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Switching from Neurostimulant Therapy to Atomoxetine in Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Clinical Approaches and Review of Current Available Evidence

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Abstract

This review provides practical information on and clinical reasons for switching children and young people with attention-deficit hyperactivity disorder (ADHD) from neurostimulants to atomoxetine, detailing currently available evidence, and switching options. The issue is of particular relevance following recent guidance from the National Institute for Health and Clinical Excellence and European ADHD guidelines endorsing the use of atomoxetine, along with the stimulants methylphenidate and dexamphetamine, in the management of ADHD in children and adolescents in the UK.

The selective norepinephrine (noradrenaline) reuptake inhibitor, atomoxetine, is a non-stimulant drug licensed for the treatment of ADHD in children and adolescents, and in adults who have shown a response in childhood. Following the once-daily morning dose, its therapeutic effects extend through the waking hours, into late evening, and in some patients, through to early the next morning. Atomoxetine may be considered for patients who are unresponsive or incompletely responsive to stimulant treatment, have co-morbid conditions (e.g. tics, anxiety, depression), and have sleep disturbances or eating problems, for patients in whom stimulants are poorly tolerated, and for situations where there is potential for drug abuse or diversion. Atomoxetine has been shown to be effective in relapse prevention and there is suggestion that atomoxetine may have a positive effect on global functioning; specifically health-related quality of life, self-esteem, and social and family functioning.

According to one study, approximately 50% of non-responders to methylphenidate will respond to atomoxetine therapy and approximately 75% of responders to methylphenidate will also respond to atomoxetine. Atomoxetine may be initiated by a schedule of dose increases and cross-tapering with methylphenidate. A slow titration schedule with divided doses minimizes the impact of adverse events within the first several weeks of treatment. Atomoxetine may be co-administered with methylphenidate during the switching period without undue concern for adverse events, such as cardiovascular effects (although monitoring of blood pressure and heart rate is necessary). Atomoxetine may be discontinued abruptly and patients may miss the occasional dose without rebound effects or discontinuation syndrome. A trial period of at least 6–8 weeks, perhaps longer, is recommended before evaluation of the overall tolerability and efficacy of atomoxetine.

We conclude that patients with ADHD can be switched from neurostimulants, specifically methylphenidate, to atomoxetine, and may benefit from symptom improvement.

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Acknowledgments

The authors would like to thank Dr Susan Libretto for her contributions to the editing and preparation of this manuscript, and Ms Leigh Mathieson, Ms Nicola Savill, and Ms Lesley Reese for the project management of this review article. Dr Suyash Prasad is a former employee of Eli Lilly where the majority of this work was conducted. He is a current employee of the Cromwell Hospital, London, UK and Genzyme Therapeutics, Oxford, UK. Dr Chris Steer is a clinical investigator and member of the Eli Lilly ADHD advisory board. This work was sponsored by Eli Lilly and Company; however, the authors have received no funding for their writing contributions.

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Prasad, S., Steer, C. Switching from Neurostimulant Therapy to Atomoxetine in Children and Adolescents with Attention-Deficit Hyperactivity Disorder. Pediatr-Drugs 10, 39–47 (2008). https://doi.org/10.2165/00148581-200810010-00005

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