Tim Wigal1, Laurence Greenhill2, Shirley Chuang1, James McGOUGH1, Benedetto Vitiello1, Anne Skrobala1, James Swanson1, Sharon Wigal1, Howard Abikoff1, Scott Kollins1, James McCRACKEN1, Mark Riddle1, Kelly Posner1, Jaswinder Ghuman1, Mark Davies1, Ben Thorp1, Annamarie Stehli1. 1. Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson. 2. Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.. Electronic address: larrylgreenhill@cs.com.
Abstract
OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment. METHOD:Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5-weekplacebo-controlled, double-blind phase (n=165); a 5-week double-blind, parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean total daily dose at the end of maintenance. Pulse, blood pressure, and the presence of treatment emergent adverse events (AEs), parent and teacher AE ratings, and vital signs were recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported moderate to severe AEs in all study phases after baseline. These included emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts, appetite decrease, and irritability. During titration, decreased appetite (chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=4.0, p<.05) occurred statistically more often on MPH than on placebo. During maintenance, trouble sleeping and appetite loss persisted and other MPH-related AEs decreased. There were transient, one-time pulse and blood pressure elevations in five children. Twenty-one children (11%) discontinued because of drug-attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued treatment because of intolerable MPH AEs. Of the serious AEs reported, one occurred in baseline, two in lead-in, three in titration, one in parallel, and one in maintenance. Only one was possibly related to MPH.
RCT Entities:
OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment. METHOD: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5-week placebo-controlled, double-blind phase (n=165); a 5-week double-blind, parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean total daily dose at the end of maintenance. Pulse, blood pressure, and the presence of treatment emergent adverse events (AEs), parent and teacher AE ratings, and vital signs were recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported moderate to severe AEs in all study phases after baseline. These included emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts, appetite decrease, and irritability. During titration, decreased appetite (chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=4.0, p<.05) occurred statistically more often on MPH than on placebo. During maintenance, trouble sleeping and appetite loss persisted and other MPH-related AEs decreased. There were transient, one-time pulse and blood pressure elevations in five children. Twenty-one children (11%) discontinued because of drug-attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued treatment because of intolerable MPH AEs. Of the serious AEs reported, one occurred in baseline, two in lead-in, three in titration, one in parallel, and one in maintenance. Only one was possibly related to MPH.
Authors: Alexander G Fiks; Michelle E Ross; Stephanie L Mayne; Lihai Song; Weiwei Liu; Jennifer Steffes; Banita McCarn; Robert W Grundmeier; A Russell Localio; Richard Wasserman Journal: Pediatrics Date: 2016-11-15 Impact factor: 7.124