Vyvanse Week by Week: What to Expect in Your First Month on Lisdexamfetamine

What the label actually schedules

Vyvanse is a prodrug of dextroamphetamine, taken by mouth [2]. It is approved for ADHD in adults and children 6 and older and for moderate to severe binge eating disorder in adults [2]. Under the label, 30 mg once every morning is the starting dose for both indications [2]. For ADHD, the label permits increases of 10 or 20 mg at about weekly intervals to a recommended range of 30 to 70 mg a day [2]. For BED, it permits 20 mg increases at about weekly intervals to a target of 50 to 70 mg a day [2]. The maximum is 70 mg a day in both cases [2].

The label says to take it in the morning with or without food and to avoid afternoon doses because of insomnia [2]. A capsule can be swallowed whole or opened and mixed with yogurt, water or orange juice and taken immediately; the mixture should not be stored [2]. A single dose should not be divided [2].

Week 1: the starting dose

Week 1 is the 30 mg starting dose [2]. In a 4-week double-blind trial of 420 adults with moderate to severe ADHD, lisdexamfetamine 30, 50 and 70 mg a day all separated from placebo on ADHD-RS scores beginning at week 1 and at each week thereafter [1]. At endpoint, ADHD-RS changes were -8.2 with placebo and -16.2, -17.4 and -18.6 with 30, 50 and 70 mg, with no differences between the three doses [1]. Clinical improvement on the CGI-I scale was 29% with placebo and 57%, 62% and 61% with the three doses [1].

A separate laboratory school study of 117 children aged 6 to 12 found significant efficacy from 1.5 hours to 13 hours after a dose [4].

Weeks 2 and 3: the titration decision

The label's weekly increments mean the dose can move during weeks 2 and 3: from 30 mg to 40, 50, 60 or 70 mg for ADHD, or from 30 mg toward 50 to 70 mg for BED [2].

The 4-week adult ADHD trial found no difference in endpoint efficacy between 30, 50 and 70 mg, with the 50 and 70 mg groups reached by forced titration [1].

Week 4: what the 4-week trials measured

By week 4, the main ADHD trials end. In the 420-adult trial, the endpoint results above were the week-4 results [1]. In a 4-week trial of 290 children aged 6 to 12, lisdexamfetamine 30, 50 and 70 mg all improved ADHD-RS-IV scores more than placebo; discontinuations for adverse events were 9% at 30 mg, 5% at 50 mg, 14% at 70 mg and 1% with placebo [3].

The BED trials ran 12 weeks, and their primary endpoint was change in binge eating days per week at weeks 11 and 12 [5]. The treatment differences were -1.35 and -1.66 binge days per week in the two trials, favoring lisdexamfetamine [5].

Side effects over the first month

The label reports these rates from the controlled trials [2]. In the 4-week adult ADHD trial, decreased appetite occurred in 27% vs 2% on placebo, insomnia in 27% vs 8%, and dry mouth in 26% vs 3% [2]. In children 6 to 12, decreased appetite was 39% vs 4% and insomnia 22% vs 3% [2]. In the two 12-week BED trials, dry mouth was 36% vs 7% and insomnia 20% vs 8% [2].

The label also lists mean increases in blood pressure of about 2 to 4 mm Hg and heart rate of about 3 to 6 bpm, with larger increases in some patients, and says to monitor blood pressure and pulse [2]. The label says to avoid Vyvanse in people with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease or other serious cardiac disease, and notes that sudden death has been reported in patients with serious cardiac disease treated with CNS stimulants at recommended ADHD doses [2]. New psychotic or manic symptoms occurred in about 0.1% of stimulant-treated patients vs 0% on placebo in pooled short-term trials [2].

Vyvanse is a Schedule II controlled substance; the boxed warning is abuse, misuse and addiction; misuse can cause overdose and death, and the risk is higher with higher doses or snorting or injection [2]. MAOIs are contraindicated during use and within 14 days of stopping because of hypertensive crisis risk [2]. Serotonergic drugs raise the risk of serotonin syndrome [2]. Severe renal impairment caps the dose at 50 mg a day and end-stage renal disease at 30 mg a day [2].

What the label says to monitor in the first month

Before treatment, the label calls for an assessment for cardiac disease, including history, family history of sudden death or ventricular arrhythmia, and a physical exam, plus evaluation for tics or Tourette's syndrome [2]. Throughout treatment it directs monitoring of blood pressure and pulse, and in pediatric patients close monitoring of height and weight because stimulants are associated with weight loss and slowed growth [2]. In BED, the label says to discontinue Vyvanse if binge eating does not improve [2].