Vyvanse (Lisdexamfetamine Dimesylate) – Clinical Overview
Indications
Vyvanse is FDA-approved for two specific conditions: attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years and older, and moderate to severe binge eating disorder (BED) in adults. 1
- For ADHD, lisdexamfetamine has demonstrated efficacy in both pediatric patients (6–12 years) and adults, with significant reductions in ADHD Rating Scale Version IV scores compared to placebo (P < 0.001). 2
- For BED, two pivotal 12-week phase III trials showed significantly greater reduction in binge eating days per week with lisdexamfetamine 50–70 mg/day versus placebo, making it the only FDA-approved medication for this indication. 3
- Vyvanse is NOT indicated for weight loss; use of sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events, and the safety and effectiveness of lisdexamfetamine for obesity treatment have not been established. 1
Mechanism of Action & Pharmacokinetics
Lisdexamfetamine is a therapeutically inactive prodrug that requires enzymatic hydrolysis in the blood to release active d-amphetamine and L-lysine. 4 This conversion occurs via rate-limited hydrolysis by erythrocyte enzymes, resulting in delayed absorption compared to immediate-release amphetamine formulations. 4
- The prodrug design provides sustained therapeutic coverage throughout the day with a single morning dose, with onset of action within 1–2 hours post-dose and duration of effect up to 12–13 hours. 5, 2
- Because alternative routes of administration (nasal, intravenous) do not bypass the requirement for enzymatic conversion, lisdexamfetamine demonstrates lower abuse potential; studies in known stimulant abusers showed it did not produce significant elevation of drug-liking scores compared to immediate-release d-amphetamine at equivalent doses. 5, 2
- Lisdexamfetamine follows linear pharmacokinetics at therapeutic doses (30–70 mg). 2
Dosing Regimen
ADHD (Adults and Pediatric Patients ≥6 Years)
Start at 30 mg orally once every morning. 1
- Titrate in increments of 10 mg or 20 mg weekly based on symptom response and tolerability. 1
- Recommended therapeutic range: 30–70 mg per day. 1
- Maximum dose: 70 mg per day. 1
- Amphetamine-based stimulants, including lisdexamfetamine, are preferred for adults based on comparative efficacy studies, achieving 70–80% response rates. 6, 7
Binge Eating Disorder (Adults)
Start at 30 mg orally once every morning. 1
- Titrate in increments of 20 mg weekly. 1
- Recommended therapeutic range: 50–70 mg per day. 1
- Maximum dose: 70 mg per day. 1
Renal Impairment Adjustments
- Severe renal impairment (eGFR 15–29 mL/min/1.73 m²): Maximum dose is 50 mg/day. 1
- End-stage renal disease (ESRD; eGFR <15 mL/min/1.73 m²): Maximum dose is 30 mg/day. 1
Administration
- Administer once daily in the morning to minimize insomnia risk. 6
- Capsules may be swallowed whole or opened and the entire contents dissolved in water and consumed immediately. 1
Contraindications
Absolute contraindications include: 1
- Known hypersensitivity to amphetamine products or other ingredients in lisdexamfetamine.
- Current use of monoamine oxidase inhibitors (MAOIs) or within 14 days of the last MAOI dose (risk of hypertensive crisis). 1, 6
- Active psychotic disorder. 6
- Symptomatic cardiovascular disease, including known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, or coronary artery disease. 1
- Uncontrolled hypertension. 6
- Glaucoma. 6
- Hyperthyroidism. 6
- History of illicit stimulant abuse (unless treatment is provided in a controlled setting). 6
Relative contraindications requiring caution: 6
- History of substance-use disorder: Consider long-acting formulations with lower abuse potential and implement close monitoring.
- Seizure disorder: Ensure stability on anticonvulsant therapy before initiating.
- Unstable mood disorder: Stabilize mood first, though some patients with secondary depression may improve once ADHD symptoms are treated.
- Marked anxiety: Recent data indicate stimulants do not necessarily exacerbate anxiety and may improve comorbid anxiety symptoms.
Adverse Effects
Most Common (Incidence ≥5% and at Least Twice Placebo Rate)
In pediatric patients (6–17 years) and/or adults with ADHD: 1
- Decreased appetite and anorexia
- Insomnia
- Upper abdominal pain
- Headache
- Irritability
- Decreased weight
- Dry mouth
- Nausea and vomiting
- Dizziness
- Anxiety
- Diarrhea
In adults with BED: 3
- Dry mouth
- Headache
- Insomnia
Most treatment-emergent adverse events (TEAEs) were of mild or moderate intensity and infrequently led to discontinuation. 3
Serious Adverse Effects
- Cardiovascular effects: Modest increases in blood pressure (1–4 mm Hg) and heart rate (1–2 beats per minute) are statistically significant but generally clinically insignificant. 7
- Growth suppression: Chronic stimulant use, particularly at higher doses, can suppress growth by roughly 1–2 cm from predicted adult height in pediatric patients. 6
- Psychiatric symptoms: Rare but serious events include hallucinations, psychotic symptoms, and manic episodes; these require immediate discontinuation. 6, 1
- Peripheral vasculopathy, including Raynaud's phenomenon: Careful observation for digital changes is necessary during treatment. 1
- Serotonin syndrome: Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans) or during overdose situations. 1
Monitoring Recommendations
Baseline Assessment (Prior to Initiation)
Perform a comprehensive cardiovascular evaluation: 6
- Measure blood pressure and pulse.
- Obtain detailed personal and family cardiac history, specifically screening for sudden cardiac death in relatives younger than 50 years, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, Long QT syndrome, unexplained syncope or seizures, and cardiovascular symptoms (chest pain, palpitations).
- If any cardiac risk factors are present, obtain ECG and consider cardiology referral before starting treatment.
Screen for psychiatric comorbidities: 6
- Assess for risk factors for developing a manic episode, comorbid depression, anxiety, bipolar disorder, and substance-use disorders using validated tools.
Document baseline measurements: 6
- Height and weight (particularly in pediatric patients).
- All prior ADHD-related treatments (medications, doses, duration, response, side effects, adherence).
During Titration (First 4–6 Weeks)
Weekly monitoring includes: 6, 7
- Blood pressure and pulse at each dose adjustment.
- ADHD symptom rating scales (patient and informant reports).
- Sleep quality and appetite changes.
- Suicidality screening (particularly when comorbid depression exists).
Maintenance Phase
For adults: 6
- Check blood pressure and pulse quarterly.
For children and adolescents: 6
- Perform annual vital-sign assessment.
- Measure height and weight at every visit to monitor growth effects.
Ongoing assessments: 6
- Functional improvement across home, school/work, and social settings.
- Emergence or worsening of tics or Tourette's syndrome.
- Signs of peripheral vasculopathy (digital changes).
- Tolerance development (rare with appropriate dosing).
Critical Clinical Pearls
- Do not rely solely on weight-adjusted (mg/kg) dosing; systematic titration to the lowest effective dose that yields clinical benefit is preferred. 6
- Lisdexamfetamine is associated with greater appetite suppression and sleep disturbance compared to methylphenidate, reflecting its longer elimination half-life. 6
- If the top recommended dose (70 mg) does not help, more is not necessarily better; consider a change in drug class or environmental/psychosocial intervention instead. 6
- Approximately 40% of patients respond to both methylphenidate and amphetamine classes, while another 40% respond to only one; if inadequate response occurs after adequate lisdexamfetamine trial, switch to methylphenidate-based stimulants before considering non-stimulants. 6, 7
- Pediatric patients younger than 6 years experienced more long-term weight loss than patients 6 years and older; use in this age group requires careful risk-benefit assessment. 1