Vyvanse Sleep Architecture Impact: What the Clinical Evidence Shows

What the Vyvanse label reports about sleep

The label reports insomnia across Vyvanse trial populations, and the rates are high enough to matter. In the 4-week adult ADHD trial (358 people on Vyvanse, 62 on placebo), insomnia was reported by 27% versus 8% [1]. In children aged 6 to 12 the figures were 22% versus 3%, and in adolescents aged 13 to 17, 13% versus 4% [1]. In the two 12-week binge eating disorder trials (373 on Vyvanse, 372 on placebo), insomnia was 20% versus 8%, and it was one of three adverse events reported by 10% or more of Vyvanse participants in those trials, alongside dry mouth and headache [1][3].

Insomnia was also the most frequently reported adverse reaction associated with stopping treatment in the adult ADHD trial (8 of 358 people, 2%); overall, 6% of Vyvanse-treated adults discontinued for adverse reactions versus 2% on placebo [1].

The Vyvanse label instructs morning dosing with or without food and says to avoid afternoon doses because of the potential for insomnia [1].

Timing of a dose

Lisdexamfetamine is inactive as swallowed. It is converted to dextroamphetamine mainly in the blood by red blood cells, not by cytochrome P450 enzymes [1]. In fasting children aged 6 to 12, dextroamphetamine reaches peak plasma levels about 3.5 hours after a capsule, and food delays that peak by roughly an hour without changing total exposure [1]. The half-life of dextroamphetamine is about 10 to 11.3 hours in healthy adults and 8.6 to 9.5 hours in children aged 6 to 12 [1].

What objective sleep studies show

The broadest synthesis of measured sleep in children on stimulants is a 2015 meta-analysis in Pediatrics. It pooled 9 studies with 246 children and adolescents with ADHD who were randomized to stimulants and had objective sleep measurement. It found that stimulants lengthened sleep latency (effect size 0.54), reduced sleep efficiency (effect size -0.32) and shortened total sleep time (effect size -0.59); the authors concluded that youth had worse sleep on stimulant medication [4]. The effect of medication was less evident when youth had been taking it longer [4]. The abstract reports these results for stimulants as a group, not for lisdexamfetamine separately [4].

The lisdexamfetamine-specific data come mainly from trial adverse-event reporting. In a laboratory school study, children aged 6 to 12 with ADHD went through open-label dose optimization at 30, 50 or 70 mg; after that, 117 were randomized to a placebo-controlled crossover phase. Efficacy was maintained from 1.5 hours to 13 hours after the dose, and insomnia was reported in 27% of children during dose optimization [2]. In the adult ADHD trial of 420 people, the commonly reported adverse events were dry mouth, decreased appetite and insomnia [5].

What the trials measured, and what they did not

The Vyvanse trials in the label recorded sleep as a reported adverse event, insomnia, and insomnia appears in every Vyvanse trial population listed there [1]. The label does not describe effects on REM or slow-wave sleep [1]. The pooled stimulant analysis above reported sleep latency, sleep efficiency and total sleep time [4].

On mechanism, amphetamines block reuptake of norepinephrine and dopamine into the presynaptic neuron and increase release of both, and the exact mode of therapeutic action in ADHD and binge eating disorder is not known [1].

What guidance exists for sleep problems in ADHD

A 2013 review of sleep problems in youths with ADHD recommended healthy sleep practices as the foundation of management and behavioral interventions as first-line treatment for insomnia, while noting that further randomized trial evidence was needed. Among medications, randomized trials supported melatonin for reducing sleep-onset delay, with more limited evidence for other drugs [6].