Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled crossover trial
PubMed 30381248 · doi:10.1016/j.jsbmb.2018.10.016
What was done
In a randomized, double-blind, placebo-controlled crossover trial, 24 healthy subjects received single equimolar doses of d-amphetamine (40 mg), lisdexamfetamine (100 mg), and placebo. Plasma concentrations of d-amphetamine and circulating steroids (including ACTH, glucocorticoids, androgens, and mineralocorticoids) were measured over 24 hours post-dose.
What was found
Lisdexamfetamine produced a delayed onset and delayed peak plasma concentration of d-amphetamine compared to d-amphetamine administration, but maximal concentrations and total exposure (AUC) were similar. Both lisdexamfetamine and d-amphetamine significantly increased plasma levels of ACTH, glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol), androgens (DHEA, DHEA-S, and androstenedione), and progesterone (men only) compared with placebo. Maximal steroid concentrations and total steroid AUCs did not differ between the two active treatments, though lisdexamfetamine shifted curves to later time points. Neither drug altered levels of aldosterone, 11-deoxycorticosterone, or testosterone. The abstract reported no numerical values or exact p-values.
Why it matters
This study shows that the prodrug lisdexamfetamine stimulates the hypothalamic-pituitary-adrenal axis and raises circulating adrenal steroids to the same overall degree as immediate-release d-amphetamine, differing mainly in a delayed time course.
Limits
The sample size was small (24 healthy volunteers rather than clinical ADHD patients). Only acute, single-dose exposures were evaluated, which does not reflect chronic therapeutic use. Exact numerical steroid levels and variance metrics were not provided in the abstract.
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