Kiran Hewitt Katie Sims. Dr Alex Day. Reviewed By Ozma Tahir Lead Medicines Information and Clinical Economy Pharmacist, BHFT

Transcription

1 Prescribing Arrangements for the use of methylphenidate, atomoxetine, lisdexamfetamine and amfetamine in adult ADHD (attention deficit hyperactivity disorder) in Berkshire For all referrals of adults with possible or previously diagnosed ADHD requiring further assessment, advice or treatment, the primary contact is Dr Trevor Powell Consultant Psychologist, Neuropsychology Department, 25 Erleigh Road, Reading, Berks RG1 5LR. Tel: The Specialist Adult ADHD Consultant Psychiatrist, Dr James Jeffs is contactable via his secretary as above or by at For all other general mental health issues and illnesses, please use the usual Berkshire Healthcare NHS Foundation Trust s Common Point of Entry (CPE) referral pathway. Useful information for patients' carers and clinicians about ADHD and other mental health conditions can be found at the BHFT "choice and medication" website: Or can be accessed via the Berkshire Healthcare NHS Foundation Trust internet site at: (Click on Services followed by "Medicines") Other Useful Contacts: BHFT Medicines Information Service, Prospect Park Hospital Tel: medicines.information@berkshire.nhs.uk Original Authors Kiran Hewitt Katie Sims Dr Alex Day Lead Clinical Pharmacist, BHFT Senior Clinical Pharmacist, BHFT Consultant Psychiatrist Reviewed By Ozma Tahir Lead Medicines Information and Clinical Economy Pharmacist, BHFT Version 2.1 Addition of section Reviewed; 01/2016 Updates: Addition of lisdexamfetamine; Clarification of referral process; Appendix 4 (clarifies bio-equivalence of modified release Version 2.0 Page 1 of 15

2 methylphenidate preparations) Document History 1.0 First edition Date of Next Review 09/2019 (or sooner if there are changes to national guidelines) Circulation Approved by Dr James Jeffs Ozma Tahir DTC Drug and Therapeutics Committee, BHFT 28/09/2017 Acknowledgements: Leicestershire Partnership Trusts Medicines Strategy Group, for sharing and allowing reproduction of parts of their ADHD shared care agreement 1. Introduction and purpose These guidelines have been produced following NICE guidance issued in 2008 on the use of methylphenidate, atomoxetine and dexamfetamine in children, young people and adults (1). Clear guidelines are necessary to clarify the roles of primary and secondary care providers when using more specialist medicines that are categorised as amber drugs in the NHS Berkshire traffic light system. This document sets out these responsibilities from initial referral to the adult ADHD service through to on-going treatment maintenance and support. 2. About the Service The Adult ADHD clinic aspires to ensure that patients with Adult ADHD get a high quality service that is safe and meets their needs. It is designed solely as a shared-care service and cannot accept patients where there is not a Berkshire GP agreeing to share care. The service provides: diagnostic (re)assessment for ADHD; initiation and titration of ADHD medication; and yearly reviews of the efficacy and necessity of ongoing ADHD treatment. The service does not offer an ongoing prescribing or monitoring function, and cannot provide urgent mental health input. The Service can only operate when Dr Jeff s is present. During periods of absence, any queries should be directed to either CPE or Medicines Information (details on front cover). 3. Disorder Background & Guidance Summary See end, Appendix Formulary Status of ADHD Medications Stimulants are usually the first-choice pharmacological treatment for ADHD in both children and adults 5. Drug Licensed? EPC (BEast) APC (BWest) BHFT DTC Methylphenidate Not in adults Amber 1 st line Amber 1 st line Amber 1 st line Lisdexamfetamine Yes Amber 2 nd or 3 rd line Amber (1 st or 2 nd line under discretion of Amber (1 st or 2 nd line under discretion of Version 2.0 Page 2 of 15

3 Specialist) (APC 02/03/16) Specialist) (DTC Jan 2016) Atomoxetine Yes Amber 2 nd line Amber 2 nd line Amber 2 nd line Dexamfetamine Not in adults Amber 3 rd line Amber 3 rd line Amber 3 rd line The first line choices of medication in adults include; lisdexamfetaine and methylphenidate 8 (adult use for the latter is an unlicensed indication, however, BHFT has approved unlicensed prescribing of methylphenidate for Adult ADHD in view of the supporting evidence 8 ) The second line choice is atomoxetine (but first line for those at risk of substance misuse or drug diversion, or if previous intolerance/unresponsiveness to methylphenidate). The third line choice is dexamfetamine. 5. Bio-equivalence issues with different brands of methylphenidate modified release Appendix 4 Important: Please refer to the full Summary of Product Characteristics (SPC) for each drug for details of side effects, cautions, contraindications and drug interactions via 6. Process and Responsibilities 6.1 Referral into the Service - New patients should follow the process outlined below from step 1. - Patients referred with a confirmed diagnosis who are receiving treatment: For new referrals from private services, those who have just moved into the area, or from other BHFT services (CAMHS see below*), GPs are requested to share care with BHFT in accordance with the guidelines set out below, by completing the form in appendix 5 (Physical Health Form). The Adult ADHD Team will not assume that all appropriate assessment and monitoring has been conducted at and since initiation. *CAMHS referrals: Adolescents with ADHD may require referral to the Adult Service, which is a commissioned shared care service. We therefore request GP agreement to engage shared care for patients transitioning from the Child and Adolescents Mental Health service by completion of the form in Appendix 5 of this document. CAMHS patients would normally be referred at their annual review and so would first be seen by the Adult ADHD Team a year after this. 6.2 Process and Responsibilities STEP 1: GP to send initial referral request for Psychological Assessment to Common Point of Entry (CPE), including patient details and brief summary of concerns. Once a referral is received, the service will perform an initial screen and add the patients name to the waiting list for a neuropsychologist appointment. The patient is then seen for an ADHD psychology assessment, where they would be given a diagnosis of ADHD where appropriate, after which they are placed on the waiting list for an ADHD medical assessment if they are diagnosed with ADHD. STEP 2: Secondary Care Medical ADHD Assessment Version 2.0 Page 3 of 15

4 To assess patient (including full medical, physical and medication history details and carry out a comprehensive assessment, to include: full mental health and social assessment full history including past and present medical and psychiatric disorders or symptoms concomitant medicines history or risk of substance misuse. STEP 3: A request is sent to the patients General Practitioner to complete Physical Health form (appendix 5) with clinical history as set out below: 1. Full history and details of any diagnosis or history where caution is needed for potential medication treatment, including - Assessment of history of exercise syncope, undue breathlessness and other cardiovascular symptoms past and present medical and psychiatric symptoms Full physical assessment should include cardiovascular system examination, weight, blood pressure and heart rate. If there is past medical or family history of serious cardiac disease, a history of sudden death in young family members or abnormal findings on previous cardiac examination, then provide ECG details with interpretation (consult a cardiologist for clarification as needed). Risk assessment for substance misuse and drug diversion. 2. Provide details of current medication. STEP 4: Secondary Care Specialist Responsibilities Initial Consultation/Assessment: 1. Receipt of Physical Health form from GP 2. Provide the initial FP10 prescription for the medication of choice (unless the patient is already receiving prescriptions from GP). 3. Within 4 weeks of initial prescription (and usually within first 2 weeks) review efficiency of the prescribed ADHD drug monitor for side effects and document any problems discussed adjust dose if necessary and correspond with GP as necessary for sharing of information. Take pulse and blood pressure 4. Continue prescribing until patient is stabilised (usually 3-4 months) 5. Once the patient is stable, discharge to GP care for continuation of treatment. GP will be sent outcome information which should include details of continual requirements for monitoring and review. The patient will be invited back to the specialist for a review every twelve months. 6. At the annual review, review progress and communicate findings back to GP. Provide support and advice regarding all aspects of medication prescribed to GP. Offer routine appointment for review at 12 month. Patients who do not attend their annual review Version 2.0 Page 4 of 15

5 appointment will have their name removed from the yearly review list and the GP will be informed. Note: The patient will only be open to the Specialist Service for the time medicines are being initiated and at the time of the annual review appointment. It is not possible to keep the patient open on the Adult ADHD Clinic List at other times as referrals to other services would be delayed should they become necessary. 7. Review progress if requested by GP - change in behaviour; treatment resistance, increased sedation, etc. Notify the GP of the results of any patient reviews, including changes in prescribed dose. Ensure the patient has sufficient medication until the GP has received this information, at least 14 days. 8. Receive and respond to feedback from GP as appropriate, e.g. progress/status of the patient and in particular noting any dose changes/alterations/discontinuation etc. of treatment under the agreement. STEP 5: General Practitioner Responsibilities Maintenance Once patient is stabilised: 1. Issue repeat prescriptions after stabilisation. Methylphenidate, lisdexamfetamine and dexamfetamine are CDs, so prescriptions should be limited to 30 days supply (and are only valid for 28 days from the date of signature). Sustained release methylphenidate preparations need to be prescribed by brand as they are NOT interchangeable (they have different release profiles, see Appendix 4). 2. Continue any required monitoring as per specialist recommendations (will be dependent on the drug prescribed). 3. If there is adequate response to treatment, continue for as long as clinically effective.. The patient will be seen every 12months by the ADHD specialist. Offer GP review at the 6 month point to review continued treatment benefit. This will include evaluation of symptom control, adverse effects experienced, tolerance and patient/carer views. Provide feedback to the specialist if appropriate, as to the progress/status of the patient and in particular notifying of any further dose changes/alterations/discontinuation and emergence of further adverse effects. Contact Specialist at any stage for advice or support. 4. In the event of any concerns arising about ADHD symptoms or medication contact Specialist Consultant for advice on management. 5. To refer patients for prompt specialist cardiac evaluation if symptoms develop such as palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of heart disease. 6. To be alert for signs of diversion, misuse or abuse of methylphenidate. 7. Considerations for trial without treatment There should be a discussion with the patient at the Secondary Care Specialist Annual Review to consider whether the medication is still needed, especially where treatment has continued for 12 months. If there has not already been a trial off medication, consider withdrawal of medication (except if review by specialist has led to an increase in dose). This should be offered and discussed with the patient and the outcome recorded. Consideration must be given to patient choice. Version 2.0 Page 5 of 15

6 Methylphenidate and dexamfetamine can generally be withdrawn by treatment discontinuation, but monitor for signs of withdrawal (uncommon). For atomoxetine, reduce the dose at weekly increments and discontinue over a four week period. If required, refer back to the specialist for advice/guidance on the treatment withdrawal process. 8. Dealing with Emergent Medical Situations Conditions that Would Normally Require Withdrawal of Medication Significant cardiac disease/event (Myocardial infarction, cardiomyopathy, arrhythmia, angina, heart failure, severe tachycardia, significant QTc Prolongation) Malignant or Severe Hypertension Hyperthyroid state Stroke/Cerebrovascular disease Uncontrolled epilepsy (Status epilepticus, worsening seizures) Phaeochromocytoma Severe agitation/acute deterioration in mental state associated with start of ADHD medication Aneurysm/severe vascular disease/vasculitis Glaucoma Clear psychosis/manic episode Chaotic substance misuse on medication See section 9 for advice relating to managing treatment in pregnancy Some Conditions that May Require Expedited Appointment (within 6 weeks) with ADHD Clinic to Review Medication Development of a new side effect of the medication, where the patient is able to tolerate it and there is no acute concern for health (e.g. insomnia, nausea, anxiety) Patient considering pregnancy Developing new Tic Disorder ADHD medications effectiveness not good enough Some Conditions Where other Actions May be Appropriate Persistent mild-moderate elevation in blood pressure where patient is very keen to continue ADHD medication, especially where ADHD medication might not be the cause. Development of new mental health condition not associated in time with changes to ADHD medication. New Family History of heritable cardiac or vascular conditions ECG Abnormality of unknown significance * Check BNF for drug interactions Consider treating hypertension* Referral to Common Point of Entry Refer for appropriate screening and inform ADHD clinic Refer to cardiology, inform ADHD clinic It is impossible to produce guidance to cover all clinical eventualities. This is meant as a helpful prompt to support your clinical decision making. In most cases, ADHD medication can be withdrawn if there is a significant concern relating to it. You can also seek advice from the ADHD consultant ( /6472, though this is a very small service and cannot guarantee an urgent response. Advice can also be sought from CCG pharmacists and the Medicines Information Service at Prospect Park Hospital ( ). Version 2.0 Page 6 of 15

7 9. Pregnancy & Lactation As with most medicines, the safety of these drugs in pregnancy and lactation cannot be guaranteed. For lisdexamfetamine and atomoxetine, there is insufficient data available regarding pregnancy outcome data to be able to make any recommendation. There is most data available about methylphenidate exposure in pregnancy, however, this is still limited and is again, insufficient to make any general recommendations of safety 11. If a patient taking any of these drugs reports a pregnancy or is planning a pregnancy, they should be offered a full risk vs. benefit assessment discussion within primary care. This should include a discussion around breastfeeding after birth. Methylphenidate can be used in the breastfeeding mother if considered clinically appropriate to do so, with extra monitoring for adverse effects in the infant i.e. weight. There is little or no data available about the other alternatives in order to make any specific recommendation (13). The GP can call the Medicines Information Service on , who can give advice on a case by case basis or speak to Dr Jeff s (when available) for further advice. 10. Drug & Dosage Details: Drug Brand Action Dosage Methylphenidate IR Methylphenidate SR Generic Brand names available(ritalin, Equasym, Medikinet ) Xenidate XL tablets CNS stimulant. Schedule 2 controlled drug. Onset: min Duration: 2-4 hours CNS stimulant. Schedule 2 controlled drug. Onset: 30min 2h Duration: 12hours IR:22% ER:78% 5mg TDS up to a max of 100mg daily in divided doses 18mg 108mg once daily Start at 18mg daily. Adjust at weekly intervals. 18mg Concerta = 15mg Ritalin Medikinet XL capsules Equasym XL capsules Lisdexamfetamine Elvanse Adult CNS stimulant. Schedule 2 controlled drug. Onset: min Duration: up to 8 hours IR:50% ER:50% CNS stimulant. Schedule 2 controlled drug. Onset: min Duration: 8 hours IR:30% ER:70% CNS stimulant Schedule 2 controlled drug Onset: 3.5 hours Duration: unclear Atomoxetine Strattera Selective Noradrenaline reuptake inhibitor (not a 10mg 100mg once daily Start at 10mg daily. Adjust at weekly intervals. 10mg to 100mg once daily Start at 10mg daily. Adjust at weekly intervals. 30mg once daily (morning), increased weekly to 50mg then 70mg if necessary For adults of up to 70 kg - initiate at 500 Version 2.0 Page 7 of 15

8 controlled drug) Onset of action: may take 4-6 weeks Can be given as a single dose in the morning OR twice daily last dose no later than early evening. Dexamfetamine generic CNS stimulant Schedule 2 controlled drug Onset: min Duration: 3-6 hours micrograms/kg daily, increase after 7 days, according to response. Maintenance dose mg/kg daily For adults of over 70 kg - initiate at a daily dose of 40 mg for 7 days. Usual maintenance dose mg daily. N.B. May be increased up to 1.8mg/kg daily (max 120mg daily) unlicensed under a specialist. 5mg BD initially. Adjust at weekly intervals up to a max of 60mg daily in divided doses. IR= Immediate Release ER=Extended Release IMPORTANT: Please refer to Summary of Product Characteristics for individual products for side effects, cautions, contraindications and interactions. 10. Costs of Medications See Appendix Monitoring Parameters See Appendix 3 Version 2.0 Page 8 of 15

9 Appendix 1. Disorder Background & Guidance Summary The 2007 Adult Psychiatric Morbidity Survey (APMS) estimates that 8% of adults within England have ADHD (2). ADHD is defined by the core symptoms of inattention, hyperactivity and impulsivity. The diagnostic criteria for the condition are set down in both the DSM IV (Diagnostic and Statistical Manual American Psychiatric Association 2000) and ICD 10 (International Classification of Mental and Behavioural Disorders - World Health Organisation 1992) diagnostic manuals. These criteria require that: The symptoms have persisted for at least six months to a degree that is maladaptive and inconsistent with the development level of the person There must be clear evidence of clinically significant impairment in social or academic/employment functioning Some impairment is present in two or more settings (usually at home, at work and social activities) There is previous evidence of ADHD in childhood The symptoms do not occur exclusively during the course of a pervasive developmental disorder, schizophrenia or other psychotic disorder and are not better accounted for by other mental disorders (such as bipolar disorder, depression or anxiety) Treatment of ADHD in Adults Guidance The first UK clinical guideline on ADHD that covered the disorder in adulthood was published in 2007 by the British Association for Psychopharmacology (BAP) (3). This included a consensus statement on ADHD as a neurodevelopmental condition that continued into adulthood, advice on the assessment and treatment of it, and recommendations on service provision. This was followed in 2008 by the online publication of formal guidance from the National Institute for Health and Clinical Excellence (NICE). The NICE clinical guideline on treatment of ADHD (2008) recognises drug treatment of ADHD as part of a comprehensive treatment programme addressing psychological, behavioural and educational or occupational needs. It considers drug treatment as the first line treatment unless the person prefers psychological treatment. The NICE full guideline (1) recognises that the treatment strategies for ADHD in adults are essentially similar to those used in childhood. It also very importantly states that it remains an anomaly that many drugs that are considered to be safe and effective in children and adolescents are not licensed for use in adults. The British Association for Psychopharmacology s (BAP) evidence based guidelines for management of ADHD (2006) addresses the issue of off-license prescribing as follows:- The BNF (Joint Formulae Committee 2005) states; unlicensed use of medicines becomes necessary if the clinical need cannot be met by licensed medicines; such use should be supported by appropriate evidence and experience. BAP Guidelines further state Although controlled evidence for prescribing in adults is not extensive, this consensus statement can be considered to meet the criteria for adequate evidence and experience when prescribing standard medications to adults with ADHD, when done in the context or with support of specialist psychiatric services. Version 2.0 Page 9 of 15

10 Prescribing for adult ADHD is necessarily off-label since no agent is licensed in adults for this indication (although for atomoxetine and Concerta XL the manufacturers state that in adolescents whose symptoms persist into adulthood and who have shown clear benefit from treatment, it may be appropriate to continue treatment into adulthood. This is because historically ADHD was considered a childhood disorder and patients were expected to grow out of this condition by their late teens. It is now widely recognised that in up to 70% to 80% of patients the condition continues into the adulthood and continues to cause impairment of functioning in a large proportion. Hence these patients need continuation of their treatment. Pharmacological companies are in the process of applying for licenses for these products to be used in adults with ADHD. Drugs covered by the agreement and their place in treatment Stimulants are usually the first-choice pharmacological treatment for ADHD in both children and adults. In the UK, both methylphenidate and dexamfetamine are available, although as yet remain unlicensed for use in adults. There is evidence regarding the safety and effectiveness of stimulants in children, and an increasing amount of evidence for efficacy in adults (5). The second-line choice of medication for ADHD in adults is usually atomoxetine. Atomoxetine is licensed in the US for the treatment of ADHD in both children and adults, although in the UK it is only licensed for treatment of adults who started atomoxetine in childhood or adolescence. Atomoxetine can also be considered as a first line treatment where there is a history of substance misuse, psychosis, or the patient wishes to avoid stimulant medications or has been previously treated effectively with atomoxetine and wishes to restart it. Appendix 2: Cost of Medication Drug Dose Cost/28 days (Drug Tariff Jan 2016/BNF 70) Methylphenidate IR (Medikinet) (first line) 5mg tds 10mg tds 100mg daily (max) Xenidate* (XL) 18mg 36mg Matoride (XL) 54mg od Concerta XL 18mg od 36mg od 108mg od (max) Medikinet XL Medikinet XL Equasym XL 10mg od 30mg od 100mg od (max) 10mg od 30mg od 100mg od (max) 10mg od 30mg od 100mg od (max) Atomoxetine (second line) 40mg od 80mg od 120mg (max specialist) Lisdexamfetamine 30mg Version 2.0 Page 10 of 15

11 50mg mg * Price obtained from AAH Hospital Service Catalogue Aug-Oct 2015 Appendix 3: Monitoring Parameters Parameter Frequency Target Results Action (for GP) on variance Blood Pressure Pulse Weight Appetite FBC LFTs (atomoxetine) Annually * Stability Sustained resting tachycardia, arrhythmia or clinically significant increase in systolic b.p. should prompt dose reduction and referral to other (e.g. cardiac) where appropriate. Approx. 10% patients on atomoxetine may develop more significant rises in b.p. and heart rate with clinical implications. See MHRA warning (4). Annually If there is a specific concern/symptoms of hepatic problem. Results within normal limits Discuss concerns with specialist. Consider monitoring BMI and changing the drug if weight loss persists. Discontinue if neutropenia develops and discuss with appropriate specialist. Atomoxetine may require dose reduction/discontinuation if laboratory or clinical evidence of abnormal hepatic function. Behaviour including selfharming Mental state including emergence of psychotic symptoms, irritability, tics, suicidal thinking or anxiety/panic symptoms At each appointment Annually (by GP or if specialist has been referred to) ( * NICE CG72 recommends every 3 monthly) Able to cope with daily living If unexpected change in behaviour is noted review is indicated. Discuss with secondary care specialist as necessary Version 2.0 Page 11 of 15

12 Appendix 4: Bioequivalence of different brands of methylphenidate modified release preparations There are five different brands of methylphenidate XL, which cannot all be used interchangeably, due to subtle differences in the release profile of methylphenidate; Medikinet XL Concerta XL Equasym XL Xenidate XL Matoride XL Medikinet XL, Equasym XL and Concerta XL ARE NOT BIO-EQUIVALENT AND CANNOT BE INTERCHANGED Concerta XL, is clinically bioequivalent to Matoride ; both release approx. 21% immediate release methylphenidate with the remainder released over time 9. Matoride XL can be prescribed in place of Concerta XL as they are branded generics and so cheaper. The newer preparations Matoride XL and Xenidate XL have been granted replicate marketing authorisation to Concerta XL on the basis that they have satisfied the criteria for a equivalent release profile for the Concerta XL product. Prescribers and pharmacists should be aware of these new preparations available. It would seem appropriate for Matoride XL or Xenidate XL to be considered as alternatives to Concerta XL when initiation of Concerta XL is appropriate in an individual patient. As per BNF advice, prescribers should specify the brand when prescribing Matoride XL or Xenidate XL to ensure the correct product is dispensed. The newer products match Concerta XL in terms of colouring for each prescribable dose, however the tablets are a different shape (though of equivalent size). If there is an intention is to switch patients from Concerta XL to either Matoride XL or Xenidate XL it would be prudent for there to be a discussion with the patient or guardian to ensure that they are aware and happy with the change in preparation 12. Medikinet XL releases 50% as immediate release and the remainder over time and so is not equivalent to Concerta. Equasym XL releases 30% immediately with 70% being released over time and has been shown not to be bio-equivalent to Medikinet XL 10. Medikinet XL, Xenidate XL and Matoride XL are branded generics and so are cheaper than Concerta XL and Equasym XL. When initiating methylphenidate, please ensure you prescribe the same brand every time. Version 2.0 Page 12 of 15

13 Appendix 5: Physical Health Form ADHD Clinic Shared Care Actions. Prior to starting ADHD medication the patient requires a full cardiovascular assessment and examination. Please refer to Shared Care prescribing arrangements. Patient s name: History Please review the patient s record or confirm when you examine the patient. Yes No Unknown Past MI Past Stroke Hypertension Angina Exercise syncope Chest pain on exertion Palpitations Ischaemic Heart Disease Family Hx serious cardiac disease Family Hx stroke/ Transient Ischaemic Attack Hx of sudden death in young member of family Further information if answered yes above: Examination Pulse (rate/rhythm): / Height: Blood Pressure: Weight: Version 2.0 Page 13 of 15

14 Heart sounds: BMI: ECG We do not need to see the ECG but we do need to know it is normal. If any doubt refer to a cardiologist. Yes No Sinus Rhythm QTc Interval: ms I confirm the above details are correct and that the practice would be willing to support ADHD Prescribing for this patient under the shared care agreement if the ADHD Clinic agrees it is appropriate. Signed (by GP) date Name GP Practice (Please print clearly FAX to ADHD Clinic Version 2.0 Page 14 of 15

15 References: 1. NICE CG72. Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults 2. Adult psychiatric morbidity in England, Results of a household survey. The NHS Information Centre for health and social care, British Association for Psychopharmacology 2006; Evidence based guidelines for management of Attention-Deficit/hyperactivity Disorder in Adolescents in transition to Adult Services and in Adults. 4. MHRA UK Public Assessment Report. Atomoxetine: a review of the effects on heart rate and blood pressure. May Retz W, Retz-Junginger P, Thome J, et al. Pharmacological treatment of adult ADHD in Europe. World J Biol Psychiatry 2011 Sep.: SPCs (Summary of Product Characteristics) for Equasym XL, MedikiNet XL, Concerta XL, Strattera and Ritalin. Available online 7. BNF Accessed online. May Maudsley Prescribing Guidelines, 12 th edition, BHFT Mi Databank ref: 8203; Comparing bioequivalence of Medikinet and Xenidate. 10. Communication from Shire Pharmaceuticals. BHFT Mi Databank Project Toxbase. Accessed online 23/02/2016 (monographs for atomoxetine and methylphenidate in pregnancy) 12. Extended-release methylphenidate a review of the pharmacokinetic profiles available. London Medicines Evaluation Network. May Martin Bradley. 13. Medication and Mothers Milk Dr T Hale. Version 2.0 Page 15 of 15