Predictors of Placebo Response in Adults With Attention-Deficit/Hyperactivity Disorder: Data From 2 Randomized Trials of Osmotic-Release Oral System Methylphenidate

Objective: To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials.

Method: Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral system (OROS) methylphenidate in adults with ADHD defined according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition: the Long-Acting Methylphenidate in Adults with ADHD (LAMDA-I) study (2005-2006, 5 weeks, n = 95) and the LAMDA-II study (2008-2009, 13 weeks, n = 97). The primary efficacy measure was the Conners’ Adult ADHD Rating Scale-observer rated, short version (CAARS:O-SV). Predictors of CAARS:O-SV change were assessed using a random-intercepts model with demographic and disease-related parameters as independent variables. Sensitivity analyses were conducted using the CAARS self-report (CAARS:S-S) and a categorical response criterion (improvement of > 30% in CAARS:O-SV), and in subjects who completed the study.

Results: In LAMDA-I, mean ± SD change in CAARS:O-SV was -7.6 ± 9.9 with placebo and -11.9 ± 10.6 with OROS methylphenidate. Higher baseline CAARS score (P = .007) and lower educational achievement (P = .014) were significantly associated with greater improvement in placebo-treated subjects. In LAMDA-II, mean ± SD change in CAARS:O-SV was -10.4 ± 11.0 and -14.1 ± 10.7 in subjects receiving placebo and OROS methylphenidate, respectively. Variables significantly associated with greater placebo response were higher baseline CAARS:O-SV (P = .019), shorter time since ADHD diagnosis (P < .045), and younger age (P = .014). None of the sensitivity analyses challenged the outcomes.

Conclusions: Possible predictors of placebo response in adults with ADHD include higher severity of ADHD symptoms, younger age, shorter time since diagnosis, and lower educational level.

Trial Registration: ClinicalTrials.gov identifier: NCT00246220 (LAMDA-I) and EudraCT number: 2007-002111-82 (LAMDA-II)

J Clin Psychiatry

© Copyright 2012 Physicians Postgraduate Press, Inc.

Submitted: November 10, 2011; accepted January 26, 2012.

Online ahead of print: June 12, 2012 (doi:10.4088/JCP.11m07528).

Corresponding author: Jan K. Buitelaar, MD, PhD, Department of Cognitive Neuroscience (204), PO Box 9101, 6500 HB Nijmegen, The Netherlands ([email protected]).