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ADHD IN ADULTS WITH EPILEPSY

ADHD IN ADULTS WITH EPILEPSY. Marlis Frey RN, NP Andres M. Kanner, MD Rush Epilepsy Center Department of Neurological Sciences Rush University Medical Center Chicago, IL, USA. Facts and Myths:. Myths Children outgrow ADHD Facts

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ADHD IN ADULTS WITH EPILEPSY

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  1. ADHD IN ADULTS WITHEPILEPSY Marlis Frey RN, NP Andres M. Kanner, MD Rush Epilepsy Center Department of Neurological Sciences Rush University Medical Center Chicago, IL, USA

  2. Facts and Myths: Myths • Children outgrow ADHD Facts • About 75% of children diagnosed with ADHD will continue to have symptoms through adolescence. • About 65% of children will continue to have impairing ADHD symptoms into adulthood. Faraone et al., 2000

  3. Facts and Myths: • Fact: • 20 to 60% children with epilepsy are expected to experience ADD • Persistence of ADD symptoms into adulthood has yet to be established in these patients.

  4. ADHD in Epilepsy: Potential pathogenic factors • Neuroanatomical structural abnormalities: • Frontal lobe structures • Mesial temporal structures • Disturbances of Neurotransmitter Secretion (Dopamine, norepinephrine). • Genetic • Environmental factors • Iatrogenic

  5. Epidemiology • Prevalence • in children (general population): 4% to 12%. • In children with epilepsy: 20 to 60% • In adults (general population): 2% to 7%. • In adults with epilepsy: ? • Male-to-female ratio (general population): • pediatric: 3:1 • adult: 3:2 • Male-to-female ratio (epilepsy population): ?

  6. DSM-IV CriteriaCore Symptoms of ADHD • Inattention - six or more of the following, manifested often: • Inattention to details/makes careless mistakes • Difficulty sustaining attention • Seems not to listen when spoken to • Fails to finish tasks/does not follow through • Difficulty organizing tasks or activities • Avoids tasks requiring sustained attention • Loses things necessary for tasks/activities • Easily distracted by external stimuli • Forgetful in daily activities

  7. DSM-IV Criteria (cont.) • Impulsivity/hyperactivity - six or more of the following, manifested often: • Impulsivity: • Blurts out answers before question is finished • Difficulty awaiting turn • Interrupts or intrudes on others

  8. DSM-IV Criteria (cont.) • Hyperactivity: • Fidgets with hands or feet • Unable to stay seated, squirms in seat • Inappropriate running/climbing (restlessness) • Difficulty in engaging in leisure activities quietly • “On the go”, “driven by motor” • Talks excessively

  9. ADHD:DSM-IV Subtypes • ADHD Predominantly Inattentive Type • Criteria met for inattention, but not for impulsivity/hyperactivity • ADHD Predominantly Hyperactive-Impulsive Type Criteria met for impulsivity/hyperactivity, but not for inattention • ADHD Combined Type Criteria are met for both inattention and impulsivity/hyperactivity

  10. DSM-IV Adult Criteria • Three critical elements: • Childhood onset • Presence of significant symptoms • Impairment from these symptoms in at least two domains: school/work, social interaction, or home life APA, 1994

  11. Clinical Presentation • Patients may complain of • Procrastination, being unwilling to wait in lines, speeding while driving, overreaction to frustration, poor motivation, difficulties with time management leading to social and occupational impairments. • Research has shown • Lower occupational achievements, higher rates of separation or divorce, higher rates of driving violations, frequent job changes, increased social maladjustments, increased immaturity. Weiss & Weiss, 2004

  12. Comorbid Conditions in Adults with ADHD • Antisocial disorders (such as conduct disorder, oppositional defiant disorder, antisocial personality disorder) • Mood and anxiety disorders • Substance abuse and dependence Biederman, 2004

  13. ADHD symptoms in epilepsy • Impulsivity • Poor frustration tolerance • Distractibility and short attention span • Restlessness • Interictal ADHD may be indistinguishable from ADHD in non-epilepsy patients. • Occurring only as pre-ictal symptoms (8 to 72 hours prior to seizure occurrence) • Occurring as postictal symptoms (within 120 hours of seizures. • Often pre-ictal symptoms persist into the postictal period. • Interictal symptoms may often worsen during preictal and postictal periods.

  14. Molecular Genetics of ADHD • Studies of children with ADHD show abnormalities in • D2 dopamine receptor gene • Dopamine-beta-hydroxylase gene • Dopamine transporter gene (DAT) on chromosome 5 • D4 dopamine receptor gene on chromosome 11 • DRD4 7-repeat allele implicated in novelty seeking • Mediates blunted response to dopamine • Location of most D4 receptors - frontal lobes Faraone et al., 2000

  15. Family Studies In non-epilepsy patients: • 57% prevalence of ADHD in children of ADHD adults. • ADHD in first-degree family member of children with ADHD range from 20 to 25% In epilepsy patients: ?

  16. Neuropsychological Studies of ADHD • Studies in adults show: • Impairment in measures of attention • Impairment on measures of executive functioning (vigilance, perceptual-motor speed, working memory, response inhibition, written arithmetic) and memory (verbal learning and semantic encoding). • In epilepsy patients, cognitive disturbances may be related to the type of epilepsy, location of seizure focus and underlying brain damage.

  17. Type of epilepsy syndromes associated with Adult ADHD • Partial epilepsies • Temporal lobe epilepsy • Frontal lobe epilepsy • Occipital lobe epilepsy • Primary Generalized epilepsy • Juvenile Myoclonic epilepsy • Secondary Generalized epilepsy

  18. Neuroimaging Studies of ADHD In non-epilepsy patients • Functional studies in adults primarily implicate frontal and striatal brain regions: • PET study with F18-DOPA showed significantly lower ratios in prefrontal cortex. Ernst et al.,1998 • DAT activity in striatum elevated by 70% compared to controls. Dougherty et al.,1999 In epilepsy patients • MRI and PET abnormalities related to underlying seizure disorder.

  19. Rating Scales for ADHD Symptoms in Adults • Self Report and/or informant • Symptom checklist and/or severity measures • Often developed for childhood ADHD and then modified for adults • Varying reliability and validity

  20. Conners' Adult ADHD Rating Scales • Assessed Domains • Inattention/Memory Problems • Impulsivity/Emotional Liability • Hyperactivity/Restlessness • Problems with Self-Concept • ADHD DSM-IV Symptoms • ADHD index • Internal consistency of responses • Informant and Self Report forms • 15 minutes to complete • Vendor - Pearson Assessment

  21. Overview of Rating Scales for ADHD Symptoms in Adults • Conners’ Adult ADHD Rating Scales • ADHD Rating Scale – IV • Adult ADHD Self-Report Scale • Brown ADD Rating Scale for Adults • Current Symptoms Scale • Wender-Utah Rating Scale

  22. CAUTION:Adult ADHD Rating Scales Have yet to be validated in patients with epilepsy!!

  23. Iatrogenic ADHD in Adults with Epilepsy • Symptoms of ADHD can be caused or worsened by: • Any AED at toxic doses • Phenobarbital • Primidone • Benzodiazepines • Vigabatrine • Topiramate • Levetiracetam • Zonisamide

  24. Treatment of ADHD in Adults with Epilepsy General Principles • Before making a diagnosis of ADD, rule out: • an iatrogenic cause • A learning disability that can mimic short attention span (i.e., auditory verbal processing disturbance).

  25. Treatment of ADHD in Adults with Epilepsy • Pharmacotherapy: • CNS stimulants • Atomoxetine • Antidepressant medication • Psychotherapy: • Only cognitive therapy helpful.

  26. Pharmacotherapy of ADHD in Adults with Epilepsy: CNS Stimulants • Safe in patients with epilepsy • Methylphenidate (MPH) - Immediate release (Ritalin) - Extended release (Concerta) • Its clearance is not affected by AEDs. • Amphetamine compounds: - Dextroamphetamine (Adderal; immediate and extended release) • Magnesium pemoline (Cylert) • The clearance of amphetamines and magnesium pemoline is increased by enzyme inducing AEDs.

  27. Pharmacotherapy of ADHD in Adults with Epilepsy: CNS Stimulants: Adverse events • Adverse events is dose-related • Insomnia • Headache • Decreased appetite • Nausea • Weight loss • Nervousness • Tics • Increase in BP • Increase in heart rate • Magnesium pemoline has been associated with liver failure.

  28. Pharmacotherapy of ADHD in Adults with Epilepsy: Antidepressants • Tricyclics • Imipramine (Tofranil) • Desipramine (Norpramine) • Start a low doses (25 mg/day) and increase slowly until desired effect is obtained or a maximal dose of 300 mg/day is reached. • Get EKG at baseline and after reaching target dose. • Check serum concentrations of TCA to avoid toxic levels associated with worsening of seizures. • TCA levels will drop in the presence of enzyme inducing AEDs (phenytoin, carbamazepine, phenobarbital, primidone (and topiramate and oxcarbazepine at high doses) • Bupropion is an antidepressant drug that is effective in the treatment of ADHD but should not be used in patients with epilepsy

  29. Factors associated with antidepressant induced seizure occurrencein non-epilepsy patients • Rapid dose titration • High serum concentrations • Concomitant drugs that lower the seizure threshold. • CNS pathology • Abnormal EEG • Family history of epilepsy

  30. Pharmacotherapy of ADHD in Adults with Epilepsy: Atomoxetine (Strattera) • Noradrenergic agent • Efficacy in adults with ADHD established in double-blind-placebo controlled study. • N = 536 adults • Target dose: 120 mg/day (90 mg/day preferred) • 10-week study • Significant differences noted since week 2 • Dose schedule: Start at 0.5 mg/kg/day x 2weeks, then 1.2 mg/kg/day. If necessary, increase dose after six weeks to 1.4 mg/kg/day and up to 1.8 mg/kg/day. • Safety with respect to seizure occurrence? • No evidence of lowering of seizure threshold up to the present time.

  31. Pharmacotherapy of ADHD in Adults with Epilepsy: Atomoxetine: Adverse events • Dry mouth • Insomnia • Nausea • Decreased appetite • Decreased libido • Erectile difficulty • Dizziness • Increase in BP: 1 to 3 mm in diastolic and systolic pressures • Increase in heart rate: 5 bpm.

  32. Conclusions: • ADD is an unrecognized and under-treated neuropsychiatric comorbidity in adults with epilepsy. • They are likely to occur in patients with partial epilepsy of temporal and frontal lobe origin as well as in patients with primary generalized epilepsy. • The actual prevalence of ADD in adults with epilepsy is yet to be established. • Iatrogenic cause must always be ruled-out before considering a trial with pharmacotherapy. • The treatment is identical to that of ADD patients without epilepsy.

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