Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.

Objective: Trigeminal nerve stimulation (TNS), a minimal risk, non-invasive neuromodulation method, has showed potential benefits for attention-deficit/hyperactivity disorder (ADHD) in an unblinded open study. This blinded sham-controlled trial was conducted to assess efficacy and safety of TNS for ADHD, as well as potential changes in brain spectral power using resting-state quantitative electroencephalography (qEEG). Method: 62 children aged 8-12 years, with full-scale IQ ≥ 85 and KSADS-diagnosed ADHD, were randomized to four weeks nightly treatment with active or sham TNS, followed by one-week without intervention. Assessments included weekly clinician-administered ADHD-Rating Scales (ADHD-RS) and Clinical Global Impression (CGI) scales, and qEEG at baseline and week 4. Results: ADHD-RS totals showed significant group-by-time interactions (F = 8.12, df = 1/228, p = .005); week 4 Cohen's d = .5. CGI-Improvement also favored active treatment (Chisq = 8.75, df = 1/168, p = .003); number-needed-to-treat (NNT) = 3. Resting-state qEEG showed increased spectral power in right frontal and frontal midline frequency bands with active TNS. Neither group had clinically meaningful adverse events. Conclusion: This study demonstrates TNS efficacy for ADHD in a blinded sham-controlled trial, with estimated treatment effect size similar to non-stimulants. TNS is well-tolerated and

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Objective Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and alpha2A agonism may yield enhanced clinical and cognitive responses. The study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH), with guanfacine (GUAN), an alpha2A receptor agonist, would be clinically superior to either monotherapy, and have equal tolerability. Method An 8-week, double-blind, three-arm comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or the combination (COMB) with fixed-flexible dosing. Outcome measures were the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) Scale. Adverse events and safety measures were obtained. Results 207 participants were randomized and received drug. Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total (p = .0001) and inattentive symptoms (p = .0001). COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies (DMPH: p = .05; f2 = .02; and GUAN: p = .02; f2 = .02), and was associated with a greater positive response rate by CGI-I (p = .01). No serious cardiovascular events occurred. Sedation, somnolence, lethargy, and fatigue were greater in both guanfacine groups. All treatments were well tolerated. Conclusion COMB showed consistent evidence of clinical benefits over monotherapies, possibly reflecting advantages of greater combined dopaminergic and alpha2A agonism. Adverse events were generally mild to moderate, and COMB treatment showed no differences in safety or tolerability.