Treatment-specific and shared predictors for response to pharmacotherapies for attention-deficit/hyperactivity disorder (ADHD) among children were found in a study published in the Journal of the American Academy of Child & Adolescent Psychiatry.

Children (N=181) with ADHD aged 7 to 14 years were recruited to participate in this trial conducted by the University of California, Los Angeles. Pretreatment clinical symptoms were evaluated using the ADHD Rating Scale IV (ADHD-RS-IV) and electroencephalography (EEG).

Participants were randomly assigned to receive 5 to 20 mg/day extended-release d-methylphenidate (DMPH) for 4 weeks followed by 4 weeks of placebo (n=69), 1 to 3 mg/d guanfacine (GUAN) for 8 weeks (n=68), or 4 weeks GUAN followed by 4 weeks of GUAN plus DMPH (COMB; n=70). EEG characteristics were evaluated as markers for change in ADHD-RS scores at week 8.

Continue Reading

The DMPH, GUAN, and COMB cohorts comprised 66.7%, 66.2%, and 72.9% boys; aged mean 10.1 (SD, 2.0), 10.1 (SD, 2.1), and 9.9 (SD, 2.2) years; 73.9%, 75.0%, and 58.6% were White; 46%, 56%, and 50% had combined inattentive and hyperactive-impulsive ADHD; 48%, 41%, and 44% had inattentive ADHD; and ADHD-RS scores at baseline were 20.4 (SD, 8.1), 18.7 (SD, 11.2), and 17.9 (SD, 9.8) points, respectively.

Greater improvement in ADHD-RS scores were predicted by baseline oppositional (β, -0.21; P <.01), separation panic (β, -0.23; P <.01), hyperactivity-impulsivity (β, 0.21; P =.02), and harm avoidance (β, -0.17; P =.05) behaviors.

Among the COMB cohort, a greater ADHD-RS score improvement was predicted by EEG beta power (β, 0.30; P <.01), retrieval (β, 0.37; P <.01), and maintenance (β, 0.29; P =.03). For GUAN, the opposite pattern was observed, in which beta power had a negative relationship with ADHD-RS score improvement (β, -0.34; P =.03). No EEG effects were significant for the DMPH cohort.

Treatment response, defined as ≥30% improvement in ADHD-RS score, for the COMB cohort was associated with weaker power decreases during encoding (odds ratio [OR], 13.34; P =.01) and retrieval (OR, 7.75; P =.01). Response to GUAN was associated with stronger power decreases during retrieval (OR, 0.19; P =.04). For DMPH, beta power during encoding predicted treatment response (OR, 0.04; P <.01).

For COMB, a model including both clinical and EEG predictors was the best fit (R2, 0.41; P <.01) compared with the model containing only clinical (R2, 0.21; P =.03) or EEG (R2, 0.27; P <.01) measures alone. Similarly, for GUAN the combined model (R2, 0.34; P <.01) outperformed the EEG (R2, 0.24; P <.01) or clinical (R2, 0.14; P =.18) models alone.

The major limitation of this study was the short duration. Additional study is needed to evaluate long-term effects.

“We report initial evidence that EEG cortical source activity may predict clinical improvements in response to combination treatment and monotherapy in children with ADHD,” the study authors concluded. “The identified midfrontal EEG profiles represent candidate brain biomarkers that, if replicated in future studies, may be used alongside clinical measures to assist in personalized treatment decision making for ADHD pharmacotherapy.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Michelini G, Lenartowicz A, Vera JD, et al. Electrophysiological and clinical predictors of methylphenidate, guanfacine, and combined treatment outcomes in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2022;S0890-8567(22)01229-1. doi:10.1016/j.jaac.2022.08.001

This article originally appeared on Psychiatry Advisor