Background Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) (Azstarys®) is an FDA-approved treatment for ADHD in patients aged 6 years and older. With its prodrug formulation, SDX/d-MPH provides rapid and sustained efficacy. Methods This study compared the tolerability of SDX/d-MPH with other approved extended-release (ER) stimulant medications by evaluating patient-reported side effects in a real-world sample of patients with ADHD prescribed SDX/d-MPH, lisdexamfetamine (LDX), amphetamine ER (AMP), or methylphenidate ER (MPH). Digital survey responses from 1,395 patients (age: M ± SD = 32.5 ± 14.1 years, range = 7–78 years) treated for ADHD at a single large outpatient psychiatric practice were analyzed. Patients completed the ADHD Symptom and Side Effect Tracking (ASSET) scale in digital pre-visit surveys. Analyses focused on a filtered subset of 697 surveys reflecting early treatment (≤90 days) and ER stimulant monotherapy. Multinomial logistic regressions were conducted to examine associations between side effect frequency and prescription type. Differences in side effect frequency across prescription types were examined using one-way ANOVA with Tukey-adjusted comparisons and ANCOVA controlling for age and time since treatment initiation. To account for within-patient clustering, a MANCOVA including patient as a fixed effect was conducted as a robustness check. Results Prescription type was associated with all four side effects (all p 0.05). Logistic regression analyses indicated that insomnia ( p = 0.006), end-of-dose crash ( p = 0.046), and return of symptoms ( p = 0.036) were associated with prescription type, although effect sizes were modest. Pairwise comparisons showed that patients taking SDX/d-MPH reported lower frequency of insomnia compared to AMP ER ( p = 0.024) and LDX ( p = 0.006), and lower frequency of end-of-dose crash compared to AMP ER ( p = 0.046). MANCOVA found significant differences between prescription types were observed for insomnia ( p = 0.036) and end-of-dose crash ( p = 0.021), but not for poor appetite or return of symptoms. Conclusion In this single-center retrospective analysis of patient surveys, patients with ADHD taking SDX/d-MPH reported reduced frequency of insomnia compared to AMP ER and LDX, and lower frequency of end-of-dose crash compared to AMP ER. This real-world tolerability analysis highlights the importance of considering side effects in ADHD treatment.
YOUNG et al. (Thu,) studied this question.