PARIS (FRONTLINE MEDICAL NEWS) – Methylphenidate therapy for attention-deficit/hyperactivity disorder in medication-naive boys significantly improved their sleep quality, timing, and duration in a double-blind randomized trial, Michelle M. Solleveld, MD, reported at the annual congress of the European College of Neuropsychopharmacology.

Moreover, these salutary effects on sleep persisted for at least 1 week after methylphenidate was stopped at the end of the 16-week study, added Dr. Solleveld of the University of Amsterdam.

“Our findings are of high clinical relevance since sleep problems are of major concern to parents and treating physicians when considering pharmacotherapy,” she said.

Indeed, while parents embrace the improvement in behavioral symptoms of ADHD provided by methylphenidate, they often express concern about the possible adverse effects of stimulant medication on their child’s sleep. The new study findings are reassuring on that score.

Sleep difficulties are a major problem in patients with ADHD: They tend to fall asleep later and have more frequent awakenings during the night, which results in decreased total sleep time and sleep efficiency, Dr. Solleveld noted.

Prior studies of methylphenidate’s effects on sleep in pediatric ADHD have yielded mixed results. The negative studies were too brief to provide meaningful results, according to Dr. Solleveld, who said at least 8 weeks of treatment are required in order to evaluate the drug’s effect on sleep problems properly.

She presented a randomized, double-blind, 16-week, placebo-controlled clinical trial involving 50 medication-naive boys with ADHD who were 10-12 years old. Their sleep was assessed via actigraphy measurements taken over 5 consecutive nights, keeping a sleep diary, and answering questionnaires, including the Epworth Sleepiness Scale , at three time points: prior to randomization, 8 weeks into the trial, and finally 1 week after the study ended.

Sleep efficiency – the primary study outcome – showed a strong 5% improvement in the methylphenidate group but was unchanged from baseline in placebo-treated controls. The boys who received methylphenidate fell asleep earlier, had a shorter latency of sleep onset, and slept for longer, compared with their baseline measures or with the sleep results in controls.

The finding that the methylphenidate-induced improvements in sleep persisted for a week after drug clearance is consistent with brain imaging studies carried out by Dr. Solleveld and her coinvestigators. They believe that the effects of stimulant therapy may be age dependent. The investigators previously have shown that adults with ADHD who began treatment with stimulants before age 16 years – when brain development is still ongoing – had lower levels of basal gamma-aminobutyric acid (GABA) and higher GABA response to an oral methylphenidate than did those who began treatment with stimulants after age 23 years. This is thought to be attributable to prolonged reductions in dopamine turnover induced by methylphenidate in the developing brain ( Neuroimage Clin. 2017 Jun 2;15:812-8 ).

The Dutch investigators also have reported that methylphenidate therapy in children with ADHD – but not in affected adults – increased the cerebral blood flow response within the thalamus to a dopamine challenge ( JAMA Psychiatry. 2016 Sep 1;73[9]:955-62 ).

The clinical ramifications of these apparently long-lasting, drug-related alterations in GABA neurotransmission are the subject of ongoing research.

Dr. Solleveld reported having no financial conflicts of interest.


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