Vyvanse Appetite & Cravings Changes: What the Clinical Evidence Shows

Does Vyvanse change appetite?

Yes, and the label treats it as one of the most common effects of the drug. Decreased appetite appears in the label's list of most common adverse reactions for both ADHD and binge eating disorder [1].

The rates come from 4-week placebo-controlled ADHD trials and two 12-week binge eating disorder trials:

• Children aged 6 to 12 with ADHD: decreased appetite 39% vs 4% on placebo; anorexia 2% vs 0% [1]
• Adolescents aged 13 to 17 with ADHD: decreased appetite 34% vs 3%; anorexia 2% vs 0% [1]
• Adults with ADHD: decreased appetite 27% vs 2%; anorexia 5% vs 0% [1]
• Adults with binge eating disorder: decreased appetite 8% vs 2%, well behind dry mouth (36% vs 7%) and insomnia (20% vs 8%) [1]

The label notes that adverse reaction rates observed in one set of clinical trials cannot be directly compared with rates in another drug's trials and may not reflect rates seen in practice [1].

Vyvanse itself is inactive. It is a prodrug converted to dextroamphetamine mainly in the blood by red blood cells, not by cytochrome P450 enzymes [1]. Amphetamines block reuptake of norepinephrine and dopamine into the presynaptic neuron and increase release of these monoamines; the label states that the exact mode of therapeutic action in ADHD and binge eating disorder is not known [1].

What the binge eating trials show about cravings

The two pivotal trials randomized 383 and 390 adults with moderate to severe binge eating disorder, respectively, to lisdexamfetamine 50 or 70 mg a day or placebo for 12 weeks [2]. The primary endpoint was change from baseline in binge eating days per week at weeks 11 to 12. The treatment difference favored lisdexamfetamine by 1.35 days per week in study 1 (95% CI -1.70 to -1.01) and by 1.66 days per week in study 2 (95% CI -2.04 to -1.28), both P<0.001 [2]. Treatment-emergent adverse events reported by at least 10% of lisdexamfetamine participants were dry mouth, insomnia and headache, and mean pulse rose 4.41 to 6.31 beats per minute [2].

A separate randomized-withdrawal study tested whether the effect holds. Four hundred eighteen adults entered a 12-week open-label phase at 50 or 70 mg; 275 who responded were then randomized to continue lisdexamfetamine (n=137) or switch to placebo (n=138) for up to 26 weeks [3]. Relapse occurred in 3.7% of those who continued (5 of 136) versus 32.1% of those switched to placebo (42 of 131), hazard ratio 0.09 (95% CI 0.04 to 0.23, P<0.001) [3]. Only responders to open-label treatment were randomized, so this is a measure of staying well, not of starting treatment [3].

The label's binge eating disorder schedule starts at 30 mg each morning and rises by 20 mg at roughly weekly intervals to a target of 50 to 70 mg a day, with a maximum of 70 mg, and says to discontinue if binge eating does not improve [1].

One limit on reading these results as a craving effect: the measured outcome was binge eating days, not a hunger or craving score [2]. The trials show fewer binge episodes; they do not quantify how intensely people wanted food in between.

What happens to weight

• Adults with ADHD, 4 weeks: decreased weight 3% vs 0% on placebo [1]
• Children aged 6 to 12, 4 weeks: weight decreased 9% vs 1%; mean weight change was -0.9, -1.9 and -2.5 pounds at 30, 50 and 70 mg, against weight gain on placebo [1]
• Adolescents aged 13 to 17, 4 weeks: weight decreased 9% vs 0% [1]
• Adults with binge eating disorder, 12 weeks: decreased weight 4% vs 0% [1]

Timing: what the pharmacokinetics show

After a capsule taken fasted by children aged 6 to 12, lisdexamfetamine peaks at about 1 hour and dextroamphetamine at about 3.5 hours; food lengthens the time to peak dextroamphetamine by about an hour without changing total exposure or peak concentration [1]. Dextroamphetamine's half-life is about 10 to 11.3 hours in healthy adults and 8.6 to 9.5 hours in children aged 6 to 12 [1]. The label directs morning dosing, with or without food, and says to avoid afternoon doses because of insomnia [1].

A laboratory school study of 117 children found ADHD symptom scores better than placebo from 1.5 through 13 hours after a dose [4]. That study measured attention and behavior, not appetite, so these drug-level and symptom timings do not show how long appetite changes last.

What the label says to watch for

The label states that CNS stimulants are associated with weight loss and slowing of growth rate in pediatric patients, that the 4-week trial in children aged 6 to 12 showed a dose-related decrease in weight while the placebo group gained weight, and that growth in height and weight should be closely monitored; children who are not growing or gaining height or weight as expected may need to have their treatment interrupted [1]. Vyvanse is not recommended in children younger than 6 because they had higher plasma exposure and more adverse reactions such as weight loss at the same dosage [1].