What are the side effects of Vyvanse (lisdexamfetamine)?

Side Effects of Vyvanse (Lisdexamfetamine)

Vyvanse causes predominantly mild to moderate side effects that are generally acceptable and often temporary, with the most common being decreased appetite, insomnia, dry mouth, increased heart rate, headaches, and irritability. 1, 2

Common Side Effects (Occurring in ≥5% of Patients)

Gastrointestinal Effects

• Dry mouth occurs in approximately 36% of patients, making it the most frequent side effect 2
• Decreased appetite affects 8% of patients and is dose-related 2
• Constipation (6%), nausea, vomiting, abdominal pain, and diarrhea also occur 2

Sleep and Neuropsychiatric Effects

• Insomnia affects approximately 20% of patients and represents one of the most common reasons for treatment adjustment 2
• Anxiety (5%), feeling jittery (6%), irritability, and restlessness occur frequently 2
• Headaches are commonly reported across all age groups 1

Cardiovascular Effects

• Increased heart rate and blood pressure occur in most patients, though effects are typically small at the group level 1
• These cardiovascular changes may be clinically significant in patients with preexisting heart disease 1
• Clinical guidelines recommend monitoring pulse and blood pressure regularly during treatment 1

Weight and Growth Effects in Pediatric Patients

Weight loss and growth suppression represent clinically significant concerns requiring careful monitoring. 1, 2

• After 4 weeks of treatment, pediatric patients (ages 6-12) experience mean weight loss of 0.9-2.5 pounds depending on dose (30-70 mg), compared to 1 pound weight gain with placebo 2
• Over 12 months of consistent treatment, pediatric patients show a mean decrease of 13.4 percentile points in age- and sex-normalized body weight 2
• Height growth may be reduced by approximately 2 cm over 3 years of continuous treatment 2
• Adolescents (ages 13-17) experience mean weight loss of 2.7-4.8 pounds after 4 weeks 2
• These effects appear dose-related and require ongoing monitoring of height and weight 1

Serious but Rare Adverse Effects

Cardiovascular Risks

• Sudden death has occurred in patients with structural heart defects or serious heart disease 2
• Patients should be screened for heart problems before initiating treatment 2
• Chest pain, shortness of breath, or fainting during treatment requires immediate medical evaluation 2

Psychiatric Effects

• New or worsening psychotic symptoms (hallucinations, delusions) can occur 2
• New or worsening bipolar illness may emerge 2
• Contrary to earlier concerns, recent evidence suggests psychostimulants may actually decrease suicidal events in ADHD patients rather than increase them 1

Other Serious Effects

• Serotonin syndrome when combined with other serotonergic medications (SSRIs, SNRIs, MAOIs) 2
• Peripheral vasculopathy, including Raynaud's phenomenon 2
• Seizures (postmarketing reports) 2

Postmarketing Adverse Reactions

Additional effects identified after FDA approval include: 2

• Cardiomyopathy
• Visual disturbances (mydriasis, diplopia, blurred vision, accommodation difficulties)
• Eosinophilic hepatitis
• Anaphylactic reactions and angioedema
• Movement disorders (dyskinesia, motor and verbal tics, bruxism)
• Dermatologic effects (Stevens-Johnson Syndrome, urticaria, alopecia, dermatillomania)
• Rhabdomyolysis
• Intestinal ischemia
• Libido changes and prolonged erections

Special Population Considerations

Pregnancy and Lactation

• Lisdexamfetamine is a prodrug converted to dextroamphetamine, with limited specific pregnancy data 1
• Possible small increased risk for preterm birth when use continues in second half of pregnancy (aRR 1.30; 95% CI 1.10-1.55) 1
• Women should not breastfeed while taking Vyvanse; infants should be monitored for irritability, insomnia, and feeding difficulties if exposure occurs 1, 2

Abuse and Dependence Potential

• Vyvanse has high potential for abuse, misuse, and addiction despite its prodrug formulation 2
• Abuse/misuse reports are lower for lisdexamfetamine (13.5%) compared to immediate-release dextroamphetamine/amphetamine (32.5%) in patients aged 6 years and older 3
• The prodrug design provides some protection against abuse compared to immediate-release formulations, but risk remains substantial 4, 3

Clinical Monitoring Requirements

Regular monitoring should include: 1, 2

• Pulse and blood pressure at each visit
• Height and weight in pediatric patients at baseline and regularly throughout treatment
• Assessment for emergence of psychiatric symptoms
• Evaluation for signs of peripheral vasculopathy
• Screening for substance abuse risk before and during treatment 2

Important Clinical Caveats

• Most adverse effects are mild to moderate in severity and often diminish with continued treatment 5, 6
• Discontinuation due to adverse events occurs infrequently (approximately 5% in clinical trials) 2
• Taking medication with food or adjusting timing of administration may help manage gastrointestinal side effects 2
• The therapeutic benefits for ADHD symptoms typically outweigh the side effect burden for most patients when properly monitored 1