Lisdexamfetamine for ADHD
Extended-action psychostimulant offers daylong coverage and has comparatively low abuse potential.
Although most adverse events were mild to moderate, 9.2% of treatment-group children dropped out because of intolerability, compared with 1.4% of the placebo group. The investigators increased dosages quickly, regardless of efficacy or tolerability,3 which might have increased side-effect incidence among the treatment groups.
In the phase-2 crossover trial,2 adverse event rates were similar among the lisdexamfetamine, extended-release MAS, and placebo groups (15% to 18%). Among youths receiving lisdexamfetamine, 8% reported insomnia and 6% reported appetite loss, compared with 2% and 4% of the MAS group, respectively.
Table 2
Rates of commonly reported adverse effects
during phase-3 lisdexamfetamine (LDX) study
| Adverse effect | LDX 30 mg/d | LDX 50 mg/d* | LDX 70 mg/d* | LDX all dosages | Placebo |
|---|---|---|---|---|---|
| All adverse effects | 72% | 68% | 84% | 74% | 47% |
| Decreased appetite | 37% | 31% | 49% | 39% | 4% |
| Insomnia | 16% | 16% | 25% | 19% | 3% |
| Upper abdominal pain | 14% | 7% | 15% | 12% | 6% |
| Headache | 10% | 10% | 16% | 12% | 10% |
| Irritability | 11% | 8% | 10% | 10% | 0% |
| Vomiting | 7% | 5% | 14% | 9% | 4% |
| Weight loss | 6% | 3% | 19% | 9% | 1% |
| *Dosages were randomly titrated regardless of efficacy or tolerability. | |||||
| Source: Reference 3 | |||||
Safety
Findling et al4 found a larger change in corrected QT interval with lisdexamfetamine (7 to 14 msec) than with extended-release MAS (5 to 10 msec) 5 and 10½ hours after dosing. The authors reasoned that these findings are atypical, and no children suffered serious adverse events during the trial. Nonetheless, more research on whether lisdexamfetamine increases cardiac risk is needed.
In a lethal-dose study in rats,5 oral lisdexamfetamine doses up to 1,000 mg/kg did not result in death, suggesting the medication might undergo saturation kinetics in the GI tract that may protect against overdose or abuse at higher dosages. By comparison, the median lethal oral dosage of d-amphetamine in rats was 96.8 mg/kg.5
Abuse potential
As with other psychostimulants indicated for ADHD, the Drug Enforcement Administration has classified lisdexamfetamine as a schedule II drug, which applies to addictive prescription-only medications with an accepted medical use.
Clinical data suggest, however, that lisdexamfetamine might be less “enjoyable”—and less likely to be abused intravenously, orally, or intranasally—than equipotent d-amphetamine. In an abuse liability study,6 12 adults with histories of stimulant abuse received intravenous immediate-release (IR) d-amphetamine, 10 or 20 mg. Two days later, they received a comparable dose of IV lisdexamfetamine, 25 or 50 mg. The researchers found that:
- Plasma d-amphetamine peaked within 5 minutes after injection, compared with 2 to 3 hours after lisdexamfetamine dosing.
- Subjects who received IR d-amphetamine said they felt euphoria within 15 minutes of injection. By contrast, no one reported euphoria or amphetamine-like subjective effects after receiving lisdexamfetamine.
When asked which medication they would try again, 9 of 12 subjects chose IR d-amphetamine and 1 chose lisdexamfetamine.
In a double-blind, randomized, placebo-controlled study,7 oral lisdexamfetamine, 50 or 100 mg, was not more “likeable” than placebo. Subjects reported “liking” effects with 150 mg of lisdexamfetamine, however, suggesting the medication could be misused or abused at higher-than-therapeutic dosages.
As with other psychostimulants, do not give lisdexamfetamine to youths with preexisting serious structural cardiac abnormalities or other heart problems. Assess patient and family history of heart disease before prescribing this medication.
Do not prescribe lisdexamfetamine to patients taking a monoamine oxidase inhibitor (MAOI). By slowing amphetamine metabolism, these antidepressants intensify amphetamines’ effect on monoamine release, which can cause headaches and lead to hypertensive crisis. Before starting lisdexamfetamine, ask if the patient is taking an MAOI or has taken one within 2 weeks of presentation.
Use caution when prescribing lisdexamfetamine to patients with:
- a comorbid eating disorder or sleep disturbance. Determine whether to address the comorbidity before treating ADHD symptoms, and make sure lisdexamfetamine is not worsening the comorbid symptoms.
- untreated hypertension or other cardiovascular conditions, as stimulant medications can increase blood pressure and heart rate. Watch for significant heart rate and blood pressure changes in patients taking lisdexamfetamine, which probably would not cause sustained blood pressure increase in patients taking antihypertensives.8
Related resources
- Lisdexamfetamine Web site. www.vyvanse.com.
Drug brand names
- Extended-release mixed amphetamine salts • Adderall XR
- Lisdexamfetamine • Vyvanse
Disclosure
Dr. Wilens receives research/grant support from Abbott Laboratories, Eli Lilly and Company, National Institute on Drug Abuse, NeuroSearch, Ortho-McNeil, and Shire; is a speaker for Novartis Pharmaceuticals Corp., Ortho-McNeil, and Shire; and is a consultant to Abbott Laboratories, Eli Lilly and Company, GlaxoSmithKline, National Institute on Drug Abuse, Novartis Pharmaceuticals Corp., Ortho-McNeil, Pfizer, and Shire.
