Nonstimulants May Be an Appropriate Alternative to Stimulants for Treating ADHD

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Nonstimulants may be an appropriate alternative in cases in which co-occurring conditions might prevent the administration of stimulants.

Both stimulant and nonstimulant therapies were satisfactory treatments of attention-deficit/hyperactivity disorder (ADHD) in youth, according to the findings of a study published in the Journal of Child and Adolescent Psychopharmacology.

The meta-analysis comprised 15 randomized controlled trials identified via several databases, including 4648 children (mean age 11.06) diagnosed with attention-deficit/hyperactivity disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. These trials investigated either stimulant or nonstimulant medications and reported Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV scores as the primary outcome. Some also reported treatment-emergent adverse effects as a secondary outcome. All trials lasted ≥3 weeks with a mean duration of 5.28 weeks.

Overall, both treatments reduced rating scale scores with a standardized mean difference of −0.70 (95% CI −0.85 to −0.55), or −0.83 (95% CI, −1.11 to −0.54) for stimulants and −0.58 (95% CI, −0.69 to −0.46) for nonstimulants as determined by subgroup analyses.

As expected, each group exhibited varying treatment-emergent adverse effects. Participants taking stimulants were more likely to report decreased appetite (28.6% vs 14.2%), while participants taking nonstimulants were more likely to report drowsiness (34.1% vs 4.4%). However, the frequency of adverse effects did not vary between groups and no significant change in heart rate was noted for either medication.

A limitation of the meta-analysis was its fairly small size and the use of studies with uniform outcome measures; it is possible that heterogeneity was higher than reported. It was also unknown whether the participants in these trials were taking any medication in addition to stimulants or nonstimulants.

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Previous research has suggested that stimulants are significantly more effective than nonstimulants in treating childhood attention-deficit/hyperactivity disorder. While the findings of the meta-analysis corroborated that stimulants may have a greater overall effect size, the difference was not statistically notable, and suggested that nonstimulants may be an appropriate alternative in cases in which co-occurring conditions might prevent the administration of stimulants.


Cerrillo-Urbina A, García-Hermoso A, Pardo-Guijarro M, et al.  The effects of long-acting stimulant and nonstimulant medications in children and adolescents with attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials [published online June 13, 2018]. J Child Adolesc Psychopharmacol. doi:10.1089/cap.2017.0151