Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity

Abstract

Objective:

To examine the impact of baseline severity on lisdexamfetamine dimesylate (LDX) efficacy in a long-term study of adults with attention-deficit/hyperactivity disorder (ADHD).

Research design and methods:

Adults from a 4-week, placebo-controlled, forced dose-escalation study with LDX (30–70 mg/day) or placebo were enrolled in a long-term, open-label dose-optimization study for an additional 12 months. In post hoc analyses, participants were stratified by baseline severity (from the prior short-term study) with Clinical Global Impressions-Severity (CGI-S) scores of 4 (moderately), 5 (markedly), or ≥6 (severely/extremely ill). ADHD-Rating Scale IV (ADHD-RS-IV) with adult prompts (primary) and CGI-Improvement (CGI-I) were used to assess effectiveness. Clinical response was defined as a ≥30% decrease in ADHD-RS-IV from baseline and a CGI-I of 1 or 2; symptomatic remission was defined as ADHD-RS-IV ≤18. Treatment-emergent adverse events (TEAEs) were monitored.

Results:

Participants had baseline CGI-S scores of 4 (n = 114), 5 (n = 188), or ≥6 (n = 43). At endpoint, mean (SD) change from baseline in ADHD-RS-IV was greater (p < 0.0001) for participants with CGI-S = 5 (−26.4 [11.77]) and ≥6 (−32.3 [9.81]) than for participants with CGI-S = 4 (−19.5 [9.97]). At endpoint, 81.6%, 84.6%, and 88.4% of participants were very much/much improved (CGI-I of 1 or 2) in CGI-S categories of 4, 5, and ≥6, respectively. Clinical response criteria were met by 78.9%, 83.5%, and 88.4% and symptomatic remission criteria by 64.0%, 65.4%, and 72.1% of participants with CGI-S = 4, 5, and ≥6, respectively. The most frequently reported TEAEs with participant incidence ≥10% for any LDX dose were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%).

Conclusions:

Some aspects of these analyses (e.g., open-label design without placebo control, inclusion and exclusion criteria of the demographic profile of participants, and the post hoc nature of the statistical analysis) limit interpretation. However, long-term LDX treatment demonstrated increased degree of symptom improvement with greater baseline symptom severity. Rates of clinical response and symptomatic remission tended to be greater for those with greater baseline severity. LDX demonstrated a safety profile consistent with long-acting stimulant use.

Key words::

• ADHD-RS-IV
• Adult
• Attention-deficit/hyperactivity disorder (ADHD)
• Clinical Global Impressions
• Lisdexamfetamine dimesylate (LDX)
• Severity

Transparency

Declaration of funding

Clinical research and editorial/writing assistance was funded by Shire Development Inc.

Declaration of financial/other relationships

Dr Ginsberg receives or has received research grant support from Abbott Laboratories, Alkermes, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, McNeil, Neurocrine Biosciences, Neuropharm, New River, Novartis, Organon, Ortho-McNeil, Otsuka, Pamlab, Pfizer, sanofi-aventis, Seaside Therapeutics, Sepracor, Shire, Takeda, UCB Pharma, Validus, and Wyeth; served on a speaker's bureau for Alkermes, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Jazz, JDS Pharmaceuticals, McNeil, Merck, Novartis, Noven, Organon, Pamlab, Pfizer, sanofi-aventis, Schwarz, Sepracor, Shire, Takeda, UCB Pharma, Validus, and Wyeth; and is a consultant for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Labopharm, McNeil, Novartis, Ortho-McNeil, Pfizer, sanofi-aventis, Sepracor, Shire, Takeda, UCB Pharma, Validus, and Wyeth. Dr Katic receives or has received research grant support from Abbott Laboratories, Alexza, AstraZeneca, Bristol-Myers Squibb, Cephalon, Corcept, Cyberonics, Dainippon Sumitomo, Eli Lilly, Forest, GlaxoSmithKline, Hisamitsu, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, sanofi-aventis, Sepracor, Shire, Takeda, and Wyeth and served on a speaker's bureau for Novartis, Pfizer, and Shire. Mr Adeyi is an employee of Shire and holds stock and/or stock options in Shire. Dr Dirks is an employee of Shire and holds stock and/or stock options from Johnson & Johnson and Shire. Dr Babcock is an employee of Shire and holds stock and/or stock options in Shire. Dr Lasser is an employee of Shire and holds stock and/or stock options in Shire. Dr Scheckner is an employee of Shire and holds stock and/or stock options in Shire. Dr Adler receives or has received research grant support from Bristol-Myers Squibb, Eli Lilly, National Institute on Drug Abuse, Ortho-McNeil/Janssen/Johnson & Johnson, Pfizer, and Shire. He is or has been a speaker for Ortho-McNeil/Janssen/Johnson & Johnson and Shire. He is or has been on the advisory board and consulted for AstraZeneca, EPI-Q, Eli Lilly, i3 Research, INC Research, Major League Baseball, Mindsite, Organon, Ortho-McNeil/Janssen/Johnson & Johnson, Otsuka, United BioSource, and Shire. In the prior year, Dr Adler received grant/research support, or consulted with, or served on an advisory board or a speaker's bureau for Abbott Laboratories, Bristol-Myers Squibb, Cephalon, Cortex, Eli Lilly, Major League Baseball, Merck, Mindsite, National Institute on Drug Abuse, New River, Novartis, Organon, Ortho-McNeil/Janssen/Johnson & Johnson, Pfizer, PsychoGenics, sanofi-aventis, and Shire. He received royalty payments from New York University (as inventor) for licensing of adult ADHD scales and training materials.

Acknowledgments

Clinical research was funded by Shire Development Inc. Under the direction of the authors, Huda Ismail Abdullah, PhD, and Michael Pucci, PhD, employees of Ogilvy CommonHealth Scientific Communications (OCHSC), provided writing assistance for this publication. Editorial assistance in the form of proofreading, copy editing, and fact checking was also provided by OCHSC. Although the sponsor was involved in the design, collection, analysis, interpretation, and fact checking of information, the content of this manuscript, the ultimate interpretation, and the decision to submit it for publication in Current Medical Research and Opinion were made by the authors independently.