Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder.
OBJECTIVE
The aim of this study was to evaluate the safety and effectiveness of guanfacine extended release (GXR) administered concomitantly with psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and suboptimal response to a psychostimulant alone.


METHODS
This was a multicenter, open-label, 9-week, dose-escalation study of 75 subjects with ADHD treated with methylphenidate (MPH) or amphetamine (AMP) alone for at least 1 month, yet with suboptimal control of ADHD symptoms. Sixty-three subjects (84.0%) completed the study. Patients received GXR in addition to their psychostimulant. Starting with 1 mg/day, GXR was increased weekly to the highest tolerated dose (1, 2, 3, or 4 mg/day), which was maintained through week 6. GXR was then titrated downward in 1-mg weekly decrements from week 7 through week 9. Psychostimulant treatment regimens were continued until at least week 7.


METHODS
Safety assessments included adverse events (AEs), vital signs, physical examination, clinical laboratory tests, the Pediatric Daytime Sleepiness Scale, and the Pittsburgh Side Effects Rating Scale. Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV), the Conners' Parent Rating Scale-Revised Short Form, Clinical Global Impressions, Parent Global Assessment, and Child Health Questionnaire-Parent Form.


RESULTS
The most common treatment-related AEs were upper abdominal pain (25.3%), fatigue (24.0%), irritability (22.7%), headache (20.0%), and somnolence (18.7%). Most AEs were mild to moderate in severity. Investigator-rated AEs due to blood pressure decreases, heart rate, or electrocardiogram findings were infrequent. Mean changes from baseline (psychostimulant monotherapy just prior to receiving GXR) to end point in ADHD-RS-IV total score were statistically significant overall: -16.1 (p < 0.0001). Significant improvement in both subscales of the ADHD-RS-IV was observed. Improvement of symptoms was observed in a majority of subjects.


CONCLUSIONS
Coadministration of GXR and MPH or AMP was generally safe and associated with statistically significant and clinically meaningful ADHD symptom improvement in children and adolescents.
Spencer
Thomas J
TJ
Clinical and Research Program, Pediatric Psychopharmacology, Harvard Medical School and Massachusetts General Hospital , Boston, Massachusetts, USA. tspencer@partners.org
Greenbaum
Michael
M
Ginsberg
Lawrence D
LD
Murphy
William Rory
WR
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000661:Amphetamine / Q000009:adverse effects / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
D000316:Adrenergic alpha-Agonists; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; D016316:Guanfacine; D000661:Amphetamine