Role of Urine Drug Testing in the Current Opioid Epidemic : Anesthesia & Analgesia

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Chronic Pain Medicine

Role of Urine Drug Testing in the Current Opioid Epidemic

Mahajan, Gagan MD

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doi: 10.1213/ANE.0000000000002565
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Opioids represent one of many therapeutic options to treat chronic nonmalignant pain (CNMP) and have been among the most frequently prescribed medications in the United States since 1990s, with hydrocodone being the second most dispensed medication overall as of 2015.1–4 In 2015, clinicians in the United States prescribed 3 times the amount of opioids than they did in 1999 and 4 times the amount than their European counterparts did in 2015.5 The lack of alternative nonopioid medications to address moderate to severe CNMP that are equally efficacious yet safer than opioids partially explains the explosion in opioid prescribing for this population.6 Undoubtedly, the use of chronic opioid therapy (COT) in patients with CNMP remains controversial because of insufficient trials >12 months demonstrating analgesic and functional benefits, and mounting data that repeatedly highlight the (dose-dependent) hazards of COT: opioid misuse and abuse, opioid-related motor vehicle accidents, and unintentional death from overdosing.7–12 In the United States, current estimates indicate that 2 million people suffer from opioid addiction at an associated economic burden of $78.5 million annually.5 From 1999 to 2014, opioids have contributed to 165,000 fatal overdoses and, as a pharmaceutical class, have accounted for the greatest number of deaths from poisoning.12–14 According to the Centers for Disease Control and Prevention’s most recent data from 2015, of the 52,404 drug overdose deaths, 63.1% involved opioids.15 These opioid overdose deaths represent an 11.4% increase from the 28,647 deaths in 2014, with the increased percentage of deaths being predominantly from illicitly manufactured fentanyl and heroin.15 Challenges remain, however, on identifying the most effective solution that decreases the deadly risks associated with opioids while still maintaining access to this therapy for those who benefit from it.

For clinicians whose practice mostly consists of patients with chronic nonmalignant pain (CNMP), urine drug testing appears to be routine. Using a survey of urine drug testing practices of physicians of various specialties (eg, Anesthesiology, Family Medicine, Internal Medicine, Physical Medicine and Rehabilitation, Neurology, Orthopedic Surgery, Psychiatry, and Radiology, etc) who self-reported that 70%–100% of their patients had CNMP, Pergolizzi et al16 found that 82% of the physicians urine drug tested their patients. Even though numerous guidelines recommend urine drug testing, the behavior among primary care physicians (PCPs) in a traditional primary care practice may be starkly different.9 In their retrospective chart review, Adams et al17 found only 8% of PCPs urine drug tested their patients. Utilizing a written survey, Bhamb et al18 showed 7% of PCPs urine drug tested patients before starting COT and 15% of PCPs urine drug tested existing patients. Among primary care clinicians who did perform urine drug testing, physicians were more apt to order the test compared to nurse practitioners or physician assistants.19 The most common reasons why primary care clinicians performed urine drug testing included current substance abuse disorder, high-dose opioid therapy, and black race. The authors concluded these criteria reflected the unconscious biases and misconceptions of which patients were at risk for opioid abuse. In comparison, clinicians whose primary practice involved taking care of patients with CNMP most commonly performed urine drug testing in patients who were already on controlled substances, were potential candidates for COT, exhibited aberrant behavior, or requested specific drugs.16 Common reasons given for why clinicians in general did not perform urine drug testing included uneasiness with having to explain to patients why testing was needed, difficulty with accessing tests, inadequate knowledge to interpret test results, and suspecting a patient was a low-risk candidate for COT.20–23

While urine drug testing may be contentious, it only remains a supplement to the many other equally important elements that assist the clinician in risk stratifying patient when developing or modifying the pain management treatment plan:

  • Performing a focused history and physical examination
  • Reviewing any available pertinent past medical records
  • Reviewing the prescription drug monitoring program (PDMP)
  • Remaining vigilant for behavior issues (self-escalation, reports of lost or stolen prescriptions, frequent phone calls to the clinic, specific drug requests due to alleged intolerances or allergies, or use of >1 prescriber)

Urine drug testing allows the clinician to verify the patient’s self-report of prescribed or illicit drug use by objectively evaluating whether the patient is adhering to the treatment plan to justify ongoing COT versus the patient is disregarding the treatment plan to support tapering or stopping COT.24 Urine drug testing should be considered as a means of enhancing patient care because one cannot reliably predict aberrant drug-related behavior and because one cannot rely on patient self-reports of prescribed or illicit drug use.10,12,18,25–28 Noncompliance with taking an opioid as prescribed, however, is not uncommon. For example, in a retrospective analysis of 470 urine drug testing results from a pain clinic at an urban teaching hospital, Michna et al29 found noncompliance with COT occurred in 45% of the results. The noncompliant results consisted of illegal drugs (20.2%), additional prescription drugs (14.4%), absence of the prescribed opioid (10.2%), and evidence of specimen tampering (2.3%). In comparison, Turner et al30 retrospectively analyzed 5420 urine drug testing results from a large nonprofit health care system consisting of 25 ambulatory primary care clinics and found that noncompliance with COT occurred in 30.6%. The noncompliant results consisted of absence of the prescribed opioid (11.2%); presence of marijuana (11.2%), nonprescribed opioids (5.3%), illegal drugs (0.6%), or nonprescribed benzodiazepines; and evidence of specimen tampering (4.8%). The results that Quest Diagnostics (a major national clinical laboratory in the United States) discovered with a retrospective analysis of their own enormous pool of internal data consisting of 3.1 million urine drug testing results (from nonaddiction specialists and nondrug rehabilitation clinics during 2011–2015) suggest noncompliance may actually be more common than compliance.31 While obviously an industry-sponsored study, Quest Diagnostics’ authors determined that 54% of specimens revealed inconsistent results and 46% revealed consistent results. Furthermore, the noncompliant results consisted of prescribed opioid plus nonprescribed illicit or controlled substances (45%), nonprescribed illicit or controlled substances only (23%), and absence of the prescribed opioid (32%). Fortunately, over the same years, the authors noted a decline in overall inconsistent results from 63% in 2011 to 54% in 2015. They surmised the reasons for the decline were multifactorial: clinicians using their state’s PDMP, federal and state governmental agencies mandating safe opioid practices, various primary care and specialty medical societies sponsoring continuing medical education on rational opioid prescribing, patients becoming more educated about the hazards of COT, and law enforcement becoming more involved. Anticipating that they may be randomly urine drug tested may force some patients to make positive life changes from the start, whereas those who have aberrant results may make those same positive changes after agreeing to seek professional help to address their substance abuse disorder.32

Surprisingly, the explosion in the number of tests ordered has raised concerns that patients are being urine drug tested more for financial gain and less for medical necessity, with some clinical practices generating substantial portions of their revenue simply from these tests.11 For example, Medicare data revealed that the number of point-of-care (POC) immunoassay screens (IASs) reimbursed increased from 101 in 2000 to >3.2 million in 2009.33 Consider that the while the cost for urine drug testing can range from $5 to $10, the drug testing company can charge insurance companies anywhere from $250 to $1400.16 Ultimately, either the insurance company or the patient (by virtue of having inadequate insurance or lack of insurance) bears the cost. In another example, drug testing laboratories that analyze the urine specimens increased their sales from $800 million in 1990 to $2 billion in 2013.10,33,34 Hefty multimillion dollar settlements have been paid by 3 of the largest drug testing laboratories to resolve kickback claims and false billing charges to federal and private payers: Ameritox paid $16.4 million in 2010, Calloway Laboratories paid $20 million in 2012, and Millennium Health paid $256 million in 2015.34,35 Since the indications and frequency of testing may differ among the various insurance products, clinicians need to be aware of this. Medicare’s Local Coverage Determination for Controlled Substance Monitoring and Drugs of Abuse Testing breaks down the indications and frequency of testing even further in terms of the patient population being tested: (1) symptomatic patients, multiple drug ingestion, and/or patients with unreliable history; (2) diagnosis and treatment for substance abuse or dependence; and (3) treatment for patients on COT.36 Since Medicare Local Coverage Determination’s may vary regionally, prescribers are advised to check the one that applies to their geographical area of practice.


Bodily specimens that can be tested include urine, blood, hair, sweat, or saliva. For purposes of comparison, the advantages and disadvantages of testing the various bodily specimens are summarized in Table 1. Currently, though, urine remains the ideal specimen to test for clinical purposes because it has the most published scientific data.

Table 1.:
Bodily Specimens That Can Be Tested

Comprehensive urine drug testing involves 2 steps: an IAS followed by a confirmatory urine drug test (UDT). An IAS is only a qualitative test that looks for which drug/drug classes are present versus absent.20,24 At a minimum, the majority of IASs look for amphetamine, cocaine, marijuana, PCP, and opiates (limited to codeine, morphine, and 6-monoacetyl-morphine to test for heroin use); this also happens to be the same drug classes analyzed by federal drug testing programs.44 However, maintaining such a limited IAS panel in the pain management setting is not recommended, and instead it should be customized to also include benzodiazepines, barbiturates, methamphetamine, semisynthetic opioids, methadone, and buprenorphine. Because the cost of testing is related to the number of substances analyzed, cost constraints will prohibit the identification of every possible drug or illicit substance. IASs suffer from added limitations that include:20,24,45,46 (1) cross-reactivity with other drugs and substances that can lead to higher false-positive results (Table 2); (2) the inability to distinguish a positive opiate result as being due to codeine versus morphine versus heroin versus any combination of the aforementioned; (3) the inconsistency or inability to detect semisynthetic opioids (hydrocodone, hydromorphone, oxycodone, oxymorphone, buprenorphine) and synthetic opioids (fentanyl, meperidine, methadone, and pentazocine); (4) higher thresholds of detection that can potentially cause one to falsely conclude that a substance is absent when it is truly present; and (5) the inability to accurately conclude whether the identification of both the parent drug and its active metabolite (eg, codeine → morphine, oxycodone → oxymorphone, hydrocodone → hydromorphone, etc) means the patient is compliant versus the identification of the “active metabolite” really represents surreptitious use of a nonprescribed opioid and the patient is noncompliant. However, there are a number of advantages for always including an IAS: (1) low cost; (2) identification of illicit substances; and (3) potential acquisition of results in minutes to hours to enable one to make more immediate treatment decisions.37,38,48,49 The most rapid turn-around time for results occurs when using a POC IAS within the office setting (as opposed to sending it to a laboratory for analysis), but test result reliability is highly dependent on having skilled office personnel who know how to analyze and interpret the specimen according to the test manufacturer’s strict instructions.24,37,38,48,49 Ultimately, clinicians must understand that all IASs are only helpful for making preliminary treatment decisions.

Table 2.:
Drugs that May Cause False-Positive Results on an Immunoassay Screen46 , 47

Deciding whether to use a POC IAS versus laboratory-based IAS may be influenced by cost, insurance coverage, how quickly one wants the results, and personal preference (eg, POC testing requires teaching someone in the office to run and analyze the test versus laboratory-based testing which uses formally trained skilled laboratory technicians). Clinicians should be aware, though, that insurance companies are unlikely to reimburse charges for both a POC IAS and laboratory-based IAS performed for the same clinic visit. This is definitely true for Medicare.36 Not only does this result in nonreimbursement for one of the tests but also it leaves the patient potentially liable for paying out-of-pocket for the test not reimbursed by the insurance company.

Metabolism of some of the more common opioids.47 , 51 IAS indicates immunoassay screen; UDT, urine drug test.

The second component of comprehensive urine drug testing includes confirmatory UDT, which involves laboratory-based testing utilizing the techniques of gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS). Essentially, chromatography separates the analytes in a specimen, and mass spectrometry unequivocally identifies the relevant analytes by their mass-to-charge ratio.38,50 Because of their advanced technology, both GC-MS and LC-MS offer a higher level of specificity, accuracy, and sensitivity than can be achieved with an IAS. Unlike an IAS which only provides qualitative results for opiates and inconsistent/unobtainable results for semisynthetic and synthetic opioids, a UDT can provide quantitative information about individually identified opiates, opioids, and their respective metabolites. This level of specificity is critical for the care of those patients being prescribed >1 opioid or for those patients on an opioid that happens to metabolize into an active metabolite (eg, codeine → morphine, oxycodone → oxymorphone, hydrocodone → hydromorphone, etc) (Figure). The ability of GC-MS and LC-MS to provide both a qualitative and quantitative answer about the parent drug and metabolite means equivocal IAS results can be potentially resolved, thereby decreasing the likelihood for false-positive results.24 The degree of detailed information provided by a UDT outweighs its limitations of being available only as a laboratory-based test that has a turn-around time of hours to days.24


While the thresholds for detection have been standardized in the federal and work setting, they have not been standardized for the pain management setting.50 Results from both an IAS and UDT are limited by their individual thresholds of detectability. However, the thresholds are higher in an IAS compared to a UDT: eg, the threshold for detection of morphine is 300 ng/mL for an IAS and 50 ng/mL for a UDT.9 A drug’s pharmacokinetics, pharmacodynamics, and pharmacogenetics and how the urine specimen is collected, handled, and analyzed all can affect the threshold of detection.52 How long an individual continues to excrete a drug or its metabolite at or above a test’s lowest threshold of detectability determines a drug’s window of detection (Table 3), and this is influenced by the drug’s pharmacokinetics, pharmacodynamics, and pharmacogenetics.20,48,53 Many of the window of detection tables published in the literature are calculated based on single-dose administrations of the drug.38 For some drugs, such as marijuana, heroin, and PCP, a greater frequency or chronicity of use can result in unexpectedly longer detection times.38

Table 3.:
Window of Detection38 , 47 , 51

When the drug is absent or the concentration falls below the threshold of detectability, the result is reported as negative, and when the concentration rises above the threshold of detectability, it is reported as positive.54 In addition to the threshold of detection, an IAS’s or UDT’s ability to accurately identify a drug, metabolite, or illicit substance depends on each test’s specificity and the concentration of the drug in the urine.38 All of these variables account for why there is no scientific correlation between drug concentration versus drug dose, frequency of drug use, and when the last dose was taken.55 Because thresholds of detectability may differ among laboratories, clinicians are strongly encouraged to contact their laboratory to ensure the lowest threshold of detectability is used to maximize true positive results and minimize false-negatives.45 However, the consequence of requesting the lowest threshold of detectability means there is a greater likelihood of picking up an impurity due to another opioid being manufactured using the same equipment. Therefore, caution must be exercised when interpreting test results.

Because urine drug testing can potentially result in false-positive or false-negative results, misinterpretation of the result can detrimentally affect the patient’s pain control if COT is unnecessarily discontinued and the patient is misdiagnosed as having a substance misuse/abuse disorder.9,11,49 Erroneous conclusions that lead to a clinician stopping a patient’s opioid is not only detrimental to the patient but also potentially precarious to the prescriber from a legal standpoint.56 A correct interpretation of the results requires clinicians understand that results can be affected by drug interference patterns, cross-reactivity, and drug metabolism. In addition to providing the results, some laboratories will provide clinicians with a detailed description of how to interpret the results. With or without this description, though, clinicians should always contact the laboratory when uncertain about the meaning of the results.

Clinicians must also understand that inherent limitations of both an IAS or UDT can also potentially lead to a misinterpretation of the results. One can broadly outline the test results as follows:

  1. Negative results
    • a. True-negative
    • b. False-negative
    • c. Pseudo-false-negative
    • d. Negative due to inherent limitations of a test
  2. Positive results
    • a. True-positive
    • b. False-positive
    • c. Pseudo-false-positive

The absence of a drug is considered a true-negative result.54 More specifically, the result is considered true because it is consistent with no drug being prescribed or based on the patient’s self-report. However, when a prescribed drug is undetected, determining why the drug is absent becomes especially vexing. Possible explanations include laboratory error due to mislabeling the specimen, mishandling of the specimen, or using faulty equipment; the patient did not consume the medication because he/she forgot to take it, is hoarding it, or is diverting it; or the result is really a false-negative or pseudo-false-negative.

When a drug whose concentration is anticipated to fall at or above the threshold of detection is undetected, this is considered a false-negative.54 This could be due to laboratory error, adulteration, or inherent limitations of a test.20,49,50

Rapid metabolization of an opioid, either due to polypharmacy or a patient’s genetic predisposition, can prevent identification of the opioid on testing.50,54 This defines a pseudo-false-negative because the test correctly failed to confirm the presence of the opioid even though the patient is taking it.

Negative results due to inherent limitations of a test may preclude detection of a drug or its metabolite. If a patient infrequently uses an opioid, the test may not identify the opioid or its metabolite if the level falls below the test’s threshold of detectability. The likelihood of this occurring may be greater with an IAS compared to a UDT because of the IAS’s relatively higher threshold of detectability. For example, if testing is performed >8 hours after taking a short-acting opioid, the concentration may not be detected.54 An IAS has additional limitations not found in a UDT. First, while an IAS reliably detects opiates (codeine and morphine), it inconsistently identifies the presence of semisynthetic opioids (buprenorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone) and synthetic opioids (fentanyl, meperidine, and methadone) due to variable cross-reactivity.44,54 Second, an IAS generally does not detect opioid metabolites from the cytochrome P450 enzyme system.44 Depending on the opioid, the parent compound could be gone within 6–24 hours of consumption, leaving the prevalence of the undetected metabolite as the only marker ranging from 2.2% to 53.1% of the time.44

Positive results can be classified as true-positives, false-positives, and pseudo-false-positives. Presence of a drug above the threshold of detectability defines a true-positive result.54 More specifically, the result is considered true because it is consistent with the drug being prescribed or the patient’s self-report. Beyond that, though, the urine concentration cannot provide specifics on the opioid pertaining to generic versus name brand, the dose consumed, or the timing of the consumption.20,38 Consequently, one would be challenged to determine if a patient has taken the drug at the prescribed dose and frequency versus the patient has taken just the right amount at the right time to illicit a positive result, while diverting the remaining amount. Unexpected true-positive results may also occur if cocaine is used during an otolaryngology procedure and testing is done within cocaine’s benzoylecgonine metabolite window of detectability.

When a drug that is truly absent is identified as present, this is considered a false-positive.54 Laboratory error (eg, performing the test incorrectly or analyzing the wrong patient’s specimen) or drug interference/cross-reactivity are possible explanations.50

A pseudo-false-positive result means the test correctly identifies the presence of a drug, but it is not due to the patient taking that specific drug.54 This can occur in the following settings. First, the metabolism of a parent opioid to a secondary opioid (eg, oxycodone → oxymorphone, hydrocodone → hydromorphone, morphine → hydromorphone, codeine → morphine, and heroin → morphine) can cause one to erroneously conclude the patient is taking an unprescribed opioid or illicit substance. (The Figure summarizes the metabolism of some of the more common opioids.)38,51 Heroin can be especially difficult to identify because it metabolizes within minutes to 6-monoacetyl-morphine, a unique intermediary metabolite that confirms heroin use before its final metabolism to morphine. Second, foods that contain poppy seeds can lead to an IAS result that is positive for opiates.57 Third, marijuana and the synthetic cannabinoids dronabinol (Marinol) and nabiximols (Sativex) all contain 11-nor-delta-9-tetrahydrocannabinol-9 (THC) and will positively identify the THC metabolite, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid.55 (Nabilone [Cesamet] will not be detected because it does not have THC.55) Last, impurities of the manufacturing process can lead to the identification of a small amount of codeine when morphine is the prescribed opioid or a small amount of hydrocodone when oxycodone is the prescribed opioid. Incorrect interpretations of these types of pseudo-false-positive results falsely suggest the patient has a substance abuse disorder.

To minimize the challenges that can occur with interpreting unexpected results after the fact, the clinician should document the patient’s responses to the following questions before requesting a urine specimen:

  • If you are prescribed an opioid, which one are you taking, what dose are you taking, how often are you taking it, and when did you last take it?
  • If you are taking any other prescribed, nonprescribed, or over-the-counter drug or any illicit substance, which one are you taking, what dose are you taking, how often are you taking it, and when did you last take it?
Table 4.:
What to Do When the Results Are Unexpected

Having the responses to the questions above in advance of receiving the test results should improve the probability of arriving at the correct conclusion. Determining what to do when the results are unexpected, including whether or not to discharge a patient from the practice, requires careful consideration (Table 4).


Because some patients intentionally try to subvert the tests, clinicians should always be aware that adulteration might be a possibility. Scientists at Quest Diagnostics discovered that out of 2.1 million test results, patients had adulterated 33,396 (1.5%) of them by diluting them (60%), adding an oxidant (21%), substituting an alternate specimen (12%), or adding some other adulterant (7%).58 A quick search of the internet describes the many different techniques or commercial products a patient can use to subvert urine drug testing. Ingesting large amounts of water or the addition of household products (bleach, vinegar, and detergent), over-the-counter medications (eye drops and sodium chloride), or commercially purchased agents can decrease the concentration of drug detected.44,59 To disguise the pale appearance of urine that occurs after oral dilution, ingesting niacin or vitamin B will recreate the yellow color.38 Products that can be easily purchased over the Internet include “cleansing” agents and additives, synthetic urine substitutes, pouches to store synthetic urine substitutes or unadulterated urine, heaters, and skin tone-colored prosthetic devices (Table 5).44,54,59–65 If they know there is a good chance they will be tested, unscrupulous patients will even empty their bladder and reverse catheterize themselves with somebody else’s urine.

Table 5.:
Products Used for Urine Adulteration or Substitution44 , 54 , 59–65
Table 6.:
Validity Testing

Since looking at the appearance of the urine specimen is inadequate for determining if it has been adulterated, various strategies can be implemented either before or at the time the patient submits a specimen.38,66 To obtain the most concentrated specimen, have the patient submit a morning specimen. To eliminate the chance of diluting the specimen, shut off the water supply to any sink that is in the bathroom, and color tint the water in the toilet bowl and tank. To prevent chemical adulteration, do not store any cleaning compounds or medications in the bathroom. To minimize the chance of urine substitution from another individual, do not allow anyone to accompany the patient into the bathroom. This does not, however, eliminate the chance that the patient is using a pouch that can be catheterized. To prevent this, the specimen collection has to be witnessed. This, however, is not commonly done within a pain management setting because of the human resource allocation of assigning a clinic employee to this role. Nevertheless, a witnessed specimen collection is recommended for patients in whom adulteration is suspected or in those being treated for addiction. To ensure the specimen has not been adulterated, clinicians should ask the laboratory to perform validity testing.20 Recommended measurements and their associated normative ranges in adults, where appropriate, are included in Table 6.


While all patients with CNMP deserve to have their pain treated, the use of opioids in this patient population is fraught with pitfalls unless one has a complete understanding of each patient’s risk profile. To confirm the veracity of a patient’s responses to questions about his/her controlled substance use or illicit substance use, the clinician should consider obtaining an IAS and UDT. Even though urine drug testing has been universally recommended in various guidelines, they are inconsistent in recommending which population should be tested and at what frequency beyond the initial and annual testing.10,19,70–81 Chou et al70 concluded the evidence was low quality for monitoring patients, irrespective of whether the patient was considered low risk or high risk. While the authors gave a “weak” recommendation for random testing in low-risk patients, they gave a “strong” recommendation for random testing in high-risk patients or those engaging in aberrant drug-related behaviors.

Similar to the absence of strong evidence-based guidelines that identify which patients with CNMP should be tested, there are no definitive guidelines that inform clinicians on the frequency of testing. Most guidelines recommend testing new patients, at a minimum, before the initiation of COT and annually.11 However, such low frequency testing clearly does not apply to all patients. Of course, when patients exhibit suspicious behavior (eg, reports of a lost or stolen prescription, self-escalation, obtaining scripts from >1 provider, or asking for a specific opioid), testing should be performed at the time of the visit.20,55,66 However, Katz et al28 found that drug testing only those who have behavioral issues missed 21% of those with no behavioral issues but whose urine revealed presence of an illicit substance or nonprescribed drug. Because behavioral monitoring alone and patient self-report of prescribed and nonprescribed drug use are insufficient, clinicians should consider a monitoring frequency based on risk stratifying a patient as a low-, moderate-, or high-risk patient.20,36,53,82 Regardless of risk, clinicians should perform baseline testing before starting COT or on inheriting a patient from another provider. Consider random testing 1–2 times every 12 months for low-risk patients; 1–2 times every 6 months for moderate-risk patients; and 1–3 times every 3 months for high-risk patients or when the daily prescribed opioid dose is >120 mg morphine equivalents per day. For a patient who is unable to provide a specimen because he/she recently urinated or because he/she has pressing time constraints, clinicians need not feel trapped by having to choose between filling the prescription as usual versus denying the refill. Other possible choices include: (1) giving the usual prescription later that day after the patient can return to provide a specimen, or (2) giving a time-limited prescription (eg, 1–3 days) with the caveat that a specimen be provided within that same time frame, after which a new prescription is given for the residual number of days.32

While there remains insufficient evidence that testing leads to improved clinical outcomes or deters against substance use, purported benefits include greater compliance when patients know they may be asked to submit a specimen and enhanced patient care when test results suggest a referral to an addiction specialist is needed.11,14,23,38,70,83 Given that the use of race, ethnicity, socioeconomic status, or gender characteristics have all proven to be inaccurate in determining who will have an abnormal urine drug testing result, the best recommendation is to have a uniform practice policy of combining random drug testing with other monitoring techniques to avoid stigmatizing patients.20,23,28,29,38,49,51


The overprescription of opioids for CNMP during the past decade has resulted in a public health care crisis due to the parallel increase in opioid use disorders, deaths from overdose, and subsequent harms to communities.23,84–86 In an attempt to stem the tide of the opioid epidemic, opioid guidelines created by numerous medical societies and policies created by state and federal regulatory bodies have recommended urine drug testing, even though the scientific evidence is not strong.45,71,80,86 Urine drug testing can provide an additional data point when assessing for risk, but unfortunately, few patients are actually tested.19 Random urine drug testing should be included as part of an adherence monitoring program because patient self-reports and behavioral observation are unreliable.49,87 Combining urine drug testing with reviewing the PMDP can provide objective data that help support the clinician’s decision to continue versus discontinue COT.

Like any other diagnostic test, urine drug testing has its limitations. This means one must be cautious in interpreting what a “positive” versus “negative” result means. However, when the meaning of the result is unclear, contact the laboratory to avoid making an erroneous assessment that could harm the patient. Having a urine drug testing policy as part of one’s risk management plan (1) enhances patient care by refining the treatment plan based on expected or unexpected results; (2) demonstrates to patients, law enforcement authorities, and regulatory authorities that patient and community safety are a top priority; and (3) may deter individuals with strictly opioid-seeking behaviors.20,32,36,55


Name: Gagan Mahajan, MD.

Contribution: This author wrote, edited, and prepared the manuscript.

Conflicts of Interest: G. Mahajan is an opioid REMS speaker for Miller Medical Communications.

This manuscript was handled by: Honorio T. Benzon, MD.


1. Olsen Y, Daumit GL, Ford DEOpioid prescriptions by U.S. primary care physicians from 1992 to 2001. J Pain. 2006;7:225–235.
2. Zerzan JT, Morden NE, Soumerai S, et al.Trends and geographic variation of opiate medication use in state Medicaid fee-for-service programs, 1996 to 2002. Med Care. 2006;44:1005–1010.
3. Aitken M, Kleinrock M, Lyle J, Nass DMedicines use and spending shifts: a review of the use of medicines in the U.S. in 2014. 2015. Available at: Accessed May 9, 2017.
4. Manchikanti L, Fellows B, Ailinani H, Pampati VTherapeutic use, abuse, and nonmedical use of opioids: a ten-year perspective. Pain Physician. 2010;13:401–435.
5. Schuchat A, Houry D, Guy GP JrNew data on opioid use and prescribing in the United States. JAMA. 2017;318:425–426.
6. Volkow ND, Collins FSThe role of science in addressing the opioid crisis. N Engl J Med. 2017;377:391–394.
7. The American Pain Society. American Academy of Pain Medicine. Clinical Guideline for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain: Evidence Review. 2009. Chicago, IL: The American Pain Society; Available at: Accessed June 11, 2016.
8. Chou R, Turner JA, Devine EB, et al.The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:276–286.
9. Christo PJ, Manchikanti L, Ruan X, et al.Urine drug testing in chronic pain. Pain Physician. 2011;14:123–143.
10. Knezevic NN, Khan OM, Beiranvand A, Candido KDRepeated quantitative urine toxicology analysis may improve chronic pain patient compliance with opioid therapy. Pain Physician. 2017;20:S135–S145.
11. Manchikanti L, Kaye AM, Knezevic NN, 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–S92.
12. Economu S, Parks B, Puckett MMultiple cause of death data. 2014. Available at: Accessed June 11, 2016.
13. Pomerleau AC, Nelson LS, Hoppe JA, Salzman M, Weiss PS, Perrone JThe impact of prescription drug monitoring programs and prescribing guidelines on emergency department opioid prescribing: a multi-center survey. Pain Med. 2017;18:889–897.
14. Kaye AD, Jones MR, Kaye AM, et al.Prescription opioid abuse in chronic pain: an updated review of opioid abuse predictors and strategies to curb opioid abuse (part 2). Pain Physician. 2017;20:S111–S133.
15. Rudd RA, Seth P, David F, Scholl LIncreases in drug and opioid-involved overdose deaths—United States, 2010–2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445–1452.
16. Pergolizzi J, Pappagallo M, Stauffer J, et alIntegrated Drug Compliance Study Group (IDCSG). The role of urine drug testing for patients on opioid therapy. Pain Pract. 2010;10:497–507.
17. Adams NJ, Plane MB, Fleming MF, Mundt MP, Saunders LA, Stauffacher EAOpioids and the treatment of chronic pain in a primary care sample. J Pain Symptom Manage. 2001;22:791–796.
18. Bhamb B, Brown D, Hariharan J, Anderson J, Balousek S, Fleming MFSurvey of select practice behaviors by primary care physicians on the use of opioids for chronic pain. Curr Med Res Opin. 2006;22:1859–1865.
19. Morasco BJ, Peters D, Krebs EE, Kovas AE, Hart K, Dobscha SKPredictors of urine drug testing for patients with chronic pain: results from a national cohort of U.S. veterans. Subst Abus. 2016;37:82–87.
20. Heit HA, Gourlay DLUrine drug testing in pain medicine. J Pain Symptom Manage. 2004;27:260–267.
21. Reisfield GM, Webb FJ, Bertholf RL, Sloan PA, Wilson GRFamily physicians’ proficiency in urine drug test interpretation. J Opioid Manag. 2007;3:333–337.
22. Tellioglu TThe use of urine drug testing to monitor patients receiving chronic opioid therapy for persistent pain conditions. Med Health R I. 2008;91:279–80, 282.
23. Ceasar R, Chang J, Zamora K, et al.Primary care providers’ experiences with urine toxicology tests to manage prescription opioid misuse and substance use among chronic noncancer pain patients in safety net health care settings. Subst Abus. 2016;37:154–160.
24. Webster LRThe Role of Urine Drug Testing in Chronic Pain Management: 2013 Update. 2013. New York, NY: McMahon Publishing; Available at: Accessed May 8, 2016.
25. Setnik B, Roland CL, Pixton GC, Sommerville KWPrescription opioid abuse and misuse: gap between primary-care investigator assessment and actual extent of these behaviors among patients with chronic pain. Postgrad Med. 2017;129:5–11.
26. Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland CLSocietal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain Med. 2011;12:657–667.
27. Kaye AD, Jones MR, Kaye AM, et al.Prescription opioid abuse in chronic pain: an updated review of opioid abuse predictors and strategies to curb opioid abuse: part 1. Pain Physician. 2017;20:S93–S109.
28. Katz NP, Sherburne S, Beach M, et al.Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth Analg. 2003;97:1097–1102.
29. Michna E, Jamison RN, Pham LD, et al.Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings. Clin J Pain. 2007;23:173–179.
30. Turner JA, Saunders K, Shortreed SM, et al.Chronic opioid therapy urine drug testing in primary care: prevalence and predictors of aberrant results. J Gen Intern Med. 2014;29:1663–1671.
31. McClure L, Niles J, Kaufman MPrescription drug misuse in America: diagnostic insights in the continuing drug epidemic battle. Quest Diagnostics Health Trends Prescription Drug Monitoring Report. 2016:1–23. Available at: Accessed June 23, 2017.
32. Heit HA, Gourlay DLUsing urine drug testing to support healthy boundaries in clinical care. J Opioid Manag. 2015;11:7–12.
33. Kaye AD, Marshall ZJ, Lambert SM, et al.Ethical perspectives on urine drug screening for pain physicians. Pain Physician. 2014;17:E559–E564.
34. Meier BIncrease in urine testing raises ethical questions. 2013. Available at: Accessed June 19, 2017.
35. U.S. Attorney’s Office. Millennium Laboratories to pay $256 million to resolve false billing and kickback claims. 2015. Available at: Accessed May 19, 2017.
36. Centers for Medicare & Medicaid Services. Local Coverage Determination (LCD): controlled substance monitoring and drugs of abuse testing (L36668). 2016. Available at:*1&Cntrctr=360&name=Noridian+Healthcare+Solutions%2c+LLC+(Noridian+Healthcare+Solutions%2c+LLC+(01111%2c+A+and+B+MAC%2c+J+-+E))&LCntrctr=360*1&DocType=Future&bc=AAAAAAIAAAAAAA%3d%3d&. Accessed June 28, 2016.
37. Substance Abuse and Mental Health Services Administration. Clinical Drug Testing in Primary Care. 2012. Rockville, MD: US Department of Health and Human Services; Available at: Accessed June 30, 2016.
38. Hammett-Stabler C, Webster LA Clinical Guide to Urine Drug Testing: Augmenting Pain Management and Enhancing Patient Care. 2008. Stamford, CT: PharmaCom Group, Inc; Available at: Accessed April 7, 2017.
39. Caplan YH, Goldberger BAAlternative specimens for workplace drug testing. J Anal Toxicol. 2001;25:396–399.
40. Yacoubian GS Jr, Wish ED, Perez DMA comparison of saliva testing to urinalysis in an arrestee population. J. Psychoactive Drugs. 2001;33:289–294.
41. Cone EJOral fluid testing: new technology enables drug testing without embarrassment. J Calif Dent Assoc. 2006;34:311–315.
42. Cone EJ, Huestis MAInterpretation of oral fluid tests for drugs of abuse. Ann N Y Acad Sci. 2007;1098:51–103.
43. Nichols JH, Christenson RH, Clarke W, et alNational Academy of Clinical Biochemistry. Executive summary. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guideline: evidence-based practice for point-of-care testing. Clin Chim Acta. 2007;379:14–28.
44. DePriest AZ, Black DL, Robert TAImmunoassay in healthcare testing applications. J Opioid Manag. 2015;11:13–25.
45. Bauer SR, Hitchner L, Harrison H, Gerstenberger J, Steiger SPredictors of higher-risk chronic opioid prescriptions in an academic primary care setting. Subst Abus. 2016;37:110–117.
46. Standridge JB, Adams SM, Zotos APUrine drug screening: a valuable office procedure. Am Fam Physician. 2010;81:635–640.
47. Mahajan GBenzon H, Raja SN, Fishman S, Liu S, Cohen SPUrine drug testing in pain medicine. Essentials of Pain Medicine. 2017:4th ed. Philadelphia, PA: Elsevier405–418.
    48. Manchikanti L, Atluri S, Trescot AM, Giordano JMonitoring opioid adherence in chronic pain patients: tools, techniques, and utility. Pain Physician. 2008;11:S155–S180.
    49. McCarberg BHA critical assessment of opioid treatment adherence using urine drug testing in chronic pain management. Postgrad Med. 2011;123:124–131.
    50. McMillin GA, Slawson MH, Marin SJ, Johnson-Davis KLDemystifying analytical approaches for urine drug testing to evaluate medication adherence in chronic pain management. J Pain Palliat Care Pharmacother. 2013;27:322–339.
    51. Carlozzi A, Fornari F, Siwicki D, et alUrine Drug Monitoring: Opioids. 2009. New York, NY: McMahon Publishing; Available at: Accessed April 12, 2016.
    52. Nafziger AN, Bertino JS JrUtility and application of urine drug testing in chronic pain management with opioids. Clin J Pain. 2009;25:73–79.
    53. Washington State Agency Medical Directors’ Group. Interagency Guideline on Prescribing Opioids for Pain. 2015. 3rd ed. Olympia, WA: State of Washington Department of Health; Available at: Accessed July 17, 2016.
    54. Reisfield GM, Salazar E, Bertholf RLRational use and interpretation of urine drug testing in chronic opioid therapy. Ann Clin Lab Sci. 2007;37:301–314.
    55. Gourlay D, Heit HUrine Drug Testing in Clinical Practice: Dispelling the Myths and Designing the Strategies. 2006. Stamford, CT: PharmaCom Group, Inc; Available at: drug testing in clinical practice.pdf. Accessed June 16, 2016.
    56. Reisfield GM, Bertholf R, Barkin RL, Webb F, Wilson GUrine drug test interpretation: what do physicians know? J Opioid Manag. 2007;3:80–86.
    57. Thevis M, Opfermann G, Schänzer WUrinary concentrations of morphine and codeine after consumption of poppy seeds. J Anal Toxicol. 2003;27:53–56.
    58. Blatt A, Chen Z, McClure L, Niles J, Kaufman MPrescription drug misuse in America: diagnostic insights in the continuing drug epidemic battle. Quest Diagnostics Health Trends Prescription Drug Monitoring Report. 2015:1–16. Available at: Accessed June 9, 2016.
    59. Jaffee WB, Trucco E, Levy S, Weiss RDIs this urine really negative? A systematic review of tampering methods in urine drug screening and testing. J Subst Abuse Treat. 2007;33:33–42.
    60. Pesce A, West C, Egan City K, Strickland JInterpretation of urine drug testing in pain patients. Pain Med. 2012;13:868–885.
    61. Substance Abuse and Mental Health Services Administration. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs. 2010. Rockville, MD: US Department of Health and Human Services; Available at: Accessed April 12, 2016.
    62. Always Test Clean. Available at: Accessed May 16, 2016.
    63. Detoxify LLC. Available at: Accessed May 16, 2016.
    64. Safe Solution. Available at: Accessed May 15, 2016.
    65. Detox for Less. Available at: Accessed May 16, 2016.
    66. Gourlay D, Heit H, Caplan YUrine Drug Testing in Clinical Practice: The Art and Science of Patient Care. 2015. Stamford, CT: PharmaCom Group, Inc; Available at: Accessed June 16, 2016.
    67. Quest Diagnostics Test Center. Random urine creatinine. Available at: Accessed June 9, 2016.
      68. Bush DMThe U.S. Mandatory Guidelines for Federal Workplace Drug Testing Programs: current status and future considerations. Forensic Sci Int. 2008;174:111–119.
      69. MedlinePlus: U.S. National Library of Medicine. Urine specific gravity test. Available at: Accessed June 9, 2016.
        70. Chou R, Fanciullo GJ, Fine PG, et alAmerican Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10:113–130.
        71. Fishman SResponsible Opioid Prescribing: A Clinician’s Guide. Revised and Expanded. 2014.2nd ed. Washington, DC: Waterford Life Sciences.
        72. Turner JA, Saunders K, Shortreed SM, et al.Chronic opioid therapy risk reduction initiative: impact on urine drug testing rates and results. J Gen Intern Med. 2014;29:305–311.
        73. Berland D, Rodgers PRational use of opioids for management of chronic nonterminal pain. Am Fam Physician. 2012;86:252–258.
        74. Popish SJ, Wells DL, Kimura H, Yee M, Christopher MLPain Management Opioid Safety Educational Guide. 2014. Washington, DC: US Department of Veterans Affairs; Available at: Accessed June 11, 2016.
        75. Hooten WM, Timming R, Belgrade M, et alAssessment and Management of Chronic Pain. 2013. 6th ed. Bloomington, MN: Institute for Clinical Systems Improvement; Available at: Accessed June 11, 2016.
        76. Utah Department of Health. Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain. Salt Lake City, UT. 2009. Available at: Accessed June 11, 2016.
        77. American College of Occupational and Environmental Medicine. ACOEM guidelines for chronic use of opioids. Elk Grove Village, IL. 2011. Available at: Pain Opioid.pdf. Accessed June 11, 2016.
        78. Manchikanti L, Abdi S, Atluri S, et alAmerican Society of Interventional Pain Physicians. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I–evidence assessment. Pain Physician. 2012;15:S1–S65.
        79. National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. National Opioid Use Guideline Group (NOUGG); 2010. Available at: Accessed June 11, 2016.
        80. Nuckols TK, Anderson L, Popescu I, et al.Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. 2014;160:38–47.
        81. Medical Board of California. Guidelines for Prescribing Controlled Substances for Pain. Sacramento, CA. 2014. Available at: Accessed June 16, 2016.
        82. Webster LR, Webster RMPredicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Med. 2005;6:432–442.
        83. Starrels JL, Becker WC, Alford DP, Kapoor A, Williams AR, Turner BJSystematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med. 2010;152:712–720.
        84. Gilson AM, Ryan KM, Joranson DE, Dahl JLA reassessment of trends in the medical use and abuse of opioid analgesics and implications for diversion control: 1997–2002. J Pain Symptom Manage. 2004;28:176–188.
        85. Rudd RA, Aleshire N, Zibbell JE, Gladden RMIncreases in drug and opioid overdose deaths—United States, 2000–2014. MMWR Morb Mortal Wkly Rep. 2016;64:1378–1382.
        86. Dowell D, Haegerich TM, Chou RCDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65:1–49.
        87. Chen WJ, Fang CC, Shyu RS, Lin KCUnderreporting of illicit drug use by patients at emergency departments as revealed by two-tiered urinalysis. Addict Behav. 2006;31:2304–2308.
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