An Exploratory Study of Functional Outcome in Stimulant Treatment of ADHD in Adults

The objective of this analysis was to describe the effects of methylphenidate-mediated symptom improvement on functional impairments in adults with ADHD.

This is an exploratory study of self-reported functional impairment on the Weiss Functional Impairment Rating Scale (WFIRS-S) in 351 ADHD adults treated in a forced dose, double blind (DB), randomized, parallel clinical trial of a 16-hr methylphenidate stimulant (PRC-063) for 4 weeks followed by open-label (OL; N = 147) for 6 months.

During the 4-week DB period, there was a statistically significant response to medication versus placebo in the WFIRS-S domain of "work." Forty percent of DB subjects, assigned a random dose of medication, showed functional improvement as defined by the Minimal Clinical Important Differences (MCID) of the WFIRS. At the end of DB, one third of subjects had scores below symptomatic and functional impairment thresholds and two thirds by the end of OL. Although the OL period was uncontrolled, when all subjects had been dose optimized with sufficient time for functional impairment to manifest, all WFIRS functional domains showed clinically-relevant improvements from baseline to end of the 6-month OL (p < .0001). There was a fair-to-moderate correlation between change in symptoms and change in function, but ADHD symptoms were about twice as sensitive to change. The strongest predictor of improvement in function was greater improvement in ADHD symptoms. Younger age predicted greater functional impairment.

This study of the relationship between change in symptoms and functional outcome illustrates that improvement in symptoms may be associated with an almost cotemporaneous improvement in function, that increases over time. Identification of subjects who are symptom responders with residual functional impairment suggests the need for additional intervention to target residual functional difficulty. Further research needs to replicate this methodology using an individually dose optimized design to demonstrate full potential for change and to confirm the domains of functioning in adults with ADHD that are most responsive to stimulant treatment.

https://clinicaltrials.gov/study/NCT02139124.