First-line ADHD Meds Differ for Children, Adults
By Marilynn Larkin
NEW YORK—For short-term treatment of attention deficit hyperactivity disorder (ADHD), methylphenidate is the first-line drug of choice for children, and amphetamines are best for adults, according to authors of a network meta-analysis.
"There are now a number of different drugs available for the treatment of ADHD symptoms and . . . (our) network meta-analysis will help guide clinicians in the selection of first-line treatment," Dr. Andrea Cipriani of the University of Oxford told Reuters Health.
"An important new finding is the difference between children and young people on the one hand, and adults on the other," he said by email. "In children, while amphetamines were marginally more efficacious than methylphenidate, (they) were less well tolerated, giving rise to the preference for methylphenidate as first-line in this age group when both parameters are considered. This was not the case for adults."
"The difference in tolerability of amphetamines across age groups had not been appreciated previously," he noted. "The reasons for this difference are not presently known."
Dr. Cipriani and colleagues studied outcomes of 133 double-blind, randomized controlled trials including more than 14,000 children and adolescents and 10,000 adults. The trials compared amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate and modafinil with each other or placebo.
As reported online August 7 in The Lancet Psychiatry, the 12-week efficacy analysis was based on 10,068 children and adolescents and 8,131 adults; the tolerability analysis was based on 11,018 children and adolescents and 5,362 adults.
For physician-rated ADHD core symptoms (hyperactivity, impulsivity and inattention) in children and adolescents, all included drugs were superior to placebo (e.g., standardized mean difference: -1.02, for amphetamines; -0.78, for methylphenidate; -0.56 for atomoxetine).
By contrast, for teacher-rated comparisons, only methylphenidate (SMD -0.82) and modafinil (-0.76) were more effective than placebo. There were no data on teacher ratings for amphetamines or clonidine.
For clinician-rated symptoms in adults, amphetamines (SMD -0.79), methylphenidate (-0.49), bupropion (-0.46) and atomoxetine (-0.45) were better than placebo. No data were available for guanfacine and clonidine.
With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio, 2.30) and adults (OR, 3.26). Guanfacine was inferior to placebo only in children and adolescents (OR, 2.64). Atomoxetine (OR, 2.33), methylphenidate (OR, 2.39) and modafinil (OR, 4.01) were less well tolerated than placebo only in adults.
In head-to-head comparisons, only differences in clinician-rated efficacy were found, and favored amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs -0.46 to -0.24) and adults (-0.94 to -0.29).
Amphetamines, methylphenidate, atomoxetine, and modafinil caused weight loss in children, adolescents and adults. Amphetamines and atomoxetine increased blood pressure in children and adolescents, as did methylphenidate in adults.
"Our results highlight the importance of monitoring both weight and blood pressure across the age span," Dr. Cipriani said.
Efficacy and tolerability at 26 and 52 weeks could not be assessed because of insufficient data. Further, there was insufficient evidence to confirm wither lisdexamfetamine, which is currently recommended by UK guidelines for adults with ADHD, was more effective or better tolerated than other amphetamines.
"New research should be funded urgently to assess long-term effects of these drugs," the authors conclude.
"Although methylphenidate and amphetamine were selected as the best first-line treatment for children and adults, respectively, it is important to note that alternatives, including atomoxetine and guanfacine in children, can be effective and can be a treatment choice," Dr. Cipriani said.
"Pharmacological treatments are more effective in tackling the core symptoms of ADHD, while non-pharmacological treatments are used for oppositional behavior, defiant behaviors or emotional distress," he added. "We focused on medications, but this does not mean that non-pharmacological treatment is less important; the two approaches should be considered at the same time and offered to patients, carers and family for an informed shared-decision process."
Dr. Mark Stein of the University of Washington in Seattle, coauthor of a related editorial, commented by email, "Despite the long history of ADHD and ADHD medication treatment, this is just a start, as the majority of individuals with ADHD need a more thorough treatment plan that may involve medication as well as behavioral therapy and other interventions, depending on each patient's presentation and response to previous treatments."
"Monotherapy for a short period of time is seldom adequate for a complex, heterogeneous condition such as ADHD that varies through the lifespan," he said. "For younger children, we recommend beginning with behavioral therapy, except in severe cases."
"Treatment should involve more than medication, but include psychoeducation and address the skill and performance deficits displayed by individuals with ADHD that contribute to their difficulties in everyday life," Dr. Stein concluded.
SOURCE: https://bit.ly/2OGRW59 and https://bit.ly/2MMKuod
Lancet Psychiatry 2018.
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