Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

Abstract

David R Coghill,1 Tobias Banaschewski,2 Michel Lecendreux,3 César Soutullo,4 Alessandro Zuddas,5 Ben Adeyi,6 Shaw Sorooshian7 1Division of Neuroscience, University of Dundee, Dundee, UK; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 3Paediatric Sleep Centre and National Reference Centre for Orphan Diseases: Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Robert-Debré University Hospital, Paris, France; 4Child and Adolescent Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra Clinic, Pamplona, Spain; 5Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; 6Shire, Wayne, PA, USA; 7Shire, Eysins, Switzerland Background: Following the approval of lisdexamfetamine dimesylate (LDX) in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories. Methods: This was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH). OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I) scores. Results: The difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval) was similar between the overall study population (n=317; LDX, -18.6 [-21.5, -15.7]; OROS- MPH, -13.0 [-15.9, -10.2]) and treatment-naïve individuals (n=147; LDX, -15.1 [-19.4, -10.9]; OROS-MPH, -12.7 [-16.8, -8.5]) or patients previously treated with any ADHD medication (n=170; LDX, -21.5 [-25.5, -17.6]; OROS-MPH, -14.2 [-18.1, -10.3]). In addition, similar proportions of patients receiving active treatment were categorized as improved based on CGI-I score (CGI-I of 1 or 2) in the overall study population and among treatment-naïve individuals or patients previously treated with any ADHD medication. Conclusion: In these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication. Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine dimesylate, methylphenidate, central nervous system stimulants