Adderall XR Sleep Architecture Impact: What the Clinical Evidence Shows

What the Adderall XR label records about sleep

Insomnia is one of the most frequent adverse reactions in the Adderall XR trials. In the 3-week pediatric study it was reported by 17% of children aged 6 to 12 taking Adderall XR (n=374) versus 2% on placebo (n=210), and by 12% versus 4% in adolescents aged 13 to 17 who weighed 75 kg or less [1]. In the 4-week adult study, in which participants took Adderall XR 20, 40 or 60 mg/day or placebo, insomnia was reported by 27% of 191 adults on active drug versus 13% of 64 on placebo [1].

The Adderall XR label directs one dose daily on awakening and says to avoid afternoon doses [1]. The immediate-release mixed amphetamine salts label states that late evening doses should be avoided because of the resulting insomnia [3].

Timing and blood levels

Adderall XR is made of two bead types, one immediate-release and one delayed-release, that together extend the release of the same four salts used in the tablets [1]. One 20 mg capsule produces a plasma profile similar to immediate-release 10 mg taken twice, four hours apart, and peak concentrations arrive about 7 hours after the dose, roughly 4 hours later than the immediate-release tablets, which peak at about 3 hours [3][1]. Food does not change the total amount absorbed but delays the peak by about 2.5 hours, to 5.2 to 7.7 hours for d-amphetamine after a 30 mg dose [1].

In adults the mean half-life is about 10 hours for d-amphetamine and about 13 hours for l-amphetamine [1]. The immediate-release label also notes that alkaline urine reduces amphetamine elimination and acidic urine increases it [3].

Sleep problems in ADHD apart from medication

Sleep problems are common in ADHD before any drug is taken. A meta-analysis of 16 studies covering 722 children with ADHD and 638 controls, which excluded medicated children, found higher sleep onset latency on actigraphy and lower sleep efficiency on polysomnography in the ADHD group [4]. A 2015 review of ADHD and sleep reports the same actigraphic pattern of longer sleep onset latency and shorter sleep time, notes that stimulant medications are associated with disrupted sleep, and adds that long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime [5]. The review states that current guidelines recommend assessing sleep before starting medication, with healthy sleep practices as the first-line option for sleep problems [5].