Pharmaceutical

Adderall

75% dextroamphetamine / 25% levoamphetamine

Evidence TierAWADA PROHIBITED

tuneTypical Dose

5-30 mg daily (prescription-dependent)

watchEffect Window

Immediate (30-60 minutes) for symptom relief. XR provides 8-12 hour coverage.

lockCompliance

WADA PROHIBITED

Overview

Clinical Summary

Adderall is a prescription mixed amphetamine-salt stimulant for ADHD and narcolepsy. It is used clinically to improve attention, impulse control, and daytime wakefulness.

Randomized trials show improved core ADHD symptoms, including attention and hyperactivity, with functional gains in academic and work performance measures. It reduces excessive daytime sleepiness in narcolepsy. Minority research examines augmentation in treatment-resistant depression and cognitive rehabilitation, but these uses depend on clinical context and carry meaningful risk tradeoffs.

Potent CNS stimulant that increases synaptic dopamine and norepinephrine via vesicular release promotion and reuptake inhibition. TAAR1 agonist.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Highly effective reduction of core ADHD symptoms (inattention, hyperactivity, impulsivity)

Secondary Outcomes

  • Maintains wakefulness in narcolepsy
  • Modest sustained-attention improvement in healthy adults (off-label, controversial)

Safety

Contraindications and Interactions

Contraindications

  • Cardiovascular disease
  • Hypertension
  • Glaucoma
  • Hyperthyroidism
  • MAOIs within 14 days
  • History of drug abuse
  • Severe anxiety

Side effects

  • Appetite suppression
  • Insomnia
  • Dry mouth
  • Increased heart rate/BP
  • Anxiety
  • Irritability

Interactions

  • MAOIs (absolute contraindication)
  • SSRIs (serotonin syndrome)
  • Proton pump inhibitors (increased absorption)
  • Vitamin C/acidifying agents (decreased effect)

Avoid if

  • History of substance use disorder
  • Cardiac anomalies
  • Concurrent MAOI use
  • Severe anxiety disorders

Evidence

Study-level References

adderall-SRC-001Meta-analysis
Sourceopen_in_new

Faraone SV, Biederman J. "Efficacy of mixed amphetamine salts for ADHD." 2002.

Population: Children and Adults with ADHD

Key findings: Confirms high efficacy and established safety profile for labeled indications.

Paper content

Confirms high efficacy and established safety profile for labeled indications.

adderall-SRC-002Systematic review and network meta-analysis.
Sourceopen_in_new

Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738. doi:10.1016/S2215-0366(18)30269-4. PMID:30097390.

Population: Children, adolescents, and adults with ADHD across 133 double-blind RCTs.

Dose protocol: Network meta-analysis of 133 double-blind RCTs across ADHD medications

Key findings: Amphetamines identified as the preferred first-choice medication for adults with ADHD based on combined efficacy and tolerability. Methylphenidate preferred for children and adolescents.

Notes: Published in Lancet Psychiatry. The most comprehensive comparative effectiveness analysis for ADHD pharmacotherapy.

Paper content

This landmark network meta-analysis of 133 double-blind RCTs (over 18,000 participants) compared ADHD medications across age groups. For adults, amphetamines were identified as the preferred first-choice medication based on combined efficacy and tolerability profiles. For children and adolescents, methylphenidate was preferred. This is one of the most comprehensive comparative effectiveness analyses for ADHD pharmacotherapy, published in Lancet Psychiatry, and directly supports amphetamine-class agents as first-line treatment in adults.

adderall-SRC-003Cochrane systematic review and meta-analysis.
Sourceopen_in_new

Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018;8(8):CD007813. doi:10.1002/14651858.CD007813.pub3. PMID:30091808.

Population: Adults (18+) with ADHD across 19 RCTs.

Dose protocol: Cochrane review of 19 RCTs. Dexamphetamine 10-22 mg/day, lisdexamfetamine 30-70 mg/day, mixed amphetamine salts 12.5-80 mg/day. Mean study duration 5.3 weeks.

Key findings: Amphetamines significantly improved ADHD symptom severity but did not improve treatment retention. Higher adverse event-related dropout in amphetamine groups. Evidence quality low to very low.

Notes: Cochrane-level evidence. Covers all three amphetamine formulations used for adult ADHD.

Paper content

This Cochrane review of 19 RCTs (2,521 adults with ADHD) found that amphetamines significantly reduced ADHD symptom severity on both clinician- and self-rated measures in the short term. However, amphetamines did not improve treatment retention and were associated with higher dropout rates due to adverse events compared to placebo. Evidence quality was rated low to very low. The review covers dexamphetamine, lisdexamfetamine, and mixed amphetamine salts, providing the most comprehensive Cochrane-level evidence synthesis for amphetamines in adult ADHD.

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