amphetamine/dextroamphetamine

General Information

Amphetamine/dextroamphetamine (mixed amphetamine salts) is a Schedule II stimulant used as a first-line medication option for ADHD. Benefits are best assessed in functional terms (task completion, fewer mistakes, improved driving attention) rather than subjective “energy.”

Formulation selection determines onset and duration. Immediate-release products emphasize flexibility, while extended-release products provide once-daily morning dosing and reduce midday dosing burden.

In serious mental illness, stimulants can worsen insomnia, anxiety, irritability, mania, or psychosis in susceptible patients. Clinicians typically confirm ADHD diagnosis, ensure mood/psychosis is stable first, and titrate conservatively with close follow-up.

The amphetamine/dextroamphetamine compare view, the evidence feed, and the print page can support shared decision-making about safe use and monitoring.

Common pitfalls are late-day dosing that disrupts sleep, titration that ignores appetite loss and anxiety, and under-recognition of substance use or bipolar spectrum illness. Success depends on matching duration to the impairment window and monitoring for cardiovascular and psychiatric activation.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Promotes release of dopamine and norepinephrine and also inhibits reuptake, increasing catecholamine signaling in circuits relevant to attention and impulse control.

Clinical benefit can be rapid; measure response with concrete targets (work output, fewer errors, less impulsive behavior) and reassess after each dose change.

Because it is activating, it can worsen insomnia and anxiety when dosing is late or titration is too aggressive.

• Increases dopamine and norepinephrine via release and reuptake inhibition.
• Central sympathomimetic effects drive both benefit and adverse reactions.

Metabolism and Pharmacokinetics

• Metabolism includes CYP2D6 (partial) plus other oxidative pathways; drug interactions can be clinically relevant with CYP2D6 inhibitors.
• Renal elimination is strongly pH-dependent. Acidifying agents can increase urinary excretion and reduce exposure; alkalinizing agents can reduce excretion and prolong effects.
• Half-life varies by formulation and individual factors; monitor duration clinically (early wear off vs late insomnia) when adjusting regimens.

Dosing and Administration

• Doses are typically started low and titrated gradually based on functional improvement and tolerability. Immediate-release products often require BID dosing; extended-release products are typically once daily in the morning.
• Typical adult total daily dosing often falls in the 5–40 mg/day range, but labeled maxima vary by product and indication.
• Late-day dosing is usually avoided to limit insomnia; when evening rebound occurs, formulation or timing is often adjusted before adding sedative medications.
• If response is minimal at reasonable doses, clinicians typically reassess ADHD diagnosis, sleep disorders, anxiety/depression, and substance use rather than escalating indefinitely.

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate (more often during titration).
• Track appetite and weight/BMI; revisit nutrition and meal timing if weight loss occurs.
• Monitor sleep onset and duration; adjust timing/formulation before adding sedatives.
• Monitor for anxiety, agitation, mood elevation, or hallucinations; stop/reassess if symptoms emerge.
• Review misuse/diversion risk and document safe storage counseling.

Sources: DailyMed label(s); guideline statements; network meta-analysis context.

Adverse Effects

Interactions

• Contraindicated with MAO inhibitors; allow adequate washout.
• Urinary acidifying or alkalinizing agents can meaningfully alter exposure and duration; review supplements and OTC products when effects change.
• CYP2D6 inhibitors can increase exposure in some patients; monitor for insomnia, tachycardia, or agitation when combining.
• Additive sympathomimetic effects with decongestants or other stimulants can worsen anxiety and cardiovascular effects.

Other Useful Information

• Anchor titration to function (work/school output, fewer errors, safer driving) rather than subjective energy.
• Screen and treat sleep disorders; insomnia can mimic ADHD and stimulants can worsen delayed sleep phase if timing is late.
• In bipolar spectrum illness or psychosis vulnerability, stabilize the primary illness first and monitor closely for activation.
• For diversion prevention, counsel on locked storage and clear refill policies.

References

1. Adderall (mixed amphetamine salts) prescribing information — DailyMed (2024)
2. Adderall XR (mixed Amphetamine Salts Extended Release) Prescribing Information — DailyMed (2025)
3. Attention deficit hyperactivity disorder (NICE guideline NG87) — NICE (2018)
4. Clinical Practice Guideline FOR THE Diagnosis, Evaluation, AND Treatment OF Attention Deficit/hyperactivity Disorder IN Children AND Adolescents — Pediatrics (2019)
5. Comparative Efficacy AND Tolerability OF Medications FOR Adhd (systematic Review AND Network Meta Analysis) — Lancet Psychiatry (2018)