive testing prior to reporting, and we are committed to employing the best available technology to optimize quality and accuracy of our laboratory testing, while continuing to provide a continually expanding testing menu and meeting realistic turn-around time expectations. Toxicology testing is recommended to accurately assess the risk of opioid-related harm.1,3,4,5,6,7

Aegis is not an advocate of toxicology results being used punitively against patients, but rather as a supportive tool to assist the clinician and patient in finding clarity together, using objective data. Dismissal could have adverse consequences for patient safety, potentially including the patient obtaining opioids or other drugs from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder.1,3,4,6,8,16 Aegis recommends incorporating state and federal regulations and regulatory requirements into clinical care planning to provide objective assessment of medication compliance, prescription drug misuse, illicit substance use, and the risk of drug diversion.3,5,6,7,17 Clinical care decisions and patient risk assessments cannot be based on the provider’s feelings, an individual’s appearance, or the individual’s socioeconomic status, but rather using guideline recommendations, the individual’s history, and current presentation.1,3,4,5,6,16 Results suggesting opioid or substance misuse should be discussed with the individual with a positive, supportive approach and significant or unexpected results should be reviewed with the testing laboratory.1,3,4 Drug testing should not be the sole determinant of an individual’s substance use but should be supplemented with conversations concerning medication use, the individual’s self-report of medications taken, and an assessment of monitoring methods.1,4,6 Treatment plans recommended by multiple guidelines can establish the two-way communication between provider and patient and can serve as an ongoing monitoring tool for compliance with terms for changes in risk status. Results of drug testing can also be used to help guide referral protocols as unexpected positive results may indicate a need for a higher level of care.1,3,4,5,6,16

Clinical drug test results play a pivotal role in patient diagnosis and treatment for pain. Patients and physicians depend on these results with the expectation that the data presented are complete, quality-driven, accurate, and reliable.1,3,4,5,6 Aegis recognizes the need for quality care, and we are committed to offering a test menu that is responsive to the needs of patients and the clinicians who care for them.


NOTICE: The information above is intended as a resource for health care providers. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct.



1. Dowell D, Ragan K, Jones C. CDC clinical practice guideline for prescribing opioids for pain – United States,2022. MMWR Morb Mortal Wkly Rep. 2022;71(3):1-95.
2. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain – United States,2016. MMWR Morb Mortal Wkly Rep. 2016;65(1):1-49.
3. American Association for Clinical Chemistry (AACC). AACC Academy: Laboratory Medicine Practice Guidelines. Washington, DC: American Association for Clinical Chemistry (AACC); 2018. Accessed Nov 21, 2022
4. Substance Abuse and Mental Health Services Administration. A Treatment Improvement Protocol: Managing Chronic Pain in Adults with or in Recovery from Substance Use Disorders: Tip 54. Rockville, MD: US Department of Health and Human Services; 2012. Accessed Nov 21, 2022.
5. Resource guide: screening for drug use in general medical settings. National Institute on Drug Abuse website. Updated March 2012. Accessed Nov 21, 2022.
6. Guidelines for the chronic use of opioid analgesics. Federation of State Medical Boards (FSMB) website. globalassets/advocacy/policies/opioid_guidelines_as_adopted_april-2017_final.pdf. Updated April 30, 2017. Accessed Nov 21, 2022.
7. Manchikanti L, Kaye AM, Knezevic HH, et al. Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) guidelines. Pain Physician. 2017;20(S3-92):1533-3159.
8. Argoff CE, Alford DP, Fudin J, et al. Rational urine drug monitoring in patients receiving opioids for chronic pain: consensus recommendations. Pain Med. 2018;19(1):97-117.
9. One Pill Can Kill. Drug Enforcement Administration. Accessed Nov 21, 2022.
10. 2020 National Drug Threat Assessment. Drug Enforcement Administration. Published March 2021. Accessed Nov 21, 2022.
11. Graves JM, Dilley J, Kubsad S, Liebelt E. Notes from the Field: Phenibut Exposures Reported to Poison Centers — United States, 2009–2019. MMWR Morb Mortal Wkly Rep 2020;69:1227–1228. DOI:
12. Tianeptine. Drug Enforcement Administration. Last Updated May 2019. Accessed Nov 21, 2022.
13. Xylazine. Drug Enforcement Administration. Last Updated February 2021.   Accessed Nov 21, 2022.
14. Drug Overdose Deaths. Centers for Disease Control and Prevention. Last Reviewed June 2, 2022. Accessed Nov 21, 2022.
15. Schrecker J, Puet B, Hild C, Schwope DM. Characterization of drug-drug interactions in patients whose substance intake was objectively identified by detection in urine. Expert Opin Drug Metab Toxicol.2018;14(9):973-978. doi:10.1080/17425255.2018.1509953
16. Jarvis M, Williams J, Hurford M, et al. Appropriate use of drug testing in clinical addiction medicine. J Addict Med. 2017;11(3)163-173.
17. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2):113-130.
18. Gourlay DL, Heit HA, Caplan YH. Urine Drug Testing in Clinical Practice: The Art and Science of Patient Care. 6th ed. Stamford, CT: PharmaCom Group, Inc.; 2015:1-32.
19. Heltsley R, DePriest A, Black DL, et al. Oral fluid drug testing of chronic pain patients. I. Positive prevalence rates of licit and illicit drugs. J Anal Toxicol. 2011;35:529-40.
20. Mickel C, Almazan P, West R, et al. LC-MS/MS extends the range of drug analysis in pain patients. Ther Drug Monit. 2009;31(6):746-8.