Formulation Science: Optimizing Stimulant Therapy in ADHD

Gregory Busse, PhD discussed Arynta (liquid lisdexamfetamine) for attention-deficit hyperactive disorder (ADHD) and addressed broader principles of psychiatric formulation development and safety considerations applicable across psychotropic drug classes.

Busse argued that formulation optimization carries clinical significance independent of diagnosis, stating that within any drug class "not all psychotropics even in the same class are equal." He outlined 3 categories of advantage conferred by extended-release formulations: extended therapeutic coverage, ranging from hours to weeks depending on the delivery system; smoother pharmacokinetic profiles that reduce adverse event-associated peaks and efficacy-limiting troughs; and improved adherence through reduced daily dosing burden.¹ He further linked formulation-to-preference alignment with prognostic and health economic benefits, noting that treatment gaps in psychiatric illness worsen long-term outcomes and that undertreated patients incur downstream costs through hospitalizations and risk-taking behaviors including substance use.

Busse returned these principles to the liquid formulation context, reaffirming that "if a patient is averse to taking pills or maybe just prefers a liquid, the availability of a liquid formulation is what the patient may need to have effective treatment that they deserve." He urged clinicians to routinely elicit medication preferences and treatment goals before prescribing, arguing that doing so could prove decisive for treatment success.

On safety, Busse emphasized that lisdexamfetamine carries a class boxed warning for abuse, misuse, and addiction shared by all ADHD stimulants, and noted that a 2023 US Food and Drug Administration drug safety communication standardized warning language across agents regarding diversion risk.² He concluded by reinforcing that clinicians should counsel patients explicitly on these risks relative to benefits, and closed with the principle that "choices, options matter" and that patients deserve individualized pharmacotherapy.

Dr Busse is the director, medical lead of CNS at Azurity Pharmaceuticals.

References

1. Steingard R, Taskiran S, Connor DF, et al. New formulations of stimulants: an update for clinicians. J Child Adolesc Psychopharmacol. 2019;29(5):324-339.

2. Lisdexamfetamine dimesylate (oral route). Mayo Clinic. Accessed May 6, 2026. https://www.mayoclinic.org/drugs-supplements/lisdexamfetamine-dimesylate-oral-route/description/drg-20070888