Methylphenidate, atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents
This is an extract from the guidance. The complete guidance is available at guidance.nice.org.uk/ta98
3 The technology
3.1.1 Methylphenidate is a CNS stimulant. It is licensed as part of a comprehensive treatment programme for ADHD, under specialist supervision, where remedial measures alone prove insufficient. It is a Schedule 2 controlled drug and is not currently licensed for use in children less than 6 years old. It is available in immediate-release tablets (Ritalin, Cephalon; Equasym, UCB Pharma) that are usually given in two or three daily doses. Methylphenidate is also available in modified-release formulations that enable once-daily dosing (Concerta XL, Janssen-Cilag; Equasym XL, UCB Pharma).
3.1.2 Treatment with immediate-release formulations of methylphenidate should be initiated at a dose of 5 mg once or twice daily, and increased if necessary to a maximum of 60 mg per day.
3.1.3 There are two modified-release formulations of methylphenidate. Concerta XL (Janssen-Cilag) is formulated to replace three times daily dosing with the immediate-release formulation and is used where treatment effects are required to persist into the evening. Treatment should be initiated at a dose of 18 mg once daily (in the morning), and increased if necessary up to a maximum of 54 mg once daily. Equasym XL (UCB Pharma) is formulated to be similar to twice-daily dosing with the immediate-release formulation. The recommended dose is 10 mg once daily initially, increased if necessary to a maximum of 60 mg once daily. Alternatively, the initial dose titration may be carried out with the immediate-release formulation.
3.1.4 Methylphenidate should be discontinued if there is no response after 1 month, and treatment should be suspended periodically to assess the child's condition.
3.1.5 Common adverse effects of treatment include insomnia, nervousness, headache, decreased appetite, abdominal pain and other gastrointestinal symptoms, and cardiovascular effects such as tachycardia, palpitations and minor increases in blood pressure. For full details of adverse effects and contraindications, see the relevant Summary of Product Characteristics.
3.1.6 At licensed doses, the annual cost of methylphenidate treatment is as follows:
Ritalin 5–60 mg in one to two divided doses, £34–£407
Equasym 5–60 mg in one to two divided doses, £34–£364
Concerta XL 18–54 mg once daily, £329–£776
Equasym XL 10–60 mg once daily, £304–£730.
Costs are taken from the British National Formulary, 49th edition and exclude VAT. The cost of Equasym XL is based on information supplied by the manufacturer. However, costs may vary in different settings because of negotiated procurement discounts.
3.2.1 Dexamfetamine (Dexedrine, UCB Pharma) is a CNS stimulant. It is licensed as an adjunct in the management of refractory hyperkinetic states in children, under specialist supervision. It is a Schedule 2 controlled drug and is not currently licensed for use in children less than 3 years old. Treatment should be initiated at a dose of 2.5 mg daily for children aged 3–5 years and 5–10 mg daily for children over 6 years, and increased if necessary up to a usual maximum of 20 mg per day (some older children have required 40 mg or more daily for an optimal response).
3.2.2 Common adverse effects are similar to those of methylphenidate. For full details of adverse effects and contraindications, see the Summary of Product Characteristics.
3.2.3 At its usual licensed dose (2.5–40 mg daily), the annual cost of dexamfetamine excluding VAT is £20–£313 (BNF 49). However, costs may vary in different settings because of negotiated procurement discounts.
3.3.1 Atomoxetine (Strattera, Eli Lilly) is licensed for the treatment of ADHD in children 6 years and older and in adolescents, under specialist supervision. It is a selective noradrenaline reuptake inhibitor, although the precise mechanism by which it works on ADHD is unknown. For children/adolescents of up to 70 kg body weight, treatment should be initiated at a dose of 500 micrograms/kg daily, and increased if necessary up to a maximum of 1.8 mg/kg daily, either as a single dose or in two divided doses. For adolescents of over 70 kg body weight treatment should be initiated at a daily dose of 40 mg and increased according to response to a usual maintenance dose of 80 mg.
3.3.2 Common adverse effects of treatment include abdominal pain, decreased appetite, nausea and vomiting, early morning awakening, irritability and mood swings. Increased heart rate and small increases in blood pressure were observed in clinical trials. For full details of adverse effects and contraindications, see the Summary of Product Characteristics.
3.3.3 The annual cost of atomoxetine treatment excluding VAT is £712 when one tablet is given daily, and this doubles to £1424 if two tablets are given daily (BNF 49). However, costs may vary in different settings because of negotiated procurement discounts.