What is the longest acting amphetamine (amphetamine) stimulant?

Longest Acting Amphetamine Stimulant

Lisdexamfetamine dimesylate (Vyvanse) is the longest acting amphetamine stimulant with effects lasting up to 14 hours in adults and 13 hours in children. 1, 2

Comparison of Long-Acting Stimulant Options

Amphetamine-Based Stimulants

• Lisdexamfetamine dimesylate (Vyvanse) is a prodrug that is converted to dextroamphetamine primarily by red blood cells, providing the longest duration of action among amphetamine stimulants at 13-14 hours 1, 2, 3
• Extended-release mixed amphetamine salts (Adderall XR) have effects lasting approximately 8-9 hours, which is significantly shorter than lisdexamfetamine 4
• Dextroamphetamine extended-release (Dexedrine Spansules) typically provides 8-9 hours of symptom control 4

Methylphenidate-Based Stimulants (For Comparison)

• OROS-MPH (Concerta) utilizes an osmotic pump system that provides continuous action over a 12-hour period 4
• Standard extended-release methylphenidate formulations provide approximately 4-6 hours of clinical action 4
• Immediate-release methylphenidate has the shortest duration, with effects lasting only 4-6 hours 4

Pharmacokinetic Properties of Lisdexamfetamine

• Lisdexamfetamine is a therapeutically inactive prodrug that is converted to L-lysine and active d-amphetamine following oral ingestion 5
• The conversion occurs primarily in the blood via hydrolytic enzymes located on erythrocytes, making its absorption unaffected by gastrointestinal pH and variations in transit times 2, 3
• Time to reach maximum plasma concentration (Tmax) for lisdexamfetamine is about 7 hours, compared to approximately 3 hours for immediate-release amphetamine formulations 6
• The mean elimination half-life for d-amphetamine is 10 hours in adults, 11 hours in adolescents, and 9 hours in children aged 6-12 years 6

Clinical Advantages of Lisdexamfetamine

• The prodrug formulation provides consistent plasma concentrations throughout the day, avoiding the "roller-coaster effect" seen with shorter-acting stimulants 4, 2
• Once-daily dosing improves medication adherence and reduces stigma associated with in-school dosing 4
• The extended duration of action (up to 14 hours) provides symptom control that extends into evening hours, which can be particularly beneficial for adults who need coverage for work and evening activities 1, 2
• Lisdexamfetamine has demonstrated lower abuse potential compared to immediate-release amphetamine formulations due to its prodrug nature 5, 3

Practical Considerations

• Lisdexamfetamine is available in capsule form that can be opened and contents sprinkled on applesauce, which results in comparable absorption to the intact capsule 6
• The safety profile is consistent with other long-acting stimulants, with common side effects including decreased appetite, insomnia, headache, and irritability 2
• For patients who have difficulty swallowing pills, various extended-release amphetamine formulations are available as chewable tablets, sprinklable capsules, liquids, and transdermal patches 7

Potential Drawbacks

• Like all stimulants, lisdexamfetamine may cause side effects including decreased appetite, insomnia, and cardiovascular effects 2
• Some patients may not require the full 13-14 hour coverage that lisdexamfetamine provides 4
• In special populations such as adolescents with substance abuse concerns, non-stimulant medications may be preferable despite the shorter duration of action 8

In conclusion, when duration of action is the primary consideration, lisdexamfetamine dimesylate (Vyvanse) is clearly the longest-acting amphetamine stimulant currently available, with clinical effects lasting up to 14 hours in adults and 13 hours in children.