A four-week trial found that two tested doses of extended-release mixed amphetamine salts improved adult ADHD symptom ratings compared with placebo. Its forced-dose design did not determine the best dose for every participant.
Weisler and colleagues randomized 275 adults to placebo or SHP465 mixed amphetamine salts at 12.5 or 37.5 mg daily. The primary endpoint was change in an ADHD rating scale with adult prompts. A clinician global-improvement scale was the key secondary endpoint.
Of the randomized participants, 236 completed the study. The trial therefore should not be described as if everyone assigned treatment completed the full protocol.
At week four, both active doses significantly favored treatment over placebo on ADHD symptom change. The reported placebo-relative differences were −8.1 points for 12.5 mg and −13.4 points for 37.5 mg. Both primary comparisons had p values below 0.001.
The clinician global-improvement measure also favored both active doses. Additional symptom-subscale findings were reported with nominal significance, which should remain distinct from the prespecified primary analysis.
The investigators identified forced-dose titration as different from flexible adjustment in clinical practice. A participant could remain on a dose that was not optimal for balancing benefit and tolerability.
A larger numerical benefit at the higher tested dose therefore does not establish that all patients should receive that dose. Four weeks also cannot characterize all long-term benefits or adverse effects.
ADHD symptom ratings and clinician impressions answer a treatment question. They are not drug-concentration measures, laboratory identification results or validated tests of driving ability.
The study supports efficacy under the selected clinical protocol. It does not imply that every person with amphetamine detected in a specimen is functioning better, or that a therapeutic response can be inferred from a toxicology number alone.
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