What is the concern if a patient's initial drug screen shows methamphetamine and amphetamine, but they are prescribed dextroamphetamine and amphetamine salts?

Interpreting Methamphetamine and Amphetamine on Drug Screen in Patients Taking Prescribed Amphetamine Salts

A positive drug screen showing both methamphetamine and amphetamine in a patient prescribed dextroamphetamine and amphetamine salts (e.g., Adderall) is expected and does NOT necessarily indicate illicit methamphetamine use, because dextroamphetamine is metabolized to both amphetamine and small amounts of methamphetamine in the body. 1

Understanding the Expected Metabolic Profile

The critical issue is distinguishing legitimate medication use from illicit methamphetamine abuse:

• Prescribed amphetamine salts (dextroamphetamine/amphetamine) will produce positive results for both amphetamine AND methamphetamine on standard immunoassay screens because amphetamine medications can be metabolized to trace amounts of methamphetamine. 1

• Standard immunoassay screening tests are presumptive only and cannot distinguish between prescribed amphetamine use versus illicit methamphetamine use without confirmatory testing. 2

• The ratio of methamphetamine to amphetamine is crucial: Legitimate use of prescription amphetamines typically produces a much higher amphetamine concentration relative to methamphetamine, whereas illicit methamphetamine use produces higher methamphetamine levels with amphetamine as a metabolite. 1, 3

Required Confirmatory Testing Approach

You must order gas chromatography-mass spectrometry (GC-MS) confirmatory testing before making any clinical decisions about illicit drug use:

• GC-MS can identify the specific enantiomer composition (d-methamphetamine vs l-methamphetamine), which helps differentiate illicit methamphetamine (d-enantiomer) from legitimate prescription amphetamine use. 2, 4

• Detection of the d-enantiomer of methamphetamine or a mixture of d- and l-enantiomers clearly establishes use of a controlled substance beyond what would be expected from prescription amphetamine metabolism alone. 4

• Enantiomeric characterization is essential because use of racemic methamphetamine can complicate interpretation due to different metabolism and excretion patterns of l- and d-methamphetamine. 4

Clinical Decision-Making Algorithm

Before concluding illicit drug use, systematically evaluate:

1. Verify the complete medication history, specifically confirming the patient's prescribed amphetamine dose, formulation, and adherence pattern. 2

2. Assess the methamphetamine-to-amphetamine ratio: If amphetamine levels significantly exceed methamphetamine levels, this supports legitimate medication use rather than illicit methamphetamine abuse. 1, 3

3. Order GC-MS confirmatory testing with enantiomer analysis to definitively identify whether d-methamphetamine (illicit) is present beyond what would be expected from prescription amphetamine metabolism. 2, 4

4. Evaluate clinical context: Look for behavioral or mental health symptoms consistent with methamphetamine abuse (paranoia, psychosis, severe weight loss, dental problems, skin picking). 5

5. Consider specimen validity: Check if the sample could have been adulterated, diluted, or substituted. 2

Critical Pitfalls to Avoid

Never make consequential decisions based solely on immunoassay results:

• The American Academy of Pediatrics explicitly states that dismissal from treatment programs or legal actions should not be made based solely on immunoassay results without confirmatory testing and clinical context. 2

• Many providers have inadequate training in interpreting urine drug test results, and incorrect interpretation can have severe consequences, including loss of child custody or legal implications. 2

• False-positives are more likely on screening tests due to cross-reactivity, and a positive screening test without clinical findings suggesting drug use has lower positive predictive value. 2

Additional Considerations for Prescribed Stimulants

Be aware of diversion and misuse risks:

• Diversion of ADHD medication (use for other than intended medical purposes) is a concern, particularly in adolescents and young adults, requiring monitoring of prescription-refill requests for signs of misuse. 5

• Substance abuse assessment should precede ADHD treatment in patients with known substance use history, and consider prescribing medications with lower abuse potential (atomoxetine, extended-release guanfacine) when diversion risk is high. 5

• Multiple positive tests over time, escalating doses without medical justification, or "lost" prescriptions requiring early refills suggest possible misuse or diversion rather than appropriate therapeutic use. 5

When Illicit Use is Confirmed

If confirmatory testing demonstrates illicit methamphetamine use beyond prescribed medication:

• Assess for substance use disorder using validated tools such as the Drug Abuse Screening Test-10, which accurately identifies substance abuse and dependence. 5

• Evidence suggests that methamphetamine use is associated with intrinsically high risk of harm to self and others, requiring more intensive intervention than brief counseling. 5

• Patients with substance dependence require referral for specialized treatment, consideration of pharmacotherapy, and ongoing assessment and support rather than simple dismissal from care. 5