Amphetamine formulations parallel the methylphenidate family but with one important pharmacologic addition: amphetamine releases dopamine and norepinephrine directly from presynaptic vesicles, on top of the reuptake inhibition shared with methylphenidate. The clinical effect is similar, but the mechanism is more aggressive.
- Class
- CNS stimulant (amphetamine family)
- Mechanism
- DAT + NET reuptake inhibition + presynaptic vesicular release of DA/NE (via VMAT2 reversal)
- Typical dose
- Adderall IR 5-30 mg/day in divided doses; Adderall XR 5-30 mg daily; Vyvanse 30-70 mg daily
- Half-life
- IR ~10 hours; XR 10-12 hour coverage; Vyvanse 13-14 hour coverage (lisdexamfetamine converted to dextroamphetamine in blood)
- FDA indications
- ADHD, binge eating disorder (lisdexamfetamine specifically), narcolepsy
- Key adverse effects
- Appetite suppression, insomnia, irritability, BP/HR elevation, weight loss, growth slowing in children
- Representative agents
- Mixed amphetamine salts (Adderall IR, Adderall XR), dextroamphetamine (Dexedrine), lisdexamfetamine (Vyvanse — prodrug)
Black box: Schedule II — abuse potential. Cardiovascular events in structural heart disease.
Lisdexamfetamine (Vyvanse) is a prodrug requiring enzymatic activation by red blood cells — cannot be activated by injection or insufflation, making it abuse-deterrent. Often preferred when abuse/diversion is a concern.
Adderall — mixed amphetamine salts. The standard formulation contains 75 percent d-amphetamine and 25 percent l-amphetamine. The mixed enantiomers may produce a slightly different clinical response than pure d-amphetamine for some patients. Available as Adderall IR (4-6 hour duration) and Adderall XR (10-12 hours).
Dexedrine — pure d-amphetamine. The older single-enantiomer form. Less commonly prescribed now than mixed salts but still in use.
Vyvanse (lisdexamfetamine) — the prodrug. This is the pharmacologically clever member of the family. Lisdexamfetamine is pharmacologically inactive until red blood cell enzymes cleave the L-lysine attached to dextroamphetamine. Because the activation requires enzymatic processing, lisdexamfetamine cannot be activated by snorting or injecting — abuse-deterrent by design. Onset is steady and gradual; duration is 13-14 hours. For patients with abuse risk in their history or their environment, Vyvanse is often the preferred amphetamine.
Amphetamines differ from methylphenidate by an additional mechanism — they actively release catecholamines, not just block reuptake — giving a somewhat stronger effect.
Mechanism note: Amphetamines add active catecholamine release to reuptake blockade — a modestly stronger effect than methylphenidate. Lisdexamfetamine's prodrug design is the cleanest answer to the abuse-liability problem.
Vyvanse also carries a unique FDA indication: binge eating disorder. The evidence supports specific binge-day reduction beyond what general appetite suppression would explain. For the patient with BED, Vyvanse is FDA-approved at moderate doses (typically 50-70 mg daily). This is not a weight-loss indication; it is specifically for binge eating reduction.
Side effects across the amphetamine family include appetite suppression (often significant), insomnia, irritability, increased BP and HR. Monitor growth in pediatric patients. Counsel about adequate hydration and nutrition.
The methylphenidate-vs-amphetamine choice is often empirical — try one, switch if inadequate. The Vyvanse-vs-Adderall choice within amphetamines often comes down to abuse risk and cost.
- Cost
- Adderall IR/XR generic ~$15-40/month. Dexedrine generic ~$30-60/month. Vyvanse generic (recent) ~$50-200/month; brand ~$400+/month.
- Generic status
- Adderall/Dexedrine generic for years. Vyvanse generic since 2023.
- Formulary typical
- Generics: Tier 1-2. Vyvanse brand: Tier 3 with PA.
- Access friction
- Schedule II restrictions (see methylphenidate). Stimulant shortages have particularly affected amphetamine formulations 2022-2024. Vyvanse generic supply has been variable since launch.
Prescriber tip: For abuse-deterrence concerns, lisdexamfetamine (Vyvanse) is the choice — generic now available though supply variable. For binge eating disorder, Vyvanse is the FDA-approved option.