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Slight Symptom Gains but More Dropouts With Unlicensed Stimulant Doses in ADHD
In adults with attention-deficit/hyperactivity disorder (ADHD), stimulant doses escalated beyond US Food and Drug Administration (FDA) recommendations were associated with small, and perhaps nonclinically meaningful, additional improvements in ADHD symptoms. However, the added improvement was accompanied by an increased risk of treatment discontinuation because of adverse events, according to results from a systematic review and meta-analysis published in JAMA Psychiatry.
“In general, practitioners should consider unlicensed doses cautiously,” wrote first author Luis C. Farhat, MD, of the University of São Paulo, Brazil, and study coauthors. “Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose.”
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The systematic review and meta-analysis included 47 double-blind, randomized clinical trials of stimulants against placebo. Researchers used data to evaluate the impact, based on averages, of methylphenidate and amphetamine doses on treatment outcomes in a total 7714 adult participants with ADHD.
“For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts,” the authors wrote.
Unlicensed doses in network meta-analyses were associated with a greater reduction in symptoms compared with licensed methylphenidate doses, with a standardized mean difference of −0.23, according to the study. The additional gain was small, however, and brought with it a 2.02 odds ratio of adverse events dropouts.
For amphetamines, increments in doses were not associated with additional reductions of symptoms compared with licensed doses but were linked with continued additional risk of adverse event dropouts, the study found.
“However,” researchers wrote, “the findings are averages and will not generalize to every patient.”
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