Attention deficit hyperactivity disorder in children - Emerging treatments

Serdexmethylphenidate/dexmethylphenidate

Serdexmethylphenidate is a prodrug of dexmethylphenidate, and dexmethylphenidate is the d-threo enantiomer of d,l-methylphenidate, which is the more pharmacologically active enantiomer. The US Food and Drug Administration (FDA) has approved the combination of serdexmethylphenidate (70%) and dexmethylphenidate (30%) for the treatment of attention deficit hyperactivity disorder (ADHD) in children over the age of 6 years. After absorption via the gastrointestinal tract, serdexmethylphenidate is converted to dexmethylphenidate and is designed to gradually release dexmethylphenidate throughout the day. Therefore, the formulation provides rapid symptom control with the dexmethylphenidate, and for an extended duration with the serdexmethylphenidate. The effects have been shown to last for a period of about 12 hours in a phase 3 multi-centre randomised controlled trial (150 children with ADHD aged 6-12 years).[194] There is currently no evidence that its effects or side effects are any different than the existing extended-release formulations, some of which have similar extended-release effects. It is not yet clear if it will be available in a form tolerable for children who cannot swallow pills. Cost will also be a factor since many methylphenidate products now come in generic form.

Viloxazine

Viloxazine, an extended-release non-stimulant drug, is approved by the FDA for the treatment of ADHD in children and young people aged 6-17 years. Viloxazine is a selective noradrenaline inhibitor that has previously been used in the treatment of depression. It can be taken as capsules or sprinkled onto apple sauce. In phase 3 studies, including in total over 1000 children and adolescents with ADHD, viloxazine was shown to significantly improve ADHD symptoms (measured using ADHD Rating Scale-5).[195][196][197]Nasser A, Kosheleff AR, Hull JT, et al. Translating attention-deficit/hyperactivity disorder rating scale-5 and Weiss functional impairment rating scale-parent effectiveness scores into clinical global impressions clinical significance levels in four randomized clinical trials of SPN-812 (viloxazine extended-release) in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2021 Apr;31(3):214-26. However, it may increase suicidal thoughts and actions in some children with ADHD, and monitoring is required during the initial few months of treatment and with any dose changes.

Trigeminal nerve stimulation

In April 2019 the FDA granted marketing authorisation for the Monarch external trigeminal nerve stimulation (eTNS) system®, the first medical device for treating ADHD. It is indicated for patients aged 7-12 years who are not currently taking prescription ADHD medication. It should be used in the home during sleep under the supervision of a carer. The device connects via a wire to a small patch on the patient's forehead. The system delivers low-level electrical stimulation to branches of the trigeminal nerve, which sends signals to areas of the brain thought to be involved in ADHD (i.e., those important in regulating attention, emotion, and behaviour). In a trial, 62 children with moderate to severe ADHD used the device or a placebo device each night for 4 weeks. The eTNS group showed significantly greater improvement in an ADHD symptom score than the placebo group.[198] The National Institute for Health and Care Excellence (NICE) in the UK currently recommends that evidence on the safety and efficacy of transcutaneous electrical stimulation of the trigeminal nerve for ADHD is inadequate in quality and quantity, and that it should only be used in the context of research.[199]