Evidence-Based Reviews

Urine drug tests: How to make the most of them

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Interference from medications or diets. One example of a positive opioid screening result due to interference from diet is the consumption of foods that contain poppy seeds. Because of this potential interference, the cutoff value for a positive opioid immunoassay in workplace drug testing was increased from 300 to 2,000 ug/L.24 Educating patients regarding medication and lifestyle choices can help them avoid any interference with drug monitoring. Confirmatory tests can be ordered at the clinician’s discretion. The same principle applies to medication choice when prescribing. For example, a patient taking bupropion may experience a false positive result on a UDS for amphetamines, and a different antidepressant might be a better choice (Box 1).

Box 1

CASE: When medications interfere with drug monitoring

A patient with methamphetamine use disorder asked his psychiatrist for a letter to his probation officer because his recent urine drug screening (UDS) was positive for amphetamine. At a previous visit, the patient had been started on bupropion for depression and methamphetamine use disorder. After his most recent positive UDS, the patient stopped taking bupropion because he was aware that bupropion could cause a false-positive result on amphetamine screening. However, the psychiatrist could not confirm the results of the UDS, because he did not have the original sample for confirmatory testing. In this case, starting the patient on bupropion may not have been the best option without contacting the patient’s probation officer to discuss a good strategy for distinguishing true vs false-positive UDS results.

Urine sample tampering. Consider the possibility that urine samples could be substituted, especially when there are signs or indications of tampering, such as a positive pregnancy test for a male patient, or the presence of multiple prescription medications not prescribed to the patient. If there is high suspicion of urine sample tampering, consider observed urine sample collection.

When to order confirmatory tests for unexpected positive results.

Order a confirmatory test if a patient adamantly denies taking the substance(s) for which he/she has screened positive, and there’s no other explanation for the positive result. Continue the patient’s current treatment if the confirmatory test is negative. However, if the confirmatory test is positive, then modify the treatment plan (Algorithm).

Ordering UDTs, interpreting results, and implementing management strategies

Special circumstances.

A positive opioid screen in a patient who has been prescribed a synthetic or semisynthetic opioid indicates the patient is likely using opioids other than the one he/she has been prescribed. Similarly, clonazepam is expected to be negative in a benzodiazepine immunoassay. If such testing is positive, consider the possibility that the patient is taking other benzodiazepines, such as diazepam. The results of UDTs can also be complicated by common metabolites in the same class of drugs. For example, the presence of hydromorphone for patients taking hydrocodone does not necessarily indicate the use of hydromorphone, because hydromorphone is a metabolite of hydrocodone (Figure 215).

Unexpected negative results

Prescribed medications exist in low concentration that are below the UDS detection threshold. This unexpected UDS result could occur if patients:

  • take their medications less often than prescribed (because of financial difficulties or the patient feels better and does not think he/she needs it, etc.)
  • hydrate too much (intentionally or unintentionally), are pregnant, or are fast metabolizers (Box 2)
  • take other medications that increase the metabolism of the prescribed medication.

Box 2

CASE: An ultra-rapid metabolizer

A patient with opioid use disorder kept requesting a higher dose of methadone due to poorly controlled cravings. Even after he was observed taking methadone by the clinic staff, he was negative for methadone in immunoassay screening, and had a very low level of methadone based on liquid chromatography/mass spectrometry. Pharmacogenetic testing revealed that the patient was a cytochrome P450 2B6 ultra-rapid metabolizer; 2B6 is a primary metabolic enzyme for methadone. He also had a high concentration of 2-ethylidene- 1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), the primary metabolite of methadone, which was consistent with increased methadone metabolism.

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