Among children and adolescents who had completed prolonged lisdexamfetamine treatment, continuing treatment better maintained several parent-rated functional and quality-of-life outcomes than switching to placebo. This withdrawal design answers a maintenance question in selected continuing participants.
Banaschewski and colleagues reported secondary outcomes from a study involving an open-label treatment period of at least 26 weeks followed by six weeks of double-blind randomized withdrawal. Participants aged 6–17 years either continued an optimized lisdexamfetamine dose or switched to placebo.
The open-label full analysis set included 262 participants; the randomized-withdrawal full analysis set included 153, divided between 76 continuing active treatment and 77 receiving placebo. The randomized sample therefore represented people who had remained in treatment through the preceding phase, rather than all newly presenting patients with ADHD.
Parents completed a child health-related quality-of-life questionnaire and the Weiss Functional Impairment Rating Scale–Parent Report. During withdrawal, scores generally deteriorated after switching to placebo and remained more stable with continued lisdexamfetamine.
Significant between-group findings included the quality-of-life domains Risk Avoidance, Achievement and Satisfaction. Functional-impairment comparisons favored continued treatment for Family, Learning and School, Risky Activities and the total score. These were secondary analyses with nominal p values that were not adjusted for multiple comparisons. Not every domain comparison demonstrated superiority.
Randomized withdrawal strengthens evidence that benefit was maintained by continued treatment in this selected group. It does not provide an unbiased estimate of starting-treatment success among all children, because people who discontinued during the open-label phase were not represented in the randomized comparison.
The six-week withdrawal period and parent-reported outcomes also limit conclusions about long-term educational achievement, injuries or other directly observed events. A questionnaire domain called Risk Avoidance is not a driving-safety test. The study was industry funded, and its rating changes were not linked to measured amphetamine concentrations or an individual impairment cutoff.
Read our analysis of functional ratings and quality of life in adult ADHD.
Health-Related Quality of Life and Functional Outcomes from a Randomized-Withdrawal Study of Long-Term Lisdexamfetamine Dimesylate Treatment in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. doi:10.1007/s40263-014-0193-z.