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Opioid Prescribing and Monitoring - (Second Edition)
Primary Care Models for Pain Management

Assessment and Monitoring of Pain: Urine Drug Screening

It can take years to develop trusting relationships with patients, yet only seconds to destroy those relationships with false accusations. How to deftly handle abnormal urine drug tests (UDTs), therefore, is a critical skill when working in pain management.

Four general principles are important when ordering and interpreting results from UDTs:

  • Stratify patient risk and determine the frequency of testing required (eg, monthly, quarterly, yearly)
  • Seek definitive results to guide any decisions that will alter treatment, especially when it involves an unexpected result that cannot be reconciled
  • Plan in advance how abnormal results will be handled, and stick to your plan
  • When aberrant behavior is identified, do not ignore it; address it immediately, and document the medical record accordingly

Unfortunately, sending all UDTs for confirmation testing to obtain definitive results may result in steep penalties from Medicare and Medicaid for unnecessary or fraudulent lab orders.1 Spurring the recent scrutiny is the high cost of UDTs —10 to 20 times that of immunoassay tests. Litigation and hefty fines have been used in egregious cases of overuse. Reimbursement rates also have been reduced. Therefore, sending every test for confirmation is not standard of care, and ordering the right initial test requires forethought and knowledge of drug-specific tests.

There are two general types of UDTs routinely used in clinical practice: immunoassay testing and confirmation testing. Understanding their unique features and limitations is critical.

Immunoassay Testing

Immunoassay is often referred to as “in-office,” “point-of-care (POCT),” or “dipstick” testing. The test’s results are typically fast, inexpensive, and sensitive, but its lack of specificity can result in false positives. Extensive lists of common false positives are available and should be readily accessible when interpreting unexpected results. Apps and algorithms are also available to guide practitioners through this process. A UDT positive for cocaine is almost never a false positive because it specifically tests for benzoylecgonine, a metabolite unique to cocaine. Amphetamines, however, have a very high false positive rate, with numerous structurally similar prescription drugs able to trigger a positive UDT. Benzodiazepines and cannabinoid tests vary significantly based on the lab and the specificity of the assay used. However, in general, they, too, have a documented potential for false positives.

A standard opiate immunoassay screen does not detect all opioids equally. It is designed to detect morphine, as well as drugs metabolized to morphine, including opium (concentrated morphine), heroin (metabolized to morphine and 6-Monoacetylmorphine), and codeine (metabolized to morphine by CYP2D6). The screen also will detect other structurally similar opioids at higher concentrations, by default, but may result in false positives or negatives. While labs vary in their detection thresholds for hydrocodone and other synthetic opioids compared to morphine, a substantial dose of oxycodone is required to trigger a positive result on an opiate screen (Table 1). Many labs overcome this issue by including a separate oxycodone screen (100 ng/mL) to ensure that it is detectable at low doses.

Table 1. Standard Opiate Immunoassay Detection (300 ng/mL)

An opiate screen is not designed to detect opioids from different pharmacologic classes, such as fentanyl or methadone, or even most synthetic dehydroxylatedphenanthrenes with unique chemical structures, such as levorphanol or buprenorphine. Separate specialty immunoassay tests for many of these are available. While some labs offer comprehensive immunoassay tests that include every specialty screen, many do not. Practitioners must be familiar with available tests, and make informed choices. Of note, most labs keep urine samples for a limited period of time—some only 7 days—so if test results are unexpected, practitioners should determine whether the correct test has been requested for the prescribed medications and, if necessary, reorder in a timely manner.

Confirmation Testing

The second type of UDT is confirmation testing, which has both high sensitivity and high specificity, and is usually performed with either gas or liquid chromatography-mass spectrometry. Confirmation testing takes longer than immunoassay testing, and is more expensive, but its accuracy provides definitive results. Unlike immunoassays that provide only positive or negative qualitative results, confirmatory tests specify which drugs were present, along with metabolites and their respective quantitative concentrations. The threshold required for detection is substantially less, which ensures that the test will more likely capture the substances, if present. Correct interpretation of a confirmation test requires an understanding of the metabolites in commonly prescribed medications. Otherwise, practitioners could misinterpret the results to indicate that a patient is taking medications that are not prescribed (Table 2, page 52).

In 2016, the Centers for Medicare and Medicaid Services (CMS) replaced previous drug testing codes with dedicated Healthcare Common Procedure Coding System (HCPCS) “G” codes. The codes differentiate between presumptive testing (to ask whether a drug is present) and definitive testing (to provide a positive identification of the substance in question). Presumptive codes are eligible for reimbursement when testing is performed in an office, laboratory, or facility setting.

The definitive tests must be more sensitive and more specific than the initial screens. Definitive tests are performed in a laboratory or by a provider with a Certificate of Registration, Compliance of Accreditation, Medical Test Site Categorized License, or Accredited License. The tests are able to quantify the amount of drugs or metabolites present in the urine samples. Definitive tests can be used to confirm the presence of specific drugs identified by screening tests, and can identify drugs that cannot be isolated by currently available presumptive testing. Results are reported as specific levels of substances detected in the urine samples.

Occasionally, assistance is required in interpreting unexpected UDT results, and discussing them with another provider, clinical pharmacist, or laboratory toxicologist may be helpful. Result 1 in Table 2, for example, could lead providers to believe a patient is on multiple benzodiazepines and opioids, but this result should be interpreted as a patient taking diazepam (oxazepam and temazepam are metabolites) and hydrocodone (hydromorphone is a minor metabolite).

Table 2. Sample UDT Results From Confirmation Testing

Result 2 indicates a patient taking fentanyl (norfentanyl is the major metabolite) and lorazepam, as well as using marijuana. With most immunoassay tests, lorazepam and clonazepam won’t trigger a positive UDT. They require either a specific immunoassay or confirmation testing. The presence of cannabinoids in a confirmation test is definitive, so it was unquestionably in the patient’s system, in this example. A patient’s history and previous response to this test result, as well as clinic policy and state law, may then influence the decision whether or not to continue treatment.

Result 3 indicates that the patient was taking both oxymorphone and morphine, as they have no common metabolites. The bupropion result likely means that an initial positive test for amphetamines proved, upon confirmation, to be a false positive result. Research suggests bupropion is present in roughly 40% of amphetamine false positives.2

Confirmation testing should provide clarity regarding true UDT results and prepare the provider to exercise individual clinical judgment over unexpected results. At this point, the results are considered definitive and appropriate for guiding treatment decisions, and will not damage provider-patient relationships without cause.

The presence of nonprescribed controlled medications or illicit substances is considered aberrant behavior; it increases the risks of continuing treatment and may indicate misuse, abuse, or diversion. Inappropriate results require action by providers. Research in this area shows that nearly half of patients may demonstrate aberrant behavior with abnormal UDT results, and half of those will accept education and change their behavior. The rest will require tapering and discontinuation of medications and potential referral to a substance abuse treatment program.3 Aberrant behaviors increase risks, and the frequency of random UDTs, prescription-drug monitoring program queries, and follow-up visits should reflect these risks. Failure to act on definitive UDT results may leave providers open to legal or regulatory actions.

Difficult Discussions

While many practitioners prefer to perform confirmation testing prior to discussing results with the patient, a brief conversation after the initial results may alleviate the need for confirmation testing. Talking with the patient at this point may provide additional information, or, at the very least, an engaging story (Table 3, page 54).

In some cases, confirmation testing will not be necessary because the patient will be honest about the cause of the unexpected result. When the patient has no explanation, or his or her rationale raises red flags, confirmation testing should be ordered. A patient’s response to abnormal UDT results often provides insight into his or her attitudes toward compliance that can be impossible to discern under normal circumstances. Confrontation with patients at this stage is counterproductive and should be avoided. Nevertheless, this is an opportunity to reinforce policy with patients and remind them of potential consequences if confirmation testing confirms the presence of nonprescribed medications or illicit substances. Remember, it is critical to make decisions based upon definitive results and, unless the cause of the unexpected UDT result has been openly discussed, confirmation testing will provide certainty.

Table 3. Difficult Patient Conversations


The risks of misuse and abuse increase when patients exhibit aberrant behaviors. To mitigate these risks, clinicians can increase the frequency of random UDTs, pill counts, and follow-up visits.


More on this topic: Clinical Drug Monitoring online resource guide.

Last updated on: April 29, 2019
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