TY - JOUR
T1 - A Double-blind Placebo Controlled Study of Desipramine in the Treatment of ADD
T2 - II. Serum Drug Levels and Cardiovascular Findings
AU - BIEDERMAN, JOSEPH
AU - BALDESSARINI, ROSS J.
AU - WRIGHT, VIRGINIA
AU - KNEE, DEBRA
AU - HARMATZ, JEROLD S.
AU - GOLDBLATT, ALLAN
PY - 1989
Y1 - 1989
N2 - In a 6-week study of children and adolescents with attention deficit disorder with hyperactivity (ADDH) in which desipramine (DMI) was highly effective and well tolerated, the mean maximal daily oral dose in the DMI-treated patients (N = 31) was 4.6 ± 0.2 mg/kg. Additional data were obtained for 27 placebo nonresponders given DMI openly for 6 additional weeks following a nearly identical protocol and mean daily doses (total N = 58). Individual serum drug concentration varied widely at a given dose. The overall median serum DMI level was 152 ng/ml and in 6 of 56 cases with assayed serum (DMI), the level exceeded 500 ng/ml. Serum tended to be higher with older age and greater clinical improvement. Only small, clinically unimportant but statistically significant increases in diastolic blood pressure, heart rate, and electrocardiographic conduction parameters occurred. DMI-treated patients showed higher incidence during DMI treatment of sinus tachycardia and ECG evidence of intraventricular conduction defect (IVCD) of the right bundle branch block type, with two of these patients developing complete IVCD. Increases in ventricular rate and in ECG conduction parameters, as well as the incidence of IVCD, were higher in patients attaining serum levels of DMI above the median. These findings suggest that, although treatment with DMI at daily doses above 3.5 mg/kg may be needed in some cases of childhood ADDH, such doses require caution and monitoring of serum drug levels and ECG when they are used in the pediatric population.
AB - In a 6-week study of children and adolescents with attention deficit disorder with hyperactivity (ADDH) in which desipramine (DMI) was highly effective and well tolerated, the mean maximal daily oral dose in the DMI-treated patients (N = 31) was 4.6 ± 0.2 mg/kg. Additional data were obtained for 27 placebo nonresponders given DMI openly for 6 additional weeks following a nearly identical protocol and mean daily doses (total N = 58). Individual serum drug concentration varied widely at a given dose. The overall median serum DMI level was 152 ng/ml and in 6 of 56 cases with assayed serum (DMI), the level exceeded 500 ng/ml. Serum tended to be higher with older age and greater clinical improvement. Only small, clinically unimportant but statistically significant increases in diastolic blood pressure, heart rate, and electrocardiographic conduction parameters occurred. DMI-treated patients showed higher incidence during DMI treatment of sinus tachycardia and ECG evidence of intraventricular conduction defect (IVCD) of the right bundle branch block type, with two of these patients developing complete IVCD. Increases in ventricular rate and in ECG conduction parameters, as well as the incidence of IVCD, were higher in patients attaining serum levels of DMI above the median. These findings suggest that, although treatment with DMI at daily doses above 3.5 mg/kg may be needed in some cases of childhood ADDH, such doses require caution and monitoring of serum drug levels and ECG when they are used in the pediatric population.
KW - attention deficit disorder
KW - cardiovascular effects
KW - desipramine
KW - serum levels
UR - http://www.scopus.com/inward/record.url?scp=0024804130&partnerID=8YFLogxK
U2 - 10.1097/00004583-198911000-00015
DO - 10.1097/00004583-198911000-00015
M3 - Article
C2 - 2808261
AN - SCOPUS:0024804130
SN - 0890-8567
VL - 28
SP - 903
EP - 911
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 6
ER -