lisdexamfetamine

General Information

Lisdexamfetamine is a prodrug stimulant converted to dextroamphetamine. It is used as a first-line medication option for ADHD and is also approved for binge eating disorder in adults.

The prodrug design often yields a smoother onset and longer duration for many patients, but it remains a Schedule II controlled substance with meaningful misuse/diversion potential.

In patients with serious mental illness or vulnerability to mania or psychosis, stimulants can worsen insomnia, anxiety, irritability, mania, or psychosis. Diagnosis confirmation and stabilization of the primary illness are often prioritized before stimulant trials, with cautious titration and close follow-up.

The lisdexamfetamine compare view, the evidence feed, and the print page support side-by-side review and patient-friendly counseling on safe use and monitoring.

The most common failures are late-day dosing that disrupts sleep, dose escalation despite appetite loss and anxiety, and under-recognition of bipolar/psychosis vulnerability or substance use. Success depends on matching the regimen to daytime impairment and monitoring for both cardiovascular effects and psychiatric activation.

Mechanism of Action

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

Converted to dextroamphetamine, which increases dopamine and norepinephrine signaling via release and reuptake inhibition.

Clinical benefits can be rapid; response is often evaluated using functional targets (task completion, fewer errors, safer driving) rather than subjective energy.

Activating effects can worsen insomnia and anxiety when dosing is late or titration is too aggressive.

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

Metabolism and Pharmacokinetics

• Prodrug converted by enzymatic hydrolysis (primarily in blood) to active dextroamphetamine; conversion is not CYP-mediated.
• Elimination of active amphetamine is influenced by urinary pH; acidifying agents can increase clearance while alkalinizing agents can prolong effects.
• Clinical duration is often long enough for once-daily dosing; late-day insomnia is often used as a practical marker of excessive duration.

Dosing and Administration

• Usually once daily in the morning; afternoon/evening dosing is typically avoided due to insomnia risk.
• Typical adult starting dose is 30 mg once daily, with titration in 10–20 mg steps (often weekly) based on response and tolerability.
• Typical effective range is 30–70 mg/day; maximum recommended dose is 70 mg/day (label).
• If response is minimal at reasonable doses, ADHD diagnosis, sleep disorders, anxiety/depression, and substance use are often reassessed before continued dose escalation.

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate (more often during titration).
• Appetite and weight/BMI are tracked; nutrition and meal timing are revisited if weight loss occurs.
• Sleep onset and duration are monitored; timing adjustments are often tried before adding sedatives.
• Anxiety, agitation, mood elevation, or hallucinations are monitored; if concerning symptoms emerge, discontinuation and reassessment are common.
• Misuse/diversion risk is reviewed and safe storage counseling is documented.

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

Adverse Effects

Interactions

• Contraindicated with MAO inhibitors; a washout period is typically used.
• Urinary acidifying or alkalinizing agents can meaningfully alter exposure and duration; supplements and OTC products are reviewed when effects change.
• Additive sympathomimetic effects with decongestants or other stimulants can worsen anxiety and cardiovascular effects.

Other Useful Information

• Titration is often anchored to function and revisited after each dose adjustment; “dose chasing” when sleep is deteriorating is generally avoided.
• Sleep disorders are screened and treated; insomnia can mimic ADHD and stimulants can worsen delayed sleep phase if dosing is late.
• In bipolar spectrum illness or psychosis vulnerability, stabilization of the primary illness is typically prioritized, with close monitoring for activation.
• Diversion prevention counseling often includes locked storage, not sharing, and clear refill policies.

References

1. Vyvanse (lisdexamfetamine dimesylate) prescribing information — DailyMed (2025)
2. Attention deficit hyperactivity disorder (NICE guideline NG87) — NICE (2018)
3. Clinical Practice Guideline FOR THE Diagnosis, Evaluation, AND Treatment OF Attention Deficit/hyperactivity Disorder IN Children AND Adolescents — Pediatrics (2019)
4. Comparative Efficacy AND Tolerability OF Medications FOR Adhd (systematic Review AND Network Meta Analysis) — Lancet Psychiatry (2018)