What are the guidelines for the frequency of controlled substance agreements and urine drug screens when prescribing different classes of controlled substances?

Guidelines for Controlled Substance Agreements and Urine Drug Screening Frequency

National Guidelines

For opioid prescribing, perform urine drug testing before initiating therapy and at least annually thereafter, with controlled substance agreements implemented at the start of treatment. 1

Opioid-Specific Requirements

• Baseline urine drug testing is mandatory before starting any opioid therapy for chronic pain to establish reliability of the patient's substance use history 1
• Annual urine drug testing is the minimum standard, though the CDC designates this as a Category B recommendation requiring individual clinical judgment 1
• More frequent testing (every 1-3 months initially, then every 6-12 months) is recommended for stable patients, with provisions for random testing when concerning behaviors emerge 1
• Controlled substance agreements should be established at treatment initiation and used as a clinical tool to facilitate open dialogue about risks and benefits, not as a punitive contract 1

Risk-Stratified Monitoring Approach

The frequency of monitoring should be adjusted based on patient risk level:

• Low-risk patients: At least annual adherence monitoring including detailed interviewing, prescription monitoring program checks, and urine drug screening 1
• Moderate-risk patients: At least semiannual monitoring (every 6 months) with the same comprehensive assessment 1
• High-risk patients: Monitoring every 2-3 months with more frequent visits, including pill counts in addition to standard monitoring 1

Prescription Drug Monitoring Program (PDMP) Requirements

• Check PDMP data when starting opioid therapy and periodically during continuation, with frequency ranging from every prescription to every 3 months 1
• PDMP review is recommended at each encounter prior to prescribing any controlled substance in states with mandatory usage laws 2

Clinical Reassessment Timeline

• Evaluate benefits and harms within 1-4 weeks of starting opioid therapy or dose escalation 1
• Reassess benefits and harms every 3 months or more frequently during continued therapy 1

Non-Opioid Controlled Substances

Stimulants (Schedule II)

• The same controlled substance agreement framework applies to Schedule II stimulants as recommended for opioids in primary care settings 3
• Urine drug screening and PDMP checks should follow similar protocols as opioid prescribing, with baseline testing and periodic monitoring 3
• Monthly follow-up visits are appropriate when enhanced monitoring is needed, such as when unexpected drug test results occur 4

Benzodiazepines

• Avoid concurrent prescribing with opioids whenever possible due to high overdose risk 1
• When prescribed alone, apply similar monitoring principles as opioids, though specific frequency guidelines are less well-defined 1

Gabapentinoids (Pregabalin, Gabapentin)

• Controlled substance agreements are NOT required for pregabalin or gabapentin as these are adjuvant analgesics, not opioids 5
• Standard medication monitoring includes periodic assessment of efficacy and tolerability, without mandatory urine drug testing 5
• PDMP checks are recommended when clinically indicated, particularly if aberrant behavior is suspected 5

Critical Implementation Points

Universal Application Principle

• Apply monitoring policies uniformly to all patients receiving controlled substances ("we do this for everyone") to prevent bias and reduce stigmatization 1
• Random scheduling of urine drug testing is more effective than predictable scheduling when additional monitoring is required, as it reduces opportunities for tampering 1

Response to Abnormal Results

• Never dismiss patients from care based solely on urine drug test results, as this constitutes patient abandonment and creates safety risks 4
• Discuss unexpected results directly with the patient in a non-judgmental manner before making medication changes 4
• The only scenario justifying abrupt discontinuation without taper is confirmed diversion (repeated testing showing the patient is not taking the prescribed medication) 4

Testing Methodology

• Use immunoassay screening first, followed by confirmatory testing only when results are unexpected or will directly inform clinical decisions to reduce costs 6
• Standard immunoassays do not consistently detect hydrocodone, fentanyl, hydromorphone, oxycodone, methadone, or certain benzodiazepines; gas chromatography or mass spectrometry is needed for specific substance identification 1

Common Pitfalls to Avoid

• Do not assume controlled substance agreements give carte blanche to dismiss patients, as non-abandonment principles supersede contractual language 4
• Do not conflate use of non-prescribed substances (like cannabis) with misuse of the prescribed controlled substance; these require separate clinical responses 4
• Avoid testing for substances where clinical implications are unclear (such as THC when prescribing stimulants), as the interaction profile differs from opioid-CNS depressant combinations 4
• False-positive results can occur from poppy seeds, other medications, and laboratory error; false-negative results can occur from nonadherence, diversion, tampering, or test limitations 1

State-Specific Variations

While national guidelines provide the framework above, individual state laws may mandate more stringent requirements, such as:

• Mandatory PDMP checks at every controlled substance prescription 2
• Required urine drug testing at specific intervals 3
• Mandatory controlled substance agreements for all Schedule II prescriptions 3

Clinicians must comply with whichever standard is more stringent—state law or national guidelines—as state regulations supersede professional society recommendations when they impose stricter requirements.