Prediction of Placebo Response in 2 Clinical Trials of Lisdexamfetamine Dimesylate for the Treatment of ADHD
J Clin Psychiatry 2011;72(10):1366-1375
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Objective: To search for predictors of placebo response in clinical trials of lisdexamfetamine dimesylate for the treatment of DSM-IV-TR–defined attention-deficit/hyperactivity disorder (ADHD) in children and adults.
Method: We used data from 2 clinical trials: (1) a 4-week, phase 3, multicenter, randomized, double-blind, forced-dose, parallel-group study of children aged 6 to 12 years with ADHD (n = 290) and (2) a 4-week, randomized, double-blind, placebo-controlled, parallel-group, forced-dose titration study in adult subjects, aged 18–55 years with ADHD (n = 420). Response and remission were defined using the ADHD Rating Scale-IV and the Clinical Global Impressions-Improvement scale.
Results: Symptom remission was inversely correlated with baseline severity in both children and adults (P < .001), with less robust effects seen for response. The time to response and remission was delayed in adult subjects prescribed placebo versus lisdexamfetamine dimesylate, while response time in children was also significantly slower with placebo versus lisdexamfetamine dimesylate (P < .01). We found little evidence that demographic factors, prior pharmacotherapy, the emergence of adverse events during the trial, or changes in ADHD symptoms from the screening to baseline assessments predicted placebo response. Certain comorbid medical symptoms reduced the response and remission rates to placebo in children (P < .001) and adults (P < .001).
Conclusions: In both children and adults, baseline symptom severity was the most consistent predictor of remission with placebo while the temporal profile of response reliably differentiated placebo from medication responders. Placebo effects are most likely to be minimized in shorter trials enrolling more severely impaired subjects. The impact of medical and psychiatric comorbidities on placebo response merits further investigation.
Trial Registration: clinicaltrials.gov identifiers NCT00556296 and NCT00334880
J Clin Psychiatry
Submitted: January 13, 2010; accepted April 1, 2010.
Online ahead of print: February 8, 2011 (doi:10.4088/JCP.10m05979pur).
Corresponding author: Stephen V. Faraone, PhD, SUNY Upstate Medical University, 750 East Adams St, Syracuse, NY 13210 (firstname.lastname@example.org).