Charlotte Van Hale, MD Assistant Professor Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia
Rachel Gluck, MD PGY-4 General Psychiatry Resident Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia
Yi-lang Tang, MD, PhD Associate Professor Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia Addiction Psychiatrist Substance Abuse Treatment Program Atlanta Veterans Health Care System Decatur, Georgia
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Acknowledgments The authors thank Jennifer Casarella, MD, and Karen Hochman, MD, of Atlanta VA Medical Center, and the Department of Psychiatry and Behavioral Sciences, Emory University, for their comments on this article.
As part of the initial assessment, it is recommended to order CMP, UDS, and urine general toxicology.14 If indicated, specific laboratory tests such as specific opioid and alcohol metabolites screens can be ordered. After starting buprenorphine, the frequency of monitoring urine laboratory tests—including UDS, general drug toxicology, buprenorphine/norbuprenorphine/naloxone/creatinine, and alcohol and its metabolites—depends on a variety of factors, including a patient’s treatment response and stability as well as availability and cost of the tests. Ultimately, the frequency of laboratory monitoring should be determined on a patient-by-patient basis and clinicians should use their judgment.
The American Society of Addiction Medicine suggests testing more frequently earlier in the course of treatment (eg, weekly or biweekly), then spacing it out over time (eg, monthly or quarterly) as the patient’s recovery progresses.14,15 To conserve resources and reduce spending, some clinicians and guidelines recommend random monitoring as opposed to monitoring at every follow-up visit (eg, once out of every 3 to 5 visits, on average), which allows for longer intervals between testing while ensuring consistency with medication and abstinence from illicit substances.15,16 We suggest screening every 2 weeks for the first month, then spacing out to monthly and quarterly as patients demonstrate stability, with random screening as indicated. Monitoring of liver function should be done at least once annually.
4. How should urine buprenorphine and other results be interpreted?
There are several issues to consider when interpreting laboratory results. The clinician needs to know what to expect in the sample, and what approximate levels should be detected. To check treatment adherence, laboratory data should include stable urine buprenorphine and norbuprenorphine levels and negative urine screening for other illicit substances.14,15 While urine buprenorphine and norbuprenorphine levels have great interindividual variability due to genetic differences in hepatic metabolism, unusually high levels of buprenorphine (≥700 ng/mL) without norbuprenorphine suggests “urine spiking,” where patients put buprenorphine directly into their urine sample.20,21 Abnormally low or undetectable levels raise concern for medication nonadherence or diversion.
Though urine buprenorphine levels do not reliably correlate with dose, because there is typically not much intraindividual variability, patients should have relatively stable levels on each screen once a maintenance dose has been established.22 Furthermore, the buprenorphine-to-norbuprenorphine ratio (ie, “the metabolic ratio”) typically ranges from 1:2 to 1:4 across all individuals,20,21,23 regardless of dose or metabolic rate. Urine naloxone levels, which typically are included in commercial urine buprenorphine laboratory panels, also may aid in identifying tampered urine specimens when buprenorphine-to-norbuprenorphine ratios are abnormal or inconsistent with an individual’s prior ratio. Naloxone is typically (but not always) poorly absorbed and minimally detected in urine specimens.20 A high level of naloxone coupled with unusually high buprenorphine levels, particularly in the absence of norbuprenorphine in the urine, may indicate urine spiking.20,21,23
Urine creatinine is used to establish the reliability of the specimen. When urine creatinine concentration is <20 mg/dL, the concentration of most substances typically falls to subthreshold levels of detection.24 If a UDS is negative and the urine has a creatinine concentration <20 mg/dL, the patient should provide a new sample, because the urine was likely too diluted to detect any substances.
