Guidelines for Management of Attention-Deficit Hyperactivity Disorder in Adults

Transcription

1 Guidelines for Management of Attention-Deficit Hyperactivity Disorder in Adults Aims These guidelines aim to provide a structure for assessing and treating ADHD in adults, and aim to be compatible with NICE Guidelines (2008) 1. Background ADHD is a highly heritable (~ ) neurodevelopmental disorder with its onset in childhood, and persistence into adulthood in approximately 43% of cases 3, with impairment persisting in a greater proportion, giving a prevalence for the disorder in adults of % 5. The core symptom triad of Inattention, Hyperactivity, and Impulsivity 6, leads to a variety of functional impairments including in employment, education and relationships 1. Assessment (See Figure 1) Patients may be referred to adult services with a diagnosis of ADHD as a transition from child services, or may be referred for a diagnostic assessment. In either case a full assessment is required, including: the level of impairment persisting; physical and psychiatric co-morbidities; tolerance of previous medications; and physical examination. Adults referred for diagnosis require a more detailed assessment, including a full developmental history, normally from a collateral informant. DSM-IV-TR 6 or ICD-10 7 criteria are used, but DSM-IV-TR is often favoured, as the ICD-10 diagnosis of Hyperkinetic Disorder only identifies a severe subtype of DSM-IV-TR ADHD 1. New diagnoses of ADHD must be based on evidence that the diagnosis had its onset in childhood, with some of the symptoms continuing into adulthood. School reports and childhood educational psychology assessments can be useful. Rating scales for example the Barkley Symptom Scales 8, and the Wender Utah Rating Scale 9 may assist assessment. The ASRS 10 is a screening tool that can be useful in monitoring treatment response. Formal structured interviews (e.g. CAADID) and Neuropsychological testing are not required routinely to make the diagnosis 11. Comorbidity Adults with ADHD have higher rates of comorbid depression, anxiety, substance abuse/dependence, and conduct disorder 12. In addition, ADHD is associated with poorer prognosis in Bipolar Affective Disorder 13 and can be a frequent comorbidity in Autism Spectrum Disorders, and Tic Disorders 14. Comorbidities should be assessed and treated as normal. Some SSRIs can be used with stimulants or Atomoxetine for treatment of depression / anxiety. Methylphenidate is contra-indicated in patients with a history of severe depression, anorexia, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia and psychopathic/borderline personality disorder. 15 Use in these conditions is a matter of clinical judgement. Clinicians without significant experience may wish to take further advice. Care is required when using atomoxetine in patients with a previous history of psychosis. For Treatment Options See Figures 1-6 Methylphenidate and atomoxetine are not licensed for adults newly diagnosed with ADHD and dosage information is based on NICE guidance Initiation takes place in Secondary Care and for GP prescribing follow the OBMH ADHD guidance on the intranet. 16 Special Circumstances Epilepsy - Titrate all stimulant or non-stimulant medications more slowly, and use with caution. If seizures exacerbated, or de novo seizures occur, stop treatment, and consider consulting a tertiary specialist. Atomoxetine is possibly higher risk than methylphenidate. 17 A Tic Disorders Titration should be slow. Atomoxetine may be better in patients with Tic disorders 1. Hyperthyroidism - Listed as contraindication to Methylphenidate and Dexamphetamine , 18, B Risk of Angle Closure Glaucoma Contraindication to stimulants and Atomoxetine A Dexamfetamine is likely to reduce the convulsive threshold; caution is therefore advised in patients with epilepsy. However, there are case reports where amfetamines have been used to increase phenytoin or phenobarbital serum levels in an attempt to increase their antiepileptic action. 19 B In patients with narrow angle glaucoma, atomoxetine may be higher risk than methylphenidate or dexamphetamine. Amphetamines and methylphenidate may cause a transient rise in intraocular pressure which is not associated with closure of the angle. 17 Oxford Health Guidelines 2011 Page 1 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

2 Some Major Interactions (see BNF 18 or electronic data sheet compendium for individual products) C Atomoxetine: MAOIs/RIMAs (Potentially life-threatening 11 ); radrenergic drugs (some antidepressants); high dose Salbutamol; QT prolonging drugs, drugs lowering seizure threshold; Methadone/Tramadol. Dose adjustment and slower titration of atomoxetine may be necessary in those patients who are also taking CYP2D6 inhibitor drugs (e.g. fluoxetine, paroxetine). Stimulants: MAOIs/RIMAs (Potentially life-threatening 11 ); coumarins; antiepileptics; possibly Clonidine. Other Treatments (not Recommended) Some patients may be taking stimulants not licensed in the UK, for example Adderall XR (mixed amphetamine salts). In general these medications should be switched to an alternative stimulant. Whilst NICE accepts (in certain circumstances) the use of Bupropion, Clonidine, Modafinil and Imipramine in children in tertiary services, they are not recommended for ADHD in adults. There is some evidence for using Bupropion in adults, but NICE was concerned about its side effects 1. There is little evidence to support the efficacy and safety of combining Atomoxetine and stimulants 11. Diversion and Substance Abuse 16-29% of students with stimulant prescriptions will be asked to give, sell or trade their medication in their lifetime 20. There is no evidence that childhood stimulant treatment increases risk of adult stimulant abuse. There is insufficient evidence to indicate that treatment of ADHD reduces comorbid substance misuse. Illicit substances, especially stimulant-type drugs can interact with prescribed stimulants 14. C Oxford Health Guidelines 2011 Page 2 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

3 Figure 1: Assessment Age of Onset Diagnosis usually requires onset of symptoms before age 7 6 but NICE recognises onset before age 12 as appropriate in some cases 1. Symptoms Suggest ADHD 6 6/9 Symptoms of Inattention, or 6/9 Symptoms of Hyperactivity / Impulsivity Symptoms Present Before Age 12 Consider Alternative Diagnoses Exclusion Criteria NICE accepts diagnosis in those with Pervasive Developmental Disorder or General Learning Disability Present in Several Settings Impairment in Adult ADHD 1 Occupational Dangerous Driving Activities of Daily Living Relationships Childcare Only during a Psychotic Disorder *Cardiovascular Disorders There have been reports of sudden death in adults receiving medication for ADHD. In children an association between sudden death on amfetamines (methylphenidate and dexamphetamine) and structural cardiac abnormalities has been implied. Severe hypertension, structural cardiac abnormalities, and cardiovascular disease (including arrhythmias) are contraindications to stimulants and cautions against atomoxetine. Pervasive and Enduring Impairment Full Medical/Psychiatric History & Appropriate Physical Examination Ongoing Cardiovascular Problems * Consider Psychosocial Treatment as Alternative to Medication Substance Misuse Significant substance misuse should be treated before ADHD 11, though ongoing use of alcohol or cannabis does not prevent treatment 1. Medical/Family History any Cardiovascular Disease ECG rmal Treat Co-morbidity then Reassess Current Severe Substance Misuse or Severe Mental Illness Medication Indicated as First Line Treatment (See Figure 2) Patient Wants Medication Oxford Health Guidelines 2011 Page 3 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

4 Figure 2: Medical Treatment Algorithm Atomoxetine (second line treatment) Patient Advice: Inform about very rare severe hepatotoxicity (4 cases in >4 million patients, post marketing analysis 11 ), and associated symptoms. If <30 years old warn of risk of increased suicide behaviours Though possibly preferable to stimulants in patients with a history of psychosis, Atomoxetine can worsen psychosis. A history of psychosis is a caution in Atomoxetine. Medication Indicated Current Stimulant Misuse or Severe Past Stimulant Misuse or Associates with Substance Misusers Baseline Tests Physical: Weight, BP and Heart Rate and bloods for LFTs ECG if medical/family history of serious cardiac disease, or indicated by physical examination Prescribe Atomoxetine: If >70kg: Week 1: 40mg daily Week 2: 60mg daily Week 3: 80mg daily If <70kg: Week 1: 0.5mg/kg/day Week 2: 1.2mg/kg/day (tablets available 10mg, 18mg, 25mg, 40mg, 60mg, 80mg.) History of Psychosis Other Drug Diversion Concerns Usually single daily dose, but can be divided b.d. Methylphenidate IR is considered first-line Very Forgetful or Disorganised Immediate Release Methylphenidate (Ritalin, Medikinet, Equasym) Modified Release Methylphenidate (Concerta XL, Equasym XL, Medikinet XL ) Patient Advice: Inform about loss of appetite, insomnia, and rarely psychosis. Give information leaflets about medicine and diagnosis Baseline Tests: Physical Examination including weight, BP and Heart Rate ECG if medical/family history of serious cardiac disease, or indicated by physical examination Review Concomitant medications Prescribing Immediate Release (IR): Week 1: 5mg b.d. or t.d.s. Week 2: 10mg b.d. or t.d.s Titrate dose against side effects & symptoms - maintenance dose may be mg daily. Usually b.d. or t.d.s., but can be q.d.s.(normally last dose should be 4 hrs before bedtime. Prescribing Modified Release (MR): Week 1: 10mg (Equasym or Medikinet); 18mg (Concerta) o.m. Titrate weekly against side effects and symptoms: Max 100mg / day (Equasym or Medikinet) or 72mg (Concerta,) 1 Usually once daily (morning) given with or after breakfast (Concerta XL or Medikinet XL and before breakfast in the case of Equasym XL Assess ongoing effectiveness including using Ratings Scales, for example ASRS 10, after at least 6 weeks. Once dose stable General Practitioners may take over prescribing. (see shared care protocol) If treatment to continue enter monitoring protocol (see Figure 5) Oxford Health Guidelines 2011 Page 4 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

5 Figure 3: Medical Treatment Algorithm Treatment Failure Treatment with Methylphenidate Failed Treatment with Atomoxetine Failed Incomplete Ensure dose maximised Consider increasing number of doses For any other dosage options seek advice from clinician with appropriate experience. Level of on Reasonable Dose Consider Atomoxetine on Reasonable Dose Reconsider Methylphenidate Level of Incomplete Ensure dose maximised If Remains Sub-Optimal If Remains Sub-Optimal Treatment Failures Despite Adequate Trials of Methylphenidate and Atomoxetine Patient Wants Trial of Dexamphetamine Immediate Release Dexamphetamine Week 1: 5mg b.d. Titrate to Symptoms over 4-6 weeks Max 60mg / day Usually b.d. or t.d.s., but can be q.d.s. Discuss Options with Patient Patient Wants Psychosocial Treatment If Partial to Medication Consider Adding Formal Psychosocial Treatment If to Medication Consider Switching to Formal Psychosocial Treatment Figure 4: Managing Side Effects Stimulants: Insomnia Consider reducing number of doses and taking last dose earlier. IR formulation may be better. Insomnia can be a symptom of ADHD, and sometimes stimulants can improve sleep. Psychotic Symptoms Withdraw medication, assess and treat psychosis, consider Atomoxetine Tics Reduce dose; assess pros and cons of treatment; consider Atomoxetine as alternative. Atomoxetine: Suicidal Ideation Associated with Treatment Withdraw drug. Assess and Monitor. If resolved cautiously consider stimulants. Signs of Liver Failure Withdraw drug. Seek urgent medical advice. Stimulants or n-stimulants: Resting Tachycardia, Arrhythmia, Systolic BP >95 th Percentile or Clinically Significant Increase discuss with appropriate physician 1. Perform ECG. Evidence in youths treated with Methylphenidate suggests that in general its effects on BP & Pulse, though extant, are probably not clinically significant 21. Loss of Appetite / Weight - Take medication during/after food. Add calorific snacks. Larger evening meal 11. Seizures Withdraw. Seek medical advice. Consider psychosocial treatment. Specialist advice before trying any alternative medication. Oxford Health Guidelines 2011 Page 5 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

6 Figure 5: Monitoring Protocol on Treatment: Check for Side-Effects (6 weeks after initiation or dose changes, then every 6 months): Atomoxetine Suicidal thoughts, insomnia, constipation, dizziness, dry mouth, loss of appetite, nausea, jaundice, dark urine 11. Also sexual dysfunction should be specifically enquired about. 1 Stimulants Anxiety, irritability, dry mouth, insomnia, loss of appetite, nausea 11. Also, psychotic symptoms 1. Physical Monitoring (All Treatments) 1 : Weight 3 months and 6 months after initiation, then every 6 months Blood Pressure and Heart Rate 3 monthly or following a dose increase Blood Tests and ECG t required routinely Clinical Effectiveness This should be reviewed yearly. Need for social, psychological and occupational support should be assessed. 1 OBMH Shared Care Protocols 16 NICE supports the devolution of monitoring and prescribing to primary care, following initiation and stabilisation, under local shared care protocols OBMH has ADHD shared care agreements with Oxfordshire PCT and Buckinghamshire PCTs for the treatment of children and adolescents and continued prescribing in patients transferred to adult services. Currently the agreement does not cover newly prescribed adult patients The protocols allow for prescribing and monitoring to be devolved to Primary Care, with the agreement of the GP involved, when: The patient s condition is stable The dose of Methylphenidate/Atomoxetine is stable There is an annual review of treatment with yearly drug-free trial to assess benefits of treatment NICE recognises that if there have been periods without treatment information from this can form part of decisions to continue treatment the MHRA drug safety update Jan indicates that patients on methylphenidate should have a yearly drug-free period Under current shared care agreements specialists remain responsible for reviewing the patient regularly at least every 6-12 months, though it is recognised that this may be a telephone review. An annual evaluation of the benefit of treatment is required. In addition specialists remain responsible for ensuring blood pressure, pulse and weight measurements occur. Figure 6: Psychosocial Management NICE Recommendations: CBT for ADHD 1 Self-Esteem Psychoeducation Learning Adaptive Thinking Skills Targets for Psychosocial Intervention 1 Skills: Attention Organisation Planning Patient-Specific Issues: Anger Management Communication Procrastination NICE states: for adults with ADHD, drug treatment should be the first-line treatment unless the person would prefer a psychological approach 1. Where functional impairment persists after medical treatment CBT (group CBT first-line) should be considered. CBT should also be considered where the patient does not want medication, or where their residual functional impairment is mild enough to be managed by CBT alone. Oxford Health Guidelines 2011 Page 6 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins

7 References 1. National Collaborating Centre for Mental Health, commissioned by NICE (2009) Attention Deficit Hyperactivity Disorder. The NICE guideline on diagnosis and management of ADHD in children, young people and adults. The British Psychological Society and The Royal College of Psychiatrists, London. 2. Faraone, S.V., et al (2005) Molecular Genetics of Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry; 57: Mannuzza, S., Klein, R.G., Bonagura, N., Malloy, P., Giampino, T.L., & Addalli, K.A. (1991) Hyperactive boys almost grown up. Archives of General Psychiatry; 48: Simon, V., Czobor, P., Balint, S., Meszaros, A., & Bitter, I (2009) Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. British Journal of Psychiatry: 194: Kessler, R.C. et al (2006) The Prevalence and Correlates of Adult ADHD in the United States: Results from the National Comorbidity Survey Replication. American journal of Psychiatry; 163:4, DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association 7. ICD-10: Classification of Mental and Behavioural Disorders (1992) World Health Organisations. 8. Barkley, A.R., & Murphy, K.R., (2006) Attention-Deficit Hyperactivity Disorder A Clinical Workbook Third Edition. pp The Guilford Press, New York. 9. Ward, M.F., Wender, P.H., & Reimherr, F.W. (1993) The Wender Utah Rating Scale: An Aid in the Retrospective Diagnosis of Childhood Attention Deficit Hyperactivity Disorder. American Journal of Psychiatry; 150: Kessler, R.C., Adler, L., Ames, M., Demler, O., Faraone, S., Hiripi, E., Howes, M.J., Jin, R., Secnik, K., Spencer, T., Ustun, T.B., & Walters, E.E. (2005) The World Health Organization Adult ADHD Self-Report Scale (ASRS): A Short Screening Scale for Use in the General Population. Psychological Medicine; 35: Barkley, R.A. (2010) Attention Deficit Hyperactivity Disorder in Adults. The latest assessment and treatment strategies. Jones and Bartlett Publishers. Sudbury, Massachusetts 12. Biederman, J., Faraone, S.V., Spencer, T., Wilens, T., rman, D., Lapey, K.A., Mick, E., Lehman, B.K., & Doyle, A. (1993) Patterns of Psychiatric Comorbidity, Cognition, and Psychosocial Functioning in Adults with Attention Deficit Hyperactivity Disorder. American Journal of Psychiatry 150:12, Nierenberg, A.A., Miyahara, S., Spencer, T., Wisniewski, S.R., Otto, M.W., Simon, N., Pollack, P.H., Ostacher, M.J., Yan, L., Siegel, R., & Sachs, G.S. (2005) Clinical and Diagnostic Implications of Lifetime Attention-Deficit/Hyperactivity Disorder Comorbidity in Adults with Bipolar Disorder: Data from the First 1000 STEP-BD Participants. Biological Psychiatry; 57: Nutt, D.J., Fone, K., Asherson, P., Bramble, D., Hill, P., Matthews, K., Morris, K.A., Santosh, p., Sonuga- Barke, E., Taylor, E., Weiss, M., and Young, S. (2007) Evidence-Based Guidelines for Management of Attention-Deficit/Hyperactivity Disorder in Adolescents in Transition to Adult Services and in Adults: Recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology; 21(1): Equasym SPC (2010) Shire Pharmaceuticals, Equasym Summary of Product Characteristics. 16. OBMH (2010) Oxfordshire & Buckinghamshire PCTs ADHD Shared Care Arrangements 17. PDD Bazire, S. (2010) Psychotropic Drug Directory. HealthComm UK. 18. BNF (British National Formulary) 19. Martindale: The complete drug reference. Fourth quarter update Wilens, T.E., Adler, L.AA., Adams, J., Sgambati, S., Rotrosen, J., Sawtelle, S., Utzinger, L., & Fusillo, S. (2008) Misuse and Diversion of Stimulants Prescribed for ADHD: A Systematic Review of the Literature. Journal of the American Academy of Child and Adolescent Psychiatry; 47(1): Findling, R.L., Short, E., Manos, M.J. (2001) Short-Term Cardiovascular Effects of Methylphenidate and Adderall. Journal of the American Academy of Child and Adolescent Psychiatry; 40(5): Further Resources NICE (2006) Methylphenidate, Atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Review of Technology Appraisal 13. Barkley, R.A. (2006) Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, Third Edition. The Guilford Press, New York. Milton Keynes, Oxfordshire, Buckinghamshire, Berkshire East and Berkshire West (MOBB) Priorities Forum Policy Statement Oxford Health Guidelines 2011 Page 7 J. Jeffs, O. Macdonald, H. Shaw and M. Perkins