Out Of The Pipeline

Lisdexamfetamine for ADHD

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Extended-action psychostimulant offers daylong coverage and has comparatively low abuse potential.



Lisdexamfetamine—FDA-approved to treat attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 12 (Table 1)—reduces ADHD symptoms during and after school and may be less likely to be abused than other psychostimulants, particularly immediate-release preparations, clinical data suggest.

Table 1

Lisdexamfetamine: Fast facts

Brand name: Vyvanse
Indication: ADHD in children ages 6 to 12
Approval date: February 23, 2007
Manufacturers: New River Pharmaceuticals and Shire
Dosing forms: 30-, 50-, and 70-mg capsules
Recommended dosage: Start at 30 mg/d. If necessary, titrate by 20 mg every 3 to 7 days to a maximum 70 mg/d.

Clinical implications

Because it is effective for about 12 hours, lisdexamfetamine might improve the child’s ability to complete homework and participate in extracurricular activities, which in turn might enhance academic performance and/or socialization skills.

Lisdexamfetamine could help the child with ADHD who shows no contraindications to the drug —particularly if he or she needs daylong coverage.

How it works

Lisdexamfetamine—a dextroamphetamine derivative—is rapidly absorbed and converted to dextroamphetamine, which is believed to exert therapeutic effect by:

  • blocking norepinephrine and dopamine reuptake into presynaptic neurons
  • increasing the neurotransmitters’ release into the extraneuronal space.

The medication’s amphetamine release is highly predictable, which contributes to its therapeutic benefit in ADHD. Amphetamine is released through GI metabolism of lisdexamfetamine, which produces the active d-amphetamine moiety that reaches the bloodstream. The medication is derived from d-amphetamine, with negligible amounts of lysine cleaved.

Lisdexamfetamine requires in vivo metabolism (in the GI tract) to its active constituent d-amphetamine. As a result, the medication will not produce high d-amphetamine blood levels—and should not cause euphoria or other reinforcing effects—if injected or snorted. Its abuse potential is lower overall compared with immediate-release psychostimulant formulations.


Dextroamphetamine’s plasma elimination half-life is approximately 9½ hours—which accounts for lisdexamfetamine’s extended action. The drug reaches steady-state concentrations in 2 to 3 days.

Food does not affect absorption and delays maximum concentration by 1 hour or less, so taking lisdexamfetamine during breakfast should not slow its therapeutic effect. Because dextroamphetamine reaches maximum concentration in approximately 3½ hours, the medication should take effect by the time the child gets to school. In one randomized, phase-2 trial, children with ADHD who received lisdexamfetamine, 30 to 70 mg/d, showed overall improvement within 2 hours after dosing.1


Lisdexamfetamine reduced ADHD symptoms in 2 double-blind studies: a phase-2 crossover study and a phase-3 random-dose trial.

Phase-2 crossover study.2 Fifty-two children ages 6 to 12 with combined or hyperactive-impulsive type ADHD received extended-release mixed amphetamine salts (MAS) for 3 weeks. Subjects received 10 mg/d or dosages titrated to 20 or 30 mg/d based on response to medication.

The youths then were divided into 3 groups based on optimal MAS dosage and received 3 treatments for 1 week each:

  • group 1: placebo; MAS, 10 mg/d; lisdexamfetamine, 30 mg/d
  • group 2: placebo; MAS, 20 mg/d; lisdexamfetamine, 50 mg/d
  • group 3: placebo; MAS, 30 mg/d; lisdexamfetamine, 70 mg/d.

While taking lisdexamfetamine or MAS, subjects showed similar improvement in behavior, based on Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores, and inattention, based on SKAMP and Permanent Product Measure of Performance scores.

Both psychostimulants outperformed placebo in both measures, and both improved behavior more decisively than inattention. Based on post-hoc analysis, improvement 12 hours after dosing was more substantial with lisdexamfetamine than with MAS.

Phase-3 random-dose trial.3 A total of 290 children ages 6 to 12 with combined or hyperactive-impulsive type ADHD were “washed out” from prior medications over 1 week, then received lisdexamfetamine or placebo for 4 weeks. Treatment-group children were started at 30 mg/d; some received dosages titrated at random to 50 or 70 mg/d in weekly 20-mg increments.

Over 4 weeks, ADHD Rating Scale Version IV (ADHD-RS-IV) scores fell 50% to 59% among the 3 lisdexamfetamine dosage groups, compared with a 15% reduction in the placebo group. Substantial ADHD-RS-IV score improvements after 1 week of lisdexamfetamine were maintained throughout the trial, suggesting the medication sustains ADHD symptom improvement. Controlled trials have not addressed lisdexamfetamine use >4 weeks, however.

Based on parents’ and guardians’ reports, treatment-group patients’ ADHD symptoms were notably less severe at 10 AM, 2 PM, and 6 PM compared with placebo-group children.3 This suggests that lisdexamfetamine offers a daylong therapeutic effect.


In the phase-3 study,3 162 of 218 (74%) children receiving any dosage of lisdexamfetamine reported an adverse event, compared with 34 of 72 (47%) children in the placebo group. Overall, 39% of lisdexamfetamine-group patients reported decreased appetite. Also common were insomnia, headaches, irritability, upper abdominal pain, vomiting, and weight loss (Table 2).


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