Adderall XR Rebound Effects When Stopping: What Clinicians and Patients Need to Know

What does the label say follows a dose cut or a stop?

The Adderall tablet label states that the drug may produce physical dependence. It defines this as a state that develops from physiological adaptation to repeated drug use and shows as withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction [1]. After prolonged use of CNS stimulants including Adderall, these include dysphoric mood, depression, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation [1].

The same section states that Adderall may produce tolerance, a reduced response after repeated administration, so that a higher dose is needed for an effect a lower dose once produced [1]. Adderall contains amphetamine, a Schedule II controlled substance [1].

That wording is from the immediate-release Adderall tablet label [1]. Adderall XR is a different product: an extended-release capsule built from the same four amphetamine salts, in two bead types that prolong release, filed under NDA 021303 [2].

How long do the symptoms last, and who gets them?

The dependence section lists the symptoms without a time frame and does not break them down by dose or by how long the drug was taken [1].

How does this relate to the Adderall XR trials?

Adderall XR is indicated for ADHD in adults and children 6 years and older [2]. The trials below measured symptoms while patients were taking it.

A 3-week trial at 47 sites randomized 584 children aged 6 to 12 to a morning dose of 10, 20 or 30 mg of Adderall XR or placebo. Teacher and parent Conners Global Index scores improved significantly in the morning, afternoon and late afternoon at all active doses [3]. In a 4-week dose-escalation trial, 255 adults took Adderall XR 20, 40 or 60 mg a day or placebo. Significant ADHD symptom reduction was seen at all three doses (mean ADHD Rating Scale scores 18.5, 18.4 and 18.5; P=.001 or lower), with a mean effect size of 0.8 [4].

What about children?

The pediatric trial enrolled children aged 6 to 12 [3]. The Adderall XR label says it is not recommended under age 6, citing higher plasma exposure and more adverse reactions such as weight loss [2].