LMMG New Medicine Recommendation

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1 LMMG New Medicine Recommendation Lisdexamfetamine (Elvanse ) for the treatment of ADHD in children and young adults LMMG Recommendation: Red (Restricted) Lisdexamfetamine (Elvanse ) is recommended for use in the treatment of ADHD in children and young adults only in complex patients who meet both of the following criteria. extenuating circumstances exist which mean that a patient would not reliably receive all the required doses of dexamfetamine throughout the day and requires a once daily dose of lisdexamfetamine to support adherence treatment has been agreed through the internal governance arrangements of the trust. Summary of supporting evidence: Several short-term placebo-controlled trials support the efficacy of lisdexamfetamine, and there are some limited data from long term follow-up of some patients to 26 weeks. Direct comparative data are currently limited to a 9-week trial of lisdexamfetamine compared with atomoxetine in patients with moderate to severe ADHD who had previously had an inadequate response to methylphenidate. Those taking lisdexamfetamine achieved a faster treatment response, and a higher proportion achieved improved symptoms and global functioning, compared with patients treated with atomoxetine over 9-weeks of followup. There appear to be a number of limitations to the direct comparative trial: o patients with common comorbidities in people with ADHD were excluded from the trial. o the trial precluded dose titration after visit 3, which was then considered to be the optimised dose used throughout the maintenance period. The study authors note that the time for atomoxetine to reach its maximum effect is typically longer than this 16. o drop out from this short-term trial was 25% in both treatment arms and the most common reason for discontinuation of atomoxetine was lack of efficacy. The trial data were analysed using the method of last observation carried forward, which may have introduced bias in favour of the faster acting lisdexamfetamine in the final assessments of response. o atomoxetine was dosed once daily in the comparative trial, but the SPC notes that patients who do not achieve a satisfactory clinical response (in terms of tolerability or efficacy) when taking atomoxetine as a single daily dose might benefit from taking it as twice daily evenly divided doses in the morning and late afternoon/early evening 17. It is possible that outcomes with atomoxetine relative to lisdexamfetamine would be different if twice daily dosing was permitted. o efficacy measures employed in the trials were necessarily subjective. It is possible that differences in side effects of stimulants and atomoxetine may have revealed treatment assignment in some patients and influenced subjective assessments of 1

2 response. There are no direct comparative data for once daily lisdexamfetamine versus twice or three times daily dexamfetamine. SMC concluded that the economic case for lisdexamfetamine had been demonstrated when compared against atomoxetine, based on data from the direct comparative trial and relevant costs. The observed adverse event profile of lisdexamfetamine is consistent with the known adverse events of other stimulant agents. Cardiovascular and metabolic effects require monitoring, as is the case with other stimulants and atomoxetine. The long acting, pro drug formulation of lisdexamfetamine is considered by the company to reduce the potential for misuse. Nonetheless, the Advisory Council on Misuse of Drugs has recommended to the Home Office that lisdexamfetamine should be a Schedule 2 controlled drug. Lisdexamfetamine appears to be more costly than dexamfetamine across the majority of the daily dose range. Details of Review Name of medicine (generic & brand name): Lisdexamfetamine (Elvanse ) 1 Strength(s) and Form(s): Capsules, 30mg, 50mg and 70mg 1 Licensed indication(s): Lisdexamfetamine is indicated as part of a comprehensive treatment programme for attention deficit/hyperactivity disorder (ADHD) in children aged 6 years of age and over when response to previous methylphenidate treatment is considered clinically inadequate. 1 Reason for Review: Requested by Dr Tim Morris, Child Psychiatry for use in ADHD Proposed use (if different from or in addition to licensed indication above): Use as 2 nd or 3 rd line intervention in ADHD after methylphenidate. Long acting formulation and ability to take without food and dissolvable in water may give therapeutic advantage. Cost is similar to other preparations. Lisdexamfetamine was considered by LMMG in October 2013 and was not recommended and given a BLACK traffic light. This formulary position was reconsidered in October 2014 following requests from specialists to use Lisdexamfetamine in a small cohort of specialist patients. The recommended place in therapy was amended following this reconsideration. 2

3 Background and context In people with attention deficit hyperactivity disorder (ADHD), insufficient production of norepinephrine and dopamine in parts of the brain may lead to symptoms of forgetfulness, distractibility, impulsivity, and inappropriate social behaviours. 2 In general, ADHD is a persisting disorder. Of the young people with a sustained diagnosis, most will go on to have significant difficulties in adulthood, which may include continuing ADHD, personality disorders, emotional and social difficulties, substance misuse, unemployment and involvement in crime. 3 NICE Clinical Guideline 72 recommends group-based parent-training and education programmes with psychological treatment for the child or young person usually as the first line treatments for the treatment of ADHD with moderate impairment. Drug treatment should be reserved for children and young people with ADHD who have severe symptoms and impairment, or for those with moderate levels of impairment who have refused non-drug interventions, or whose symptoms have not responded sufficiently to non-pharmacological interventions. 3 NICE Technology Appraisal 98 4 concluded that methylphenidate, atomoxetine and dexamfetamine were clinically effective and cost effective treatment options, and the choice of drug should be led by factors including comorbid conditions (e.g. tic disorders, Tourette's syndrome, epilepsy), adverse effects, compliance and convenience issues (e.g. need for mid-day dosing at school), patient/carer preferences, and potential for diversion and misuse. The Clinical Guideline recommends that drug treatment is initiated by professionals with expertise in ADHD who should consider: methylphenidate for ADHD without significant comorbidity methylphenidate for ADHD with comorbid conduct disorder methylphenidate or atomoxetine when tics, Tourette's syndrome, anxiety disorder, stimulant misuse or risk of stimulant diversion are present atomoxetine if methylphenidate has been tried and has been ineffective at the maximum tolerated dose, or the child or young person is intolerant to low or moderate doses of methylphenidate 3. Modified-release preparations of methylphenidate should be considered for convenience, improving adherence and reducing issues related to administration during school hours. Alternatively, immediate-release preparations of methylphenidate may be considered if more flexible dosing regimens are required, or during initial titration to determine correct dosing levels 3. Dexamfetamine is considered in the Technology Appraisal to be less suitable for first-line use due to its greater potential for diversion and misuse 4. The Clinical Guideline recommends dexamfetamine in children and young people who are unresponsive to maximum tolerated doses of methylphenidate or atomoxetine 3. Lisdexamfetamine is a long-acting pro-drug of dexamfetamine that permits once daily dosing. It is converted to the active drug primarily via enzymes in the red blood cells, which the company suggests would reduce its potential for misuse. Nonetheless, the Advisory Council on the Misuse of Drugs has recently recommended to the Home Office that lisdexamfetamine should be categorised as a Schedule 2 controlled drug due to a potential for harm and risk of diversion that is 3

4 similar to dexamfetamine 1. It has been requested by a Child Psychology consultant for formulary inclusion as a second or third line treatment after methylphenidate treatment. Evidence in Proposed Use Summary of Efficacy Data in Proposed Use: There are several US-based short-term trials of lisdexamfetamine that demonstrate its efficacy compared with placebo 6-9. However, this evidence review focuses on the available comparative data and most applicable placebo-controlled trial. It draws on the overview of key efficacy and safety data included in the advice on lisdexamfetamine issued by the Scottish Medicines Consortium (SMC) in April , supplemented with recent published comparative data 16. Direct comparative data are available from a published 9-week, phase III, double-blind RCT of lisdexamfetamine against atomoxetine 16. Patients: Children and adolescents aged 6 to 17 years (n=267) with at least moderate severity ADHD (defined as a ADHD-RS-IV total score >28 on a scale of 0 to 54) and with a history or current inadequate response to methylphenidate treatment were included. Those with previous treatment with more than one course of methylphenidate were excluded, as were those with conduct disorder, or history of Tourette s disorder, tics or seizures. Baseline disease severity was similar among the trial arms. Interventions and Comparators: Patients were randomised (1:1) to lisdexamfetamine (30 to 70mg once daily) or atomoxetine (10 to 100mg once daily), which were titrated as per their SPCs over the first 4 weeks, followed by a 5-week maintenance phase. Outcomes: Around 25% of patients randomised to each arm failed to complete the 9-week study for various reasons. The primary endpoint was median time to first clinical response, defined as a Clinical Global Impression Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). This was achieved significantly quicker with lisdexamfetamine (12 days; 95% CI 8 to 16 days) than with atomoxetine (21 days; 95% CI 15 to 23 days) (p=0.001). The proportion of patients achieving response by week 9 was significantly greater with lisdexamfetamine compared with atomoxetine treatment (81.7% vs. 63.6%; p<0.001; NNT=6), as was the least squares mean difference from baseline in ADHD-RS-IV total score and its inattentiveness and hyperactivity/impulsivity subscales. One European 7-week trial compared lisdexamfetamine against placebo, and incorporated a modified-release methylphenidate reference arm 10. Patients: Children and adolescents aged 6 to 17 years (n=336) with at least moderate severity ADHD (defined as a ADHD-RS-IV total score >28) % were treatment naïve, and those who had previously failed to respond to the modified-released methylphenidate were excluded, as were those with conduct disorder, or history of Tourette s disorder, tics or seizures. Baseline disease severity was similar among the trial arms. Interventions and Comparators: Patients were randomised (1:1:1) to once daily lisdexamfetamine (30 to 70mg daily) or placebo or modified-release methylphenidate (18 to 54mg daily), all of which were over-encapsulated to appear identical. During the first 4 weeks, doses were titrated upwards at weekly intervals until at least a 30% reduction in baseline ADHD-RS-IV was achieved. Doses were maintained for the remaining 3 weeks. Outcomes: Around 29-33% of patients randomised to active treatment, and 61% of patients randomised to placebo, failed to complete the 7-week study. The primary endpoint was the change from baseline in ADHD-RS-IV total score. From a mean score of around 41, the difference between lisdexamfetamine and placebo was significant (-18.6; 95% CI: to -15.7; p<0.001), as was the difference between modified-release methylphenidate and placebo (-13.0; 95% CI: to -10.2; p<0.001). Compared with placebo (14%), the proportion of patients achieving CGI-I score 4

5 of 1 or 2 was also significantly greater with lisdexamfetamine (78%) and methylphenidate (61%) 10. The SMC advice notes that there were significant differences in health-related quality of life for active treatments versus placebo. There were no comparisons of any outcomes between lisdexamfetamine and methylphenidate. The Summary of Product Characteristics (SPC) for lisdexamfetamine includes brief details of a double-blind withdrawal study conducted in children and adolescents. Eligible patients enrolled from the placebo-controlled trial above, or newly enrolled patients, who had received 26 weeks of dose-optimised lisdexamfetamine were randomised to continue lisdexamfetamine or receive placebo over 6 weeks. The proportion of patients with treatment failure (defined as a 50% increase in the ADHD-RS-IV total score and a 2-point increase in the CGI-S score compared to scores at entry) was significantly lower for the lisdexamfetamine recipients subjects compared to placebo (15.8% versus 67.5%; p<0.001). For the majority of subjects (70.3%) who were treatment failures regardless of treatment, ADHD symptoms worsened at or before the week 2 visit following randomisation 1. A further double-blind withdrawal study enrolled adults (n=123) who met DSM-IV criteria for ADHD and who, at study entry, had been treated with lisdexamfetamine for a minimum of 6 months. It is reported in the SPC that a significantly lower proportion of patients randomised to lisdexamfetamine met relapse criteria (defined as a 50% increase in the ADHD-RS-IV total score and a 2-point increase in the CGI-S score compared to scores at entry) compared to patients receiving placebo (8.9% versus 75.0%) in the withdrawal phase. However, details of the length of follow-up are lacking. Summary of Safety Data: In the direct comparative trial, the incidence of treatment emergent adverse effects was similar for lisdexamfetamine and atomoxetine (71.9% vs. 70.9%, respectively), with a small minority being classed as severe (5.5% vs. 3.0%). Decreased appetite (25.8% vs. 10.4%) decreased weight (21.9% vs. 6.7%) and insomnia (11.7% vs. 6.0%) were among those adverse events more common with lisdexamfetamine, consistent with its stimulant effects. Somnolence (11.9% vs. 3.1%), upper abdominal pain (7.5% vs. 2.3%) and vomiting (9.7% vs. 4.7%) were among those more common with atomoxetine. Both drugs resulted in increases in mean systolic and diastolic blood pressure, and pulse rate. The incidence of potentially clinically important ECG parameters was similar in both groups. Overall rates of discontinuations due to adverse events were similar (6.3% vs. 7.5%, respectively). Those leading to discontinuation of lisdexamfetamine were: agitation, decreased weight, excoriation, indifference, irritability, nausea, somnolence and tic. The adverse events leading to discontinuation of atomoxetine were headache, irritability, epigastric discomfort, fatigue, influenza, malaise, nausea, sedation, somnolence and upper abdominal pain 16. The SPC for lisdexamfetamine reports brief results of abuse-potential studies. When equivalent oral doses of 100 mg lisdexamfetamine dimesylate and 40 mg immediate-release dexamfetamine sulphate were administered to individuals with a history of drug abuse, lisdexamfetamine dimesylate 100 mg produced subjective responses on a scale of Drug Liking Effects (primary endpoint) that were significantly less than dexamfetamine immediate release 40 mg. However, oral administration of 150 mg lisdexamfetamine dimesylate produced increases in positive subjective responses on this scale that were comparable to the positive subjective responses produced by 40 mg of oral immediate-release dexamfetamine and 200 mg of diethylpropion. Intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring Drug Liking, Euphoria, Amfetamine Effects, and "Benzedrine Effects" that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous dexamfetamine 1. 5

6 The SMC advice reports company data on file that suggests non-medicinal use of lisdexamfetamine is similar to that observed with modified release methylphenidate based on postmarketing surveillance data from the US 14 ; however, details are lacking. Summary of Evidence on Cost Effectiveness and Patient Outcomes: The SMC advice includes brief details of a cost utility analysis comparing lisdexamfetamine against atomoxetine in children aged 6 years and older who have had an inadequate response to methylphenidate. The economic model extrapolates data from the direct comparative trial over a one year time horizon, and it is assumed that patients who respond to treatment in the first 28 days continue on that treatment and maintain their response level over the whole year. Those who fail to respond or discontinue due to intolerance are assumed to have no further treatment in the base case analysis. Taking into account acquisition costs (based on the doses observed in the comparative trial), administration and monitoring costs, lisdexamfetamine was estimated to be more costly by 72 per patient and to generate more QALYs, resulting in an incremental cost per QALY gained of around 7,000. A scenario analysis was presented in which those not responding to treatment could receive an additional line of therapy those not responding to atomoxetine are assumed to receive dexamfetamine and those not responding to lisdexamfetamine could go on to receive atomoxetine. This increased the incremental cost per QALY gained to around 9,700. A range of other sensitivity analyses were conducted, in which all estimates of the incremental cost per QALY gained were below 18,000 using utility values previously accepted by NICE. Alternative utility values increased the estimate to 21,239 per QALY gained. The SMC concluded that, despite some uncertainties, the economic case had been demonstrated 14. Key Points to Note from the Available Evidence: Several short-term placebo-controlled trials support the efficacy of lisdexamfetamine, and there are some limited data from long term follow-up of some patients to 26 weeks. Direct comparative data are currently limited to a 9-week trial of lisdexamfetamine compared with atomoxetine in patients with moderate to severe ADHD who had previously had an inadequate response to methylphenidate. Those taking lisdexamfetamine achieved a faster treatment response, and a higher proportion achieved improved symptoms and global functioning, compared with patients treated with atomoxetine over 9-weeks of followup. There appear to be a number of limitations to the direct comparative trial: o patients with common comorbidities in people with ADHD were excluded from the trial. o the trial precluded dose titration after visit 3, which was then considered to be the optimised dose used throughout the maintenance period. The study authors note that the time for atomoxetine to reach its maximum effect is typically longer than this 16. o drop out from this short-term trial was 25% in both treatment arms and the most common reason for discontinuation of atomoxetine was lack of efficacy. The trial data were analysed using the method of last observation carried forward, which may have introduced bias in favour of the faster acting lisdexamfetamine in the final assessments of response. o atomoxetine was dosed once daily in the comparative trial, but the SPC notes that patients who do not achieve a satisfactory clinical response (in terms of tolerability or efficacy) when taking atomoxetine as a single daily dose might benefit from taking it as twice daily evenly divided doses in the morning and late afternoon/early 6

7 evening 17. It is possible that outcomes with atomoxetine relative to lisdexamfetamine would be different if twice daily dosing was permitted. o efficacy measures employed in the trials were necessarily subjective. It is possible that differences in side effects of stimulants and atomoxetine may have revealed treatment assignment in some patients and influenced subjective assessments of response. SMC concluded that the economic case for dexamfetamine had been demonstrated when compared against atomoxetine, based on data from the direct comparative trial and relevant costs. The observed adverse event profile of lisdexamfetamine is consistent with the known adverse events of other stimulant agents. Cardiovascular and metabolic effects require monitoring, as is the case with other stimulants and atomoxetine. The long acting, pro drug formulation of lisdexamfetamine is considered by the company to reduce the potential for misuse. Nonetheless, the Advisory Council on Misuse of Drugs has recommended to the Home Office that lisdexamfetamine should be a Schedule 2 controlled drug. Productivity, Service Delivery and Implementation Considerations: Use of this drug would not be anticipated to impact on service delivery. Innovation, Need and Equity Considerations: The NICE TA 98 4 recommended methylphenidate, atomoxetine and dexamfetamine as treatment options for ADHD. Dexamfetamine was considered less suitable for first-line use due to its potential for diversion and abuse, rather than on grounds of its efficacy and cost effectiveness. Lisdexamfetamine is specifically licensed for use when response to methylphenidate has been clinically inadequate. Based on current NICE guidance, relevant comparators would include atomoxetine and dexamfetamine. Atomoxetine is not classed as a stimulant and is not subject to controlled drug regulations, and may be dosed once or twice daily depending on tolerability and response. Time to response is typically greater than required with stimulants, as observed in the comparative trial above 16. Dexamfetamine is a stimulant and is dosed two or three times daily and is a schedule 2 controlled drug. The long-acting formulation of lisdexamfetamine therefore offers potential advantages in terms of dose frequency and convenience compared with dexamfetamine, but evidence of a reduced potential for diversion and abuse is limited and it is still recommended a schedule 2 controlled drug. The requesting consultant also noted that lisdexamfetamine offers flexible dosing in patients with swallowing difficulties (as the capsule contents may be dispersed in water) and is also licenced for use in adults. The number of patients in whom this presents an advantage is unclear. The following table summarises lisdexamfetamine against its comparators with respect to the properties specified by the requesting consultant: Table 1: Comparison of properties of lisdexamfetamine against other relevant comparators Drug name Once daily dosing Can be taken without food Options if swallowing difficulties Licensed for use / continued use in adults Atomoxetine X 7

8 (Strattera ) Dexamfetamine 13 X Not documented in X available reference sources Lisdexamfetamine (Elvanse ) Recommended Place in Therapy Lisdexamfetamine (Elvanse ) is not recommended for use in the treatment of ADHD in children and young adults Financial and Service Implications Comparative unit costs: The following table demonstrates the annual acquisition costs for lisdexamfetamine and relevant comparators in patients who have had an inadequate response to methylphenidate. Table 2. Example annual acquisition costs of lisdexamfetamine and potential comparators Drug name Example regimen Annual maintenance cost per patient (ex VAT) Lisdexamfetamine (Elvanse ) 30mg to 70mg once daily* 757 to 1081 Atomoxetine (Strattera ) 10mg to 100mg* daily 812 to 1,083 Dexamfetamine (Non-proprietary) 5mg to 20mg daily in divided 246 to 983 doses Costs based on MIMS list prices as of September This table does not imply therapeutic equivalence of drugs or doses. *Approximate mean daily doses observed in comparative trial: lisdexamfetamine 50mg (annual cost 892); atomoxetine 40mg (annual cost 812). Anticipated patient numbers and net budget impact: The requesting clinician estimated numbers to be treated across paediatric services in East Lancashire Health Economy are The basis of this estimate is unclear. The NICE evidence summary reports the manufacturer s estimate of 116 children and young people aged 6-17 years being treated for ADHD per 100,000 of the UK population. Of these the manufacturer s cumulative estimated uptake of lisdexamfetamine is 3 patients per 100,000 in the first year, 7 patients per 100,000 in the second year and 13 patients per 100,000 in the third year. Across, Lancashire this would equate to would be 1,764 young people with ADHD, of which 46 in the first year, 106 in the second year and 198 in the third year would receive lisdexamfetamine, respectively. The bases of this uptake estimate, and the current ADHD treatment options that are assumed would be displaced, are also unclear. epact data for the last quarter in 2012/13 is summarised in the following table: 8

9 Table 3: Prescribing data across Lancashire for ADHD treatments (last quarter 2012/13) Commissioning Organisation Atomoxetine Hydrochloride Dexamfetamine Sulfate Methylphenidate Hydrochloride Grand Total PCT BLACKBURN WITH DARWEN CCG 4, , , , PCT BLACKPOOL CCG 14, , , , PCT CHORLEY AND SOUTH RIBBLE CCG 6, , , , PCT EAST LANCASHIRE CCG 14, , , , PCT FYLDE & WYRE CCG 7, , , PCT GREATER PRESTON CCG 6, , , , PCT LANCASHIRE NORTH CCG 3, , , , PCT WEST LANCASHIRE CCG 2, , , , Grand Total 59, , , , These data suggest current prescribing of dexamfetamine accounts for less than 10% of total ADHD prescribing costs. If it is assumed that the daily dose of lisdexamfetamine is 50mg (as per the approximate mean dose used in the comparative trial), and further that the maintenance daily dose of dexamfetamine is 10mg, the additional annual cost across Lancashire of the use of lisdexamfetamine in the children in whom the requesting clinician estimates use would range from 8000 to 12,000. Using the manufacturers uptake figures, the additional cost across Lancashire would be 18,400 in year 1 (based on 46 patients), 42,400 in year 2 (based on 106 patients), and 79,200 in year 3 based on 198 patients). If the maintenance daily dose of dexamfetamine was 20mg, the use of lisdexamfetamine 50mg daily would be cost saving. This assumes that lisdexamfetamine would not be used in people in whom atomoxetine is an option. Impact of Implementation: No specific impacts of implementation are anticipated although the economic model submitted to SMC suggested there would be lower number of follow-up appointments and therefore reduced costs with the use of lisdexamfetamine. However, the SPC suggests monitoring requirements are similar to other stimulant medications so it is unclear if this would be the case in practice. 9

10 References 1. Shire. Summary of Product Characteristics - Elvanse 30mg, 50mg and 70mg capsules; February Accessed 30 July 2013 at: es,+hard/#indications 2. National Institute for Health and Clinical Excellence. ESNM19: Attention deficit hyperactivity disorder in children and young people: lisdexamfetamine dimesylate. Accessed 28 August 2013 at: 3. National Institute for Health and Clinical Excellence. Clinical Guideline 72: Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults. Accessed 28 August 2013 at: 4. National Institute for Health and Clinical Excellence. Technology Appraisal Guidance 98: Methylphenidate, atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Accessed 28 August 2013 at: 5. BNF 65, March September 2013; page xii and p Biederman J, Boellner SW, Childress A, Lopez FA, Krishnan S, Zhang Y (2007): Lisdexamfetamine dimesylate and mixed amphetamine salts extended release in children with ADHD: double-blind, placebo-controlled, crossover analog classroom study. Biol Psychiatry 2007;62: Biederman J, Krishnan S, Zhang Y, McGough JJ, Findling RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/ hyperactivity disorder: a phase III, multicentre, randomised, double-blind, forced-dose, parallel-group study. Clinical Therapeutics; vol 29, number 3, 2007, p Findling RL, Childress AC, Cutler AJ, Gasior M, Hamdani M, Ferreira-Cornwell MC, Squires L. Efficacy and safety of lisdexamfetamine dimesylate in adolescents with attention-deficit/ hyperactivity disorder: Journal of the American Academy of Child Psychiatry, vol 50, number 4; April Jain R, Babcock T, Burtea T, Dirks B, Adeyi B, Scheckner B, Lasser R, Renna J, Duncan D: Efficacy and safety of lisdexamfetamine dimesylate in children with attention-deficit/ hyperactivity disorder and recent methylphenidate use. Advances in Therapy (2013) 30: Coghill D, Banaschewski T, Lecendreux M, et al. European randomized phase 3 study if lisdexamfetamine dimesylate in children and adolescents with attention-deficit/ hyperactivity disorder. European Neuropsychpharmacology In Press: doi: /j.euroneuro The North East Wales Trust (NEWT) Guidelines, first edition 2006; p Shire. Summary of Product Characteristics - Equasym 10mg, 20mg and 30mg capsules; October Accessed 06 September 2013 at: 0+mg+Capsules/ 13. Auden Mckenzie (Pharma Division) Ltd. Summary of Product Characteristics Dexamfetamine 5mg tablets; revision Scottish Medicines Consortium. Lisdexamfetamine dimesylate, 30mg, 50mg & 70mg capsules (Elvanse ) SMC No. (863/13); May Accessed 06 September 2013 at: 10

11 ylate_elvanse/lisdexamfetamine_dimesylate_elvanse 15. MIMS July 2013, p Dittmann RW, Cardo E, Nagy P, et al. Efficacy and safety if lisdexamfetamine dimesylate and atomoxetine in the treatment of attention deficit/hyperactivity disorder: a head-to-head, randomized, double-blind, phase IIIb study. CNS Drugs Doi: /s [Epub ahead of print]. 17. Eli Lilly and Company limited. Summary of Product Charecteristics Strattera; May Accessed 13 September 2013 at: mg%2c+40mg%2c+60mg%2c+80mg+or+100mg+hard+capsules./ 18. Advisory Council of the Misuse of Drugs. Lisdexamfetamine advice; 05 September Accessed 14 th September at: D_advice_Lisdexamfetamine.pdf. Strattera 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or 100mg hard capsules; May Accessed 13 September 2013 at: +40mg%2c+60mg%2c+80mg+or+100mg+hard+capsules./ Staffordshire and Lancashire Commissioning Support Unit, The information contained herein may be superseded in due course. All rights reserved. Produced for use by the NHS, no reproduction by or for commercial organisations, or for commercial purposes, is allowed without express written permission. Staffordshire and Lancashire Commissioning Support Unit, Jubilee House, Lancashire Business Park, Leyland, PR26 6TR Tel: