Double-Blind Placebo-Controlled Randomized Clinical Trial of Neurofeedback for Attention-Deficit/Hyperactivity Disorder With 13-Month Follow-up

Abstract

Objective: To determine whether theta/beta-ratio (TBR) electroencephalographic biofeedback (neurofeedback [NF]) has a specific effect on attention-deficit/hyperactivity disorder (ADHD) beyond nonspecific benefit.

Method: In a 2-site double-blind randomized clinical trial, 144 children aged 7 to 10 years with rigorously diagnosed moderate/severe ADHD and theta/beta-ratio (TBR) ≥4.5 were randomized 3:2 to deliberate TBR downtraining versus a control of equal duration, intensity, and appearance. Two early dropouts left 142 children for modified intent-to-treat analysis. The control used prerecorded electroencephalograms with the participant's artifacts superimposed. Treatment was programmed via Internet by an off-site statistician-guided co-investigator. Fidelity was 98.7% by trainers/therapists and 93.2% by NF expert monitor. The primary outcome was parent- and teacher-rated inattention; analysis was mixed-effects regression. Because the expense and effort of NF can be justified only by enduring benefit, follow-ups were integrated.

Results: Blinding was excellent. Although both groups showed significant improvement (p < .001, d = 1.5) in parent/teacher-rated inattention from baseline to treatment end and 13-month follow-up, NF was not significantly superior to the control condition at either time point on this primary outcome (d = 0.01, p = .965 at treatment end; d = 0.23, p = .412 at 13-month follow-up). Responders (Clinical Global Impression-Improvement [CGI-I] = 1-2) were 61% of NF and 54% of controls (p = .36). Adverse events were distributed proportionally between treatments. The 13-month follow-up found nonsignificant improvement from treatment end for NF (d = 0.1), with mild deterioration for controls (d = -0.07). NF required significantly less medication at follow-up (p = .012).

Conclusion: This study does not support a specific effect of deliberate TBR NF at either treatment end or 13-month follow-up. Participants will be reassessed at 25-month follow-up.

Clinical trial registration information: Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD; https://clinicaltrials.gov/; NCT02251743.

Keywords: ADHD; attention-deficit; clinical trials; double-blind; neurofeedback.

Figure 1:. CONSORT Chart

Note: A total of 144 eligible participants were randomized to receive Neurofeedback treatment or Placebo in a 3:2 ratio. Two participants (one from each treatment group) withdrew consent at sessions 3 and 9 for logistical reasons without any assessment of outcomes after baseline. Thus 142 participants were included in the primary analysis (modified ITT population): 58 received control treatment (41%) and 84 active NF; 28 had 19 sessions and exited treatment per protocol; 10 had 20–37 sessions; and 104 completed all sessions. All 142 participants were expected to participate in the evaluation at treatment end (session 40) and all Follow-ups, and most did (128 at 13 month follow-up, 90% retention).

Figure 2:. Primary Outcome

Note: Composite average of parent- and teacher-rated DSM-5 inattention from baseline to 13-month follow-up on a 0–3 metric. ES = effect size, Cohen’s d; F/U – follow-up; NF = neurofeedback; Trt = Treatment. ^a Estimated using the mixed effects model ^b Baseline standard deviation ^c p-values of the comparisons within and between treatment groups are based on the mixed effects models.