Characterizing the Placebo Response in Adults with ADHD

Rationale: The placebo response in psychiatry in general and in ADHD in particular is of major importance. In recent years, several phase-III clinical trials have failed to show efficacy, exposing high placebo response rates.
Objective: To characterize the placebo response to non-stimulants in adults with ADHD.
Methods: A retrospective data analysis of the placebo arm of a 6-week multicenter double-blind randomized clinical trial of metadoxine XR 1,400 mg, including 125 adults (aged 18-55 years) with ADHD. Subjects with medical or major psychiatric comorbidities or psychotropic medications were excluded. Subjects were evaluated using the Conners` Adult ADHD Rating Scale (CAARS) and Adult ADHD Self-Report Scale (ASRS), the golden-standard measures in clinical trials according to the FDA. We used repeated-measures one-way ANOVA and logistic regression for data analysis.
Results: The metadoxine placebo elicited a significant improvement in CAARS and ASRS values over time (F(2.6, 318.9)=69.2, p<.00001, partial η²=0.34; and F(2.4, 300.7)=43.9, p<.00001, partial η²=0.26, respectively). By week 6, mean CAARS scores improved from 37.5 ± 8.0 at baseline to 27.1 ± 12.0 and ASRS scores from 46.5 ± 10.6 to 35.8 ± 13.7. Body Mass Index (BMI)>29.0 predicted a significant placebo response as 40% improvement in CAARS at week 6 (OR=2.4, p=.03), but vital signs did not. Nausea as a nocebo effect was marginally more prevalent in placebo responders (χ²=2.9, p=.089). Further results will be presented at the meeting.
Conclusions: Non-stimulant placebos can exert powerful clinical responses in ADHD. Significant overweight may help predict placebo responses in future clinical trials.