What are the options for long-acting amphetamine (amphetamine) medications?

Long-Acting Amphetamine Formulations

The primary long-acting amphetamine options are extended-release mixed amphetamine salts (Adderall XR) providing 8-9 hours of coverage, dextroamphetamine extended-release (Dexedrine Spansules) providing 8-9 hours, and lisdexamfetamine dimesylate (Vyvanse) providing 13-14 hours of coverage, with lisdexamfetamine offering the longest duration of action among amphetamine-based stimulants. 1, 2

Available Long-Acting Amphetamine Formulations

Lisdexamfetamine Dimesylate (Vyvanse)

• Lisdexamfetamine provides the longest duration of amphetamine-based stimulant action at 13-14 hours, making it superior for patients requiring full-day coverage extending into evening hours 1
• This prodrug formulation is converted to dextroamphetamine primarily in red blood cells after oral administration, with conversion occurring in the bloodstream rather than through cytochrome P450 metabolism 2
• The medication is available in capsule form that can be opened and mixed with water or soft food for patients who cannot swallow pills 2
• Dosing typically starts at 30 mg once daily in the morning, with titration up to 70 mg based on response 2
• Clinical trials demonstrate maintained efficacy throughout the day based on assessments at 1,2,3,4.5,6,8,10, and 12 hours post-dose 2

Extended-Release Mixed Amphetamine Salts (Adderall XR)

• Adderall XR provides approximately 8-9 hours of symptom control, which is significantly shorter than lisdexamfetamine but may be sufficient for patients not requiring evening coverage 1
• Available in both immediate-release and extended-release formulations, with typical starting doses of 10 mg daily that can be titrated up to 50 mg 3
• The extended-release capsules contain beads that can be sprinkled on soft food for patients with swallowing difficulties 4
• Contains a mixture of amphetamine salts that inhibit dopamine and norepinephrine transporters, VMAT-2, and monoamine oxidase activity 3

Dextroamphetamine Extended-Release (Dexedrine Spansules)

• Dexedrine Spansules typically provide 8-9 hours of symptom control, similar to Adderall XR in duration 1
• This represents one of the older long-acting amphetamine formulations but remains a viable option 5

Clinical Advantages of Long-Acting Formulations

Adherence and Practical Benefits

• Long-acting formulations eliminate compliance problems with in-school dosing, including school policies prohibiting medication administration, adolescent embarrassment/stigma, and simply forgetting afternoon doses 1
• Once-daily dosing improves medication adherence and reduces stigma associated with taking medication at school or work 1
• Long-acting formulations are associated with probably lower risk of rebound effects compared to immediate-release formulations 1

Duration Considerations

• For patients requiring coverage extending into evening hours for homework, driving, or social activities, lisdexamfetamine's 13-14 hour duration is superior to the 8-9 hour coverage of Adderall XR or Dexedrine Spansules 1
• Some patients may not require the full 13-14 hour coverage that lisdexamfetamine provides, making shorter-acting options appropriate 1
• Plasma concentration troughs with immediate-release stimulants occur at most unstructured times, which long-acting formulations prevent 1

Comparative Efficacy with Methylphenidate

• Both amphetamine and methylphenidate are equally effective first-line stimulant medications for ADHD, with large effect sizes for symptom reduction, but patients who fail to respond to one stimulant class should be switched to the other, as the combined response rate approaches 80-90% when both are tried sequentially 6
• For adults specifically, amphetamine-based stimulants are preferred based on comparative efficacy studies 6
• Individual patients may respond preferentially to either amphetamine or methylphenidate, making sequential trials of both classes essential when the first agent fails 6

Common Adverse Effects and Monitoring

Side Effect Profile

• Common adverse effects include decreased appetite, sleep disturbances, increased blood pressure and pulse, headaches, irritability, and stomach pain 3, 6
• Daily oral amphetamines increase systolic blood pressure by 1.93 mmHg and diastolic blood pressure by 1.84 mmHg, with heart rate increasing by 3.71 beats per minute 7
• These cardiovascular effects are sustained with long-term use (≥8 weeks) and require regular monitoring 7
• Both medications cause statistically significant but usually minor reductions in height and weight gain, which are dose-related and require monitoring 6

Required Monitoring

• Regular monitoring of blood pressure and pulse is required for all amphetamine formulations, as small increases may be clinically relevant in patients with preexisting cardiovascular disease 6
• Track appetite, sleep, and growth parameters, as these are the most common adverse effects requiring dose adjustment 6
• Stimulant medications have not been shown to increase risk of sudden cardiac death after 2-3 years of treatment on average 6

Special Population Considerations

Adolescents

• Before prescribing any amphetamine to an adolescent, screen for substance abuse symptoms, as diversion and misuse are particular concerns in this age group 6
• If substance abuse is identified, assessment of substances must precede ADHD treatment 6
• Prescription refill requests should be monitored for signs of misuse or diversion 6
• For adolescents requiring coverage for driving, longer-acting formulations like lisdexamfetamine or late-afternoon immediate-release supplementation may be helpful 6

Pregnancy

• Therapeutic use of amphetamines during pregnancy does not appear to be associated with major congenital malformations or significant adverse developmental outcomes, according to the American College of Obstetricians and Gynecologists 3

Formulation Options for Swallowing Difficulties

• Multiple amphetamine formulations accommodate patients who cannot swallow pills: lisdexamfetamine capsules can be opened and mixed with water, Adderall XR capsules contain beads that can be sprinkled on soft food, and chewable tablet and liquid formulations are available 2, 4

Critical Pitfalls to Avoid

• Do not assume lack of response to one stimulant class means failure of all stimulants; always trial the alternative class (methylphenidate) before considering non-stimulants 6
• Do not prescribe stimulants for patients whose symptoms do not meet DSM-5 criteria for ADHD 6
• Avoid prescribing lisdexamfetamine late in the day, as its 13-14 hour duration will interfere with sleep if not taken in the morning 1, 2
• Do not overlook the need for cardiovascular screening and monitoring, as amphetamines consistently increase blood pressure and heart rate 7