Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.
OBJECTIVE
To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD).


METHODS
In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs.


RESULTS
There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks.


CONCLUSIONS
Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.
Daviss
W Burleson
WB
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Patel
Nick C
NC
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Robb
Adelaide S
AS
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
McDERMOTT
Michael P
MP
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Bukstein
Oscar G
OG
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Pelham
William E
WE
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Palumbo
Donna
D
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Harris
Peter
P
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
Sallee
Floyd R
FR
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.. Electronic address: floyd.sallee@uc.edu.
Dr. Daviss is affiliated with University of Texas Health Science Center at San Antonio; Dr. Bukstein is with the University of Pittsburgh; Drs. Patel and Sallee are with the University of Cincinnati; Drs. McDermott, Palumbo, and Harris are with the University of Rochester; Dr. Pelham is with State University of New York at Buffalo; and Dr. Robb is with George Washington University School of Medicine and Children's National Medical Center.
D000316:Adrenergic alpha-Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D001919:Bradycardia / Q000139:chemically induced; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D003000:Clonidine / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use; D010552:Personality Assessment; D012894:Sleep Stages / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced
D000316:Adrenergic alpha-Agonists; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003000:Clonidine