Extended-release amphetamine (Dyanavel XR) is associated with reduced immediate-release supplementation in adults with ADHD, regardless of baseline patient variables: a retrospective cohort analysis of medical treatment records
Authors: Young Joel L. , Powell Richard N. , Powell Anna , Welling Lisa L. M. , Granata Lauren , Saal Jaime , Nash Margot 
Published: January 2025

Abstract
Background
Adults with ADHD benefit from treatment with extended-release (ER) formulations that provide symptom control for the entire day. Some patients are advised to supplement their extended-release medication with an immediate-release (IR) medication later in the day if they need to prolong its effects. Given that several FDA-approved ER formulations are available and many individual patient variables may affect efficacy, the purpose of this study was to identify reliable predictors of the tendency for patients to supplement their daily ER medication with an IR medication.

Methods
This retrospective study analyzed data from medical treatment records of adults with ADHD who received at least one ER psychostimulant (amphetamine or methylphenidate preparations) for at least six months between November 2022 and June 2024 (N = 417). Data from their intake evaluations, pre-visit measures of depression, anxiety, and ADHD via validated self-report scales, and post-visit clinician evaluations were compiled from their electronic medical records and the Qualtrics API. The association between Dyanavel XR, IR supplementation, and patient variables were investigated by backward stepwise linear regressions modeled using the variable groupings: (1) side effects reported at baseline, (2) side effects reported after 90 days, and (3) change in depression, anxiety, and ADHD symptoms from baseline to 90 days using assessment scale scores.

Results
Compared to the other amphetamine and methylphenidate ER medications, only Dyanavel XR resulted in lower IR supplementation at 90 days. This relationship held when controlling for baseline IR use. Regardless of whether patients supplemented with an IR, they demonstrated improved ADHD symptoms as measured by the ADHD Symptom and Side Effect Tracking (ASSET) scale after 90 days (d = 0.68 in patients with IR, d = 0.39 in patients without IR). Dyanavel XR was significantly associated with reduced IR supplementation at 90 days compared to the pooled group of patients taking other ER medications (χ2 = 4.320, Nagelkerke R2 = 0.039, p = .038). The CGI-I score at baseline was also significantly associated with supplementation at 90 days (r = .14, p = .010). No other baseline variable was independently associated with IR supplementation. Along with being on Dyanavel XR, improved ADHD and anxiety symptom presentation from the baseline to the 90-day visit predicted reduced IR supplementation (ASSET change: t = 2.377, p = .018; GAD-2 change: t = -2.543, p = .011; Dyanavel XR: t = -2.112, p = .035).

Conclusion
These analyses support Dyanavel XR as a monotherapy for the daily management of ADHD in adults compared with other ER medications. Considering its tendency to reduce IR supplementation and its relationship with improved ADHD and anxiety symptoms, Dyanavel XR may simplify treatment regimens and improve outcomes.

Clinical trial number
Not applicable.