Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults

Abstract

Objectives:

This analysis assessed the relationship of various cutoff scores of the ADHD Rating Scale IV (ADHD-RS-IV) to levels of improvement in ADHD-related executive function (EF), measured by the Brown ADD Scale for Adults (BADDS), which may provide a measure of clinically meaningful EF improvement after ADHD treatment.

Methods:

Post hoc analysis of a 4-week, open-label, dose-optimization phase in a double-blind, placebo-controlled study of lisdexamfetamine dimesylate (LDX) in adults with ADHD. The BADDS for Adults, a validated, normed, self-report measure of EF in ADHD, provides a qualitative measure to rate treatment progress. The ADHD-RS-IV assesses current symptom status based on DSM-IV criteria. Postbaseline ADHD-RS-IV scores were categorized according to four cutoff criteria of symptom remission: (1) ADHD-RS-IV total score ≤18; (2) ADHD-RS-IV total score ≤10; (3) no ADHD-RS-IV item scored >1; and (4) ADHD-RS-IV total score ≤18 and ≤2 items per subscale with a score of 2. Sensitivity and specificity of criteria for identifying participants with optimal BADDS scores were assessed using receiver operating characteristics (ROC). Safety evaluation included treatment-emergent adverse events (TEAEs).

Results:

At endpoint, 85/127 participants had optimal BADDS scores. Linear ANOVA indicated limited overlap between BADDS and ADHD-RS-IV scores (r ² = 0.20; P < 0.0001). Specificity was similar for criteria 1–4 (0.46, 0.39, 0.39, and 0.42), as were ROC (0.699, 0.776, 0.732, and 0.668). Sensitivity was high for criteria 2 and 3 (0.96, 0.92), lower for criteria 1 and 4 (0.72, 0.75). TEAEs were consistent with those of stimulants.

Conclusion:

Criteria 2 and 3 had satisfactorily high sensitivity, but no criteria had adequate specificity. AUC comparison indicated that criteria 2 and 3 ADHD-RS-IV thresholds may be more accurate assessments of EF normalization as measured by the BADDS. The open-label design, small sample size, and selection criteria limit the applicability of these results to a larger treatment population.

Trial registration: ClinicalTrials.gov identifier: NCT00697515.

Key words::

• ADHD
• BADDS
• Executive function
• Lisdexamfetamine dimesylate
• Receiver operating characteristics
• ROC

Transparency

Declaration of funding

Clinical research was funded by the sponsor, Shire Development Inc.

Declaration of financial/other relationships

T.E.B. is a consultant for Abbott, Eli Lilly, Novartis, and Shire; receives research grants from Eli Lilly; receives royalties for publications from American Psychiatric Press, Psychological Corporation, and Yale University Press. M.B. serves as a speaker for Cephalon, Eli Lilly, McNeil, Novartis, Pfizer, Shire, and Wyeth. M.G. is an employee of Shire and holds stock and/or stock options in Shire. B.A., T.B., B.D. and B.S. are employees of Shire and hold stock and/or stock options in Shire. T.W. is a consultant/has consulted for Eli Lilly, McNeil, Otsuka, and Shire; receives/received honoraria from Eli Lilly, McNeil, Otsuka, and Shire; received research funding from NICHD, NIDA, and NIMH; receives/received research support from Eli Lilly, McNeil, Otsuka, and Shire; serves/served as a speaker for Celltech, Cephalon, Eli Lilly, Janssen, McNeil, Novartis, Otsuka, and Shire.

Acknowledgment

Under the direction of the authors, Karen Dougherty, PhD, and Michael Pucci, PhD, employees of Ogilvy CommonHealth Scientific Communications (OCHSC), provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copy editing, and fact checking was also provided by OCHSC. Gary Chen, PhD, from Shire Development Inc. provided support in programming for statistical analyses. Shire Development Inc. provided funding to OCHSC for support in writing and editing this manuscript. 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.

These data were previously presented at the 163rd Annual Meeting of the American Psychiatric Association, May 22–26, 2010, in New Orleans, LA, USA.

Notes

* Vyvanse is a registered trademark of Shire LLC, Wayne, PA, USA.

* OROS is a registered trademark of the ALZA Corporation.