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.