Investigators at Massachusetts General Hospital, Boston, MA, performed a multicenter, 9-week, double-blind, placebo-controlled, dose-optimization study of guanfacine extended release (GXR, <4 mg/d) adjunctive to a long-acting psychostimulant for ADHD continued in 461 subjects. Patients were randomized to receive GXR in the morning (GXR AM), GXR in the evening (GXR PM), or placebo.
GXR treatment groups showed significantly greater improvement from baseline compared with placebo plus psychostimulant. Small mean decreases in pulse, systolic, and diastolic blood pressure were observed in GXR treatment groups. Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement and generated no new safety signals. 
COMMENTARY. A similar randomized, double-blind trial of guanfacine extended release (Intuniv) administered either in the morning ((n = 107) or evening (n= 114) was associated with significant improvements in ADHD symptoms. Once-daily GXR monotherapy is effective, administered AM or PM . The rapid-release guanfacine (Tenex) is often prescribed as an alternative to Intuniv because of cost and insurance denial. Tenex is often effective in the hyperactive/ADHD younger child with sleep disorder or tics, but drowsiness during the day may lessen the ability to focus in school. The effect of Intuniv on school performance and grades requires further study.