Therapeutic Blood Levels of Adderall
There is no established therapeutic plasma concentration range for Adderall (mixed amphetamine salts) in clinical practice, and therapeutic drug monitoring is not routinely recommended or used for dose adjustment in ADHD treatment.
Why Therapeutic Monitoring Is Not Standard Practice
Amphetamines lack a defined concentration-effect relationship: Unlike tricyclic antidepressants or lithium, there is no consensus therapeutic range for amphetamines that correlates reliably with clinical efficacy or toxicity 1.
Clinical response guides dosing, not blood levels: The 2002 practice parameters from the American Academy of Child and Adolescent Psychiatry emphasize that stimulant dosing is titrated based on behavioral response and tolerability, not plasma concentrations 1.
Amphetamine effects occur during the absorption phase: Behavioral improvements appear within 30 minutes of ingestion and last 3–4 hours for immediate-release formulations, with effects concentrated in the early absorption phase rather than correlating with steady-state levels 1.
Pharmacokinetic Data Available (Not Therapeutic Ranges)
While therapeutic ranges are not established, pharmacokinetic studies provide reference plasma concentrations after standard dosing:
Immediate-Release Adderall (20 mg single dose)
- Peak d-amphetamine concentration (Cmax): approximately 36.6 ng/mL at 3 hours post-dose 2.
- Time to peak (Tmax): approximately 3 hours 2.
- Elimination half-life (T½): approximately 12 hours for both d- and l-amphetamine 2.
Extended-Release Formulations (15 mg sustained-release)
- Peak d-amphetamine concentration: approximately 23.5 ng/mL at 8 hours post-dose 2.
- Tmax: approximately 8 hours 2.
Pediatric Data (SHP465 MAS 6.25 mg in children aged 4–5 years)
- Median Tmax: 7.92 hours for both d- and l-amphetamine at steady state 3.
- Geometric mean T½: 10.4 hours for d-amphetamine and 12.3 hours for l-amphetamine 3.
Urinary Excretion Studies (Not Plasma Levels)
- Following a single 20 mg dose of Adderall, peak urinary amphetamine concentrations ranged from 2645 to 5948 ng/mL, with concentrations ≥500 ng/mL (the forensic cutoff) detected up to 47.5 hours post-dose 4.
- After five consecutive daily 20 mg doses, peak urinary concentrations ranged from 5739 to 19,172 ng/mL, with detectable levels (≥500 ng/mL) persisting up to 60 hours after the last dose 5.
Clinical Implications
Dose titration is empirical: Start with 10 mg once daily in the morning and increase by 5 mg weekly increments up to a maximum of 50 mg/day based on symptom control and adverse effects 1.
Plasma levels do not predict response: The same dose produces highly variable plasma concentrations between individuals due to differences in absorption, pH-dependent renal excretion, and metabolism, yet clinical efficacy is determined by symptom improvement, not blood levels 1, 2.
Monitoring focuses on clinical outcomes: Assess for therapeutic response (improved attention, reduced hyperactivity) and adverse effects (appetite suppression, insomnia, cardiovascular changes) rather than ordering plasma drug levels 1.
When Plasma Levels Might Be Considered (Forensic or Compliance Contexts)
Suspected non-adherence: If therapeutic failure occurs despite adequate dosing, measuring plasma amphetamine can confirm medication ingestion, though this is rarely done in routine ADHD care 1.
Forensic toxicology: Plasma or urine amphetamine levels are used to distinguish therapeutic use from illicit use, with the presence of l-amphetamine (unique to Adderall's 3:1 d:l ratio) differentiating it from pure d-amphetamine formulations or illicit methamphetamine 4, 5.
Common Pitfalls to Avoid
Do not order routine amphetamine levels for dose adjustment: There is no evidence that measuring plasma concentrations improves clinical outcomes in ADHD treatment 1.
Do not assume higher plasma levels equal better efficacy: The "clockwise hysteresis" phenomenon means behavioral effects can disappear even while amphetamine remains in plasma, indicating that peak concentration timing—not absolute level—drives therapeutic response 1.
Recognize that food increases absorption: Both absorption and bioavailability increase after meals, which can affect timing of peak effects but does not necessitate dose changes based on plasma levels 1.