The Use of Lisdexamfetamine in Clinical Practice at a Danish Child Psychiatric Outpatient Clinic Aimed at School Children (Age 7-13 Years) With Attention Deficit Disorders

Background

Attention deficit hyperactivity disorder (ADHD) is characterised by the core symptoms of inattention, hyperactivity and impulsivity, which are excessive for the person's age and developmental status. It is a clinical diagnosis based on observed and reported behavioural symptoms. Two main diagnostic systems are used currently, the International Classification of Diseases 10th revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). Both systems require presence of symptoms in several settings such as school, home life and leisure activities as well as the presence of functional impairment due to symptoms of ADHD (e.g. impairment of psychological, social and/or educational functioning). Symptoms should be evident in early life; for ICD-10 by age 7 and for DSM-5 by age 12. Overall, the diagnostic criteria of ADHD are less stringent according to DSM-5 compared to ICD-10, which is reflected by a higher prevalence of ADHD in populations where the DSM-5 diagnostic criteria are applied. A systematic review (Sayal et al.) from 2018 of 55 studies (25 from the USA, seven from the UK, and 23 outside the USA and UK) reported a prevalence of ADHD in children and adolescents varying from approximately two to seven percent depending mostly on the diagnostic criteria, making it one of the most common psychiatric disorders in children and adolescents.

In Denmark the ICD-10 diagnostic system is used. The National Institute for Health and Care Excellence (NICE) as well as The National Clinical Guidelines from the Danish Health Authority recommend pharmacological treatment for children and adolescents with moderate to severe ADHD. Severity is determined by a clinical assessment based on number of symptoms and functional impairment. Both guidelines recommend the use of methylphenidate (MPH) as the first choice of treatment. In the event that the use of MPH is non-effective in an adequate dosage or results in adverse effects, it is recommended to switch to atomoxetine (ATX), dexamfetamine (DX) or lisdexamfetamine (LDX). The subsequent choice of medication should take into consideration the adverse effect profiles and duration of effect of the different drugs as well as the reason for the switch.

In February 2013, Elvanse (LDX) received marketing authorization in the UK and Europe. It became available for sale for the treatment of ADHD in children and adolescents in Denmark in April 2013.

LDX is an inactive prodrug which is gradually activated to DX by means of peptidase enzymes in the red blood cells. Thus, LDX is a controlled-release drug where a single dose has an effect on the ADHD core symptoms for up to 13 hours. The formulation as a prodrug reduces its potential for abuse. According to www.medstat.dk which is based on data from the Danish Register of Medicinal Product Statistics (LSR), the sales of lisdexamfetamine has been steadily increasing during the years it has been on the market in Denmark.