MJB ADHD · Static reading view · Interactive version
Status: sourced · Content checked 2026-10-06
Randomised trials show the medicines reduce core symptoms in adults; a withdrawal trial shows frequent symptom relapse in previously stable adult lisdexamfetamine responders after switching to placebo. Registries suggest wider outcomes may improve, with important caveats.
Three kinds of study answer three different questions:
| Question | Study type | Answer so far |
|---|---|---|
| Do the medicines reduce symptoms? | Randomised controlled trials | Yes, in children and adults R2 |
| Does benefit last only while taking them? | Randomised withdrawal trials | Relapse was frequent after switching stable adult lisdexamfetamine responders to placebo; this does not mean every patient relapses R1 |
| Do they change real-world outcomes? | Registry studies emulating trials | Starting is associated with fewer serious outcomes W2W3 |
In adults, amphetamines (SMD −0.79), methylphenidate (−0.49), bupropion and atomoxetine beat placebo on clinician-rated symptoms at about 12 weeks; head-to-head, amphetamines were more efficacious than methylphenidate and atomoxetine; tolerability was lower than placebo for amphetamines and methylphenidate.
R2Adults stable on lisdexamfetamine for at least six months, randomised to continue or switch to placebo, relapsed at 8.9% versus 75.0% over six weeks, mostly within two weeks.
R1Starting medication was associated with lower two-year all-cause mortality (HR 0.79) and unnatural-cause mortality (HR 0.75), but not natural-cause mortality.
W2Registry studies cannot fully rule out that people who start treatment differ in ways that also lower risk. Target-trial emulation reduces this, but does not remove it. Short trials measure symptoms; registries measure events. Neither measures the long-term effect of withdrawing an established treatment in adults — that gap is real.
Long-term randomised evidence in adults is limited; the strongest long-term outcome data are observational.