In patients prescribed opioids for acute postoperative pain, chronic non‑cancer pain, cancer‑related pain, or opioid use disorder treatment, what is the recommended frequency of urine drug screening (UDS), which substances should be included in the comprehensive panel, and how should discordant or positive results for non‑prescribed drugs be managed?

Urine Drug Screening in Patients on Opioids

Perform baseline urine drug testing before initiating opioid therapy in all patients, then conduct annual screening for low-risk patients, with increased frequency (quarterly or more) for those with risk factors such as substance use history, psychiatric conditions, or concurrent benzodiazepine use. 1

Baseline Testing Requirements

• Obtain urine drug testing before starting any opioid therapy for chronic pain to establish reliability of the patient's substance use history and detect undisclosed substance use 1
• Apply this baseline testing universally to all patients ("we do this for everyone") to prevent bias and reduce stigmatization 1
• Use this initial test to identify concurrent use of benzodiazepines, illicit drugs (marijuana, cocaine, methamphetamine), and non-prescribed opioids that increase overdose risk 1

Ongoing Monitoring Frequency

For low-risk patients:

• Test at least annually once stable on chronic opioid therapy 1, 2
• Low-risk is defined as no personal/family history of substance use disorder, no psychiatric conditions, no aberrant drug-related behaviors, and no concurrent benzodiazepines 2

For moderate-risk patients:

• Test two or more times per year 3

For high-risk patients:

• Test three or more times per year (quarterly or more frequently) 1, 3
• High-risk characteristics include personal or family history of substance use disorder, concurrent psychiatric conditions, history of aberrant behaviors, concurrent benzodiazepine prescriptions, or receiving ≥90 morphine milligram equivalents daily 1, 2

For postoperative acute pain:

• Routine screening is not indicated for short-term postoperative opioid use (≤7 days) 1
• However, evaluate pain status at follow-up appointments and assess for continued opioid needs, as most patients should not require opioids beyond the immediate postoperative period 1

Testing Methodology and Panel Selection

Initial screening approach:

• Start with immunoassay panels for commonly prescribed opioids and illicit drugs (marijuana, cocaine, amphetamines, benzodiazepines) 1, 4
• Standard "opiates" immunoassays detect morphine and codeine but do NOT detect synthetic opioids like fentanyl, methadone, oxycodone, hydrocodone, or tramadol 1, 4
• For patients prescribed these synthetic opioids, order specific testing or proceed directly to confirmatory testing 1

Confirmatory testing indications:

• Order gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry (LC/MS) when immunoassay results are unexpected or discordant with clinical presentation 1
• Use confirmatory testing to differentiate specific opioids and metabolites, as immunoassays can produce false positives from pseudoephedrine, trazodone, and other medications 1, 2
• Restrict confirmatory testing to situations where results will actually affect patient management to control costs 1, 4

Comprehensive panel should include:

• Prescribed opioid(s) and their metabolites 1
• Benzodiazepines (critical due to overdose risk when combined with opioids) 1
• Illicit drugs: marijuana, cocaine, methamphetamine 1
• Non-prescribed opioids and heroin 1

Management of Discordant or Positive Results

Initial response to unexpected results:

• Discuss results with the patient in a non-judgmental manner BEFORE ordering confirmatory testing 1, 5
• Ask about over-the-counter medications, supplements, and obtain complete medication history, as many substances cause false positives 2, 5
• Consider alternative explanations: timing of medication use, cross-reactivity, specimen dilution, or laboratory error 5

For confirmed non-prescribed drug use:

• Check the Prescription Drug Monitoring Program (PDMP) to identify concurrent prescriptions from other providers 1, 5
• Assess for substance use disorder using validated tools and clinical interview 1, 5
• Increase monitoring frequency and schedule more frequent follow-up visits 5
• Consider implementing or revising the pain treatment agreement 5

For confirmed illicit drug use:

• Evaluate whether the patient meets criteria for substance use disorder 1
• Offer or arrange evidence-based treatment, typically medication-assisted treatment with buprenorphine or methadone combined with behavioral therapies 1
• Consider referral to addiction specialist while maintaining pain management 5
• Continue more frequent UDS monitoring (monthly or more) 5

For absent prescribed opioids:

• Consider whether the patient is diverting medications (selling or sharing) 1
• Evaluate for inadequate pain control leading to non-adherence 5
• Assess whether the patient can safely discontinue opioids without withdrawal 1

Critical Implementation Principles

Never dismiss patients from care based on UDS results alone - this constitutes patient abandonment, eliminates opportunities for lifesaving interventions, and adversely affects patient safety 1, 4

Pre-test communication:

• Explain to patients before ordering UDS that testing is intended to improve their safety, not as punishment 1
• Discuss expected results (presence of prescribed medication, absence of illicit drugs) 1
• Ask if there might be unexpected results to avoid unnecessary confirmatory testing 1

Standardized protocols:

• Apply UDS policies uniformly to all patients in the same risk category to prevent bias 1, 4
• Consider "collect frequently, test monthly" approach: collect specimens at every visit but send for testing on a predetermined schedule to destigmatize testing while maintaining monitoring effectiveness 4
• Use random rather than scheduled testing when additional monitoring is needed, as predictable testing increases tampering opportunities 1

Documentation requirements:

• Document comprehensive assessment, discussion with patient about results, and clinical decision-making in the medical record 5
• Record the rationale for testing frequency chosen based on risk stratification 5

Special Population Considerations

Cancer-related pain:

• Baseline UDS before initiating opioids is recommended, though evidence specific to cancer populations is limited 1, 6
• Frequency of ongoing monitoring in cancer patients remains controversial, with some experts advocating universal random testing and others recommending selective testing based on risk factors 7
• Consider prescribing naloxone to patients receiving ≥50 morphine milligram equivalents, especially if concurrent benzodiazepines or gabapentinoids are prescribed 1

Opioid use disorder treatment:

• More frequent monitoring (monthly or more) is appropriate for patients receiving medication-assisted treatment 3
• UDS helps assess for polysubstance use and treatment adherence 1

Patients with HIV:

• In one study, 62% of HIV patients prescribed opioids for chronic pain had problematic use detected primarily by UDS, supporting universal baseline and periodic testing in this population 1

Common Pitfalls to Avoid

• Do not rely solely on patient self-report or clinical prediction to identify substance use, as both have been shown to be unreliable 1
• Do not test for substances where results would not affect patient management or have unclear clinical implications 1
• Do not assume standard immunoassays detect all opioids - they miss most synthetic opioids 1, 4
• Do not interpret positive immunoassays as definitive without considering false positive causes and obtaining confirmatory testing when results are unexpected 1, 2
• Do not use UDS results in isolation to diagnose substance use disorder - clinical assessment is required 1