Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD.

Method: The sample comprised 179 participants aged 7 to 14 years old with ADHD (113 boys, 55 girls). Participants were randomized to 1 of 3 blinded conditions: guanfacine (GUAN), d-methylphenidate (DMPH), or the combination (COMB). Electroencephalography (EEG) was performed pre-, mid-, and post-medication titration, with concomitant assessment of behavioral and cognitive functioning.

Results: Analyses of spectral power measures during resting EEG suggested that each medication condition displayed a distinct profile of effects on cortical activity. Significant time effects suggested that GUAN decreased global alpha band (8-12 hertz [Hz]) power, DMPH and COMB increased centro-parietal beta band (13-21 Hz) power, and COMB resulted in decreased theta band (4-7 Hz) power. Relative to other medication groups, COMB was associated with significantly lower theta band power and DMPH with higher beta band power compared with those in the GUAN group. Medication-related changes in theta power were correlated with improvements in behavioral and cognitive functioning.

Conclusion: These data reveal distinct underlying medication-related effects on neural mechanisms. The COMB condition uniquely exhibited an EEG profile that was associated with improved behavioral and cognitive functioning. Clinical trial registration information-Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.

Keywords: children; electroencephalography; medication; stimulants; treatment.

Figure 1. Medication titration schedule

Note: This was an 8-week randomized 1:1:1, comparative parallel-group fixed-flexible dosing study of three treatments. COMB=combination; DMPH= d-methylphenidate; GUAN=guanfacine.

Figure 2. Resting-state electroencephalography spectral power topographs

Note: Relative power for each medication group by frequency band and study visit is shown. There were no significant differences in mean relative spectral power in any frequency band or region across the groups at baseline (all p’s >.2).

Figure 3. Change in electroencephalography spectral power from baseline by medication group

Note: Each figure depicts regional change in relative power in each frequency band from baseline to Week 8 for each medication group. Significant medication group differences are represented by * p<.05, ** p<.01, and significant time effects are represented by ^† p<.05, ^††† p<.01, ^††† p<.001. COMB=combination; DMPH= d-methylphenidate; GUAN=guanfacine.