Why might a urine drug screen (UDS) test negative for amphetamines in a person taking Vyvanse (lisdexamfetamine)?

Why Vyvanse May Not Show Positive on Standard Amphetamine UDS

Yes, there are legitimate reasons why a person taking Vyvanse (lisdexamfetamine) might test negative for amphetamines on a standard urine drug screen, primarily related to timing of metabolism, specimen dilution, and the specific immunoassay cutoff thresholds used.

Understanding Vyvanse Metabolism and Detection

Lisdexamfetamine is a prodrug that must be metabolized to dextroamphetamine (the active form) before it can be detected as amphetamine in urine. 1 This metabolic conversion process means:

• The drug produces only the (S)-enantiomer of amphetamine (dextroamphetamine), not the racemic mixture seen with illicit amphetamine use 1
• Detection depends on adequate metabolic conversion and urinary excretion of the active metabolite
• Individual variations in metabolism can affect the concentration of detectable amphetamine in urine

Primary Reasons for Negative Results Despite Vyvanse Use

Specimen Dilution

Dilution is one of the most common causes of false-negative results, as it lowers drug metabolite concentrations below the screening cutoff values. 2

• Creatinine concentration between 2-20 mg/dL indicates a dilute specimen that may cause false-negatives 2
• Patients may unintentionally dilute their urine by consuming large volumes of fluid to produce a specimen quickly 2
• Even when dilute specimens test positive for one substance, they may simultaneously miss other drugs present at lower concentrations 2
• Always order creatinine and specific gravity with every urine drug test to assess specimen validity 2

Timing and Detection Windows

Most drugs of abuse, including amphetamines, have a detection window of 72 hours or less in urine. 3

• If the patient took their last Vyvanse dose more than 2-3 days before testing, levels may fall below the cutoff threshold
• Detection can be missed due to timing of use relative to testing 3

Immunoassay Limitations and Cutoff Thresholds

Standard immunoassay screening tests are presumptive only and have specific cutoff concentrations (typically 500-1000 ng/mL) that must be exceeded for a positive result. 3, 4

• Lower doses of amphetamine medications may not produce urine concentrations above these cutoffs
• Immunoassay screens are susceptible to cross-reactions and should be considered presumptive until confirmed 4

Critical Clinical Approach

When You Encounter This Scenario:

1. Check specimen validity markers immediately:

   • Review creatinine (should be >20 mg/dL for valid specimen) 2
   • If creatinine is 2-20 mg/dL and test is negative, consider the result indeterminate rather than truly negative 2

2. Consider confirmatory testing with GC-MS:

   • Gas chromatography-mass spectrometry can definitively identify the specific enantiomer composition 5
   • This helps differentiate prescribed dextroamphetamine (from Vyvanse) from illicit amphetamine use 1
   • Confirmatory testing should be used when results will impact clinical decisions 5

3. Verify medication adherence through alternative means:

   • Serial testing over time is more reliable than a single result 2
   • Discuss the complete medication history with the patient 5
   • Consider that a negative result only indicates no detectable use in the past several days 2

Important Caveats

Never make consequential decisions based solely on a single negative immunoassay result without considering the complete clinical context. 5

• A negative result on a dilute specimen does NOT exclude medication use when clinical suspicion remains high 2
• Many providers have inadequate training in interpreting urine drug test results, and incorrect interpretation can have severe consequences 5
• Establish a working relationship with your local toxicologist for consultation on complex results 5
• If results are unexpected, discuss them with laboratory personnel before making clinical decisions 3

The absence of a positive amphetamine screen in a patient prescribed Vyvanse should prompt investigation of specimen validity and timing rather than automatic assumption of non-adherence.