Key points from the evidence

The content of this evidence summary was up-to-date in May 2013. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Summary

Limited evidence from 1 RCT suggests that lisdexamfetamine dimesylate produces clinically meaningful benefits in ADHD symptoms compared with placebo. The adverse effect profile appears similar to other stimulant drugs, although theoretical advantages in terms of improved adherence and reduced abuse potential require further evaluation in clinical practice.

Effectiveness

  • 1 European, 7‑week RCT in around 300 children/young people aged 6–17

  • Both lisdexamfetamine and methylphenidate provided clinically meaningful and statistically significant benefits compared with placebo in controlling symptoms of ADHD (measured using a validated and widely used rating scale ‑ the ADHD RS IV)

  • No fully published randomised controlled trials directly comparing lisdexamfetamine dimesylate with other drugs licensed for treating ADHD

Safety

  • Similar to the safety profile of other stimulant agents. Cardiovascular and metabolic effects require monitoring

Patient factors

  • Less well tolerated than methylphenidate (treatment discontinuations ~5% vs 2%)

  • Monitoring requirements similar to other stimulant medications (cardiovascular height, weight and appetite)

  • Potential improved adherence and reduced abuse potential require further evaluation in practice

  • Proposed schedule 2 controlled drug ‑ to be confirmed

Cost

  • Around £750 to £1100 per year at licensed doses (greater than dexamfetamine and methylphenidate, less than atomoxetine)

Key points

Lisdexamfetamine dimesylate (Elvanse) received a UK marketing authorisation in February 2013 and was launched in the UK in March 2013. It is licensed for use as part of a comprehensive treatment programme for attention deficit hyperactivity disorder (ADHD) in children aged 6 years and over when response to previous methylphenidate treatment is considered clinically inadequate. Lisdexamfetamine dimesylate is a pharmacologically inactive pro‑drug that is converted into the central nervous system stimulant, dexamfetamine.

Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults (NICE guideline CG72, published in 2008) recommends that drug treatment for children and young people with ADHD should always form part of a comprehensive treatment plan that includes psychological, behavioural and educational advice/interventions. It also recommends that when drug treatment of ADHD is considered appropriate, methylphenidate, atomoxetine and dexamfetamine are suitable options within their licensed indications. The decision regarding which product to use should be based on specific criteria listed in the guideline (such as the presence of comorbid conditions).

This evidence summary is based on a European, 7‑week, randomised controlled trial that compared lisdexamfetamine dimesylate with placebo in children and young people aged 6 to 17 years, who had a diagnosis of moderate ADHD. It found that, compared with placebo, lisdexamfetamine dimesylate treatment resulted in statistically significantly greater improvements in the symptoms of ADHD as measured using the ADHD rating scale version IV (ADHD‑RS‑IV, the primary outcome) and the clinician‑rated global impression of improvement. The changes compared with placebo (around 50% decrease in score) were also considered to be clinically meaningful (25–30% decrease in score). A modified‑release methylphenidate reference arm in the trial showed similar results to the lisdexamfetamine dimesylate treatment arm when both drugs were compared with placebo, but there was no direct comparison between the 2 active treatments. At the time of publication, there are no fully published randomised controlled trials that directly compare lisdexamfetamine dimesylate with other drugs licensed for treating ADHD.

Treatment‑emergent adverse events leading to discontinuation of lisdexamfetamine dimesylate were vomiting, anorexia, decreased appetite, tachycardia, decreased weight and insomnia. Lisdexamfetamine dimesylate and modified‑release methylphenidate were both associated with modest increases in mean pulse rate, heart rate, systolic blood pressure and diastolic blood pressure, and decreases in mean body weight from baseline to end point.

Local decision makers will need to consider the place of lisdexamfetamine dimesylate alongside the use of other treatments for ADHD, in the context of the evidence available. There is a greater drug acquisition cost associated with the use of lisdexamfetamine dimesylate compared with dexamfetamine. The NICE guideline on ADHD states that if there is a choice of more than 1 appropriate drug, the product with the lowest cost (taking into account the cost per dose and number of daily doses) should be prescribed. If its status as a controlled drug under Schedule 2 of the Misuse of Drugs Regulations (2001) is confirmed, this may also influence local decision making.

Key evidence

Coghill D, Banaschewski T, Lecendreux M et al. (2013) European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder. European Neuropsychopharmacology: in press

Update

The following information has become available since this ESNM was produced.

September 2015: Availability of lisdexamfetamine for attention deficit hyperactivity disorder (ADHD) in adults

Lisdexamfetamine for ADHD in adults has been launched in the UK as Elvanse Adult. The cost of Elvanse Adult (excluding VAT) is £58.24 for 28×30 mg, £68.60 for 28×50 mg and £83.16 for 28×70 mg capsules. Costs taken from MIMS, September 2015.

June 2014: Amendments to The Misuse of Drugs Act 1971 affecting Tramadol, Zaleplon, Zopiclone and Lisdexamfetamine

On 10 June 2014 amendments to the Misuse of Drugs Act 1971 came into force. These amendments include specification changes for tramadol hydrochloride, zaleplon, zopiclone and lisdexamfetamine. All of these drugs were previously specified as prescription only medicines and are now specified as controlled drugs. The amendments to legislation were recommended to protect the public from the harms associated with misuse of these drugs. In addition the changes bring the specifications of these drugs in line with those of drugs of a similar structure.

Lisdexamfetamine:

  • is now controlled as a Class B drug under the Misuse of Drugs Act 1971

  • is now listed under Schedule 2 of the Misuse of Drugs Regulations 2001

  • is now subject to regulations for its possession, supply, manufacture, import and export.

These amendments were summarised in a medicines evidence commentary.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.