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Raising the Bar 2008 Medication for ADHD Presentation to Families with ADHD Frank W. Gearing, MD Harrisonburg Pediatrics March 20, 2008 Medication for ADHD Goals for this presentation: To leave the participant aware of the complexity of successful management of ADHD. To familiarize the participant with medication options and some rationale to therapy decisions. To encourage a philosophy of treating the whole person within their daily context. To present research about adults who were treated for ADHD as children. Principles of Management of ADHD Medications Correct diagnosis Patient profile Target symptoms Chronic disease management model of care Education of key players Communication Principles of Management of ADHD Selection of an appropriate medication at an appropriate dose in combination with behavioral therapy are the foundation of therapy. Adequate behavioral therapy involves intensive and prolonged parent involvement and cooperation from the teacher. All children with ADHD should be evaluated for LD and treatment of LD, when present, should be included in management. Individuals with ADHD should get enough to eat, get enough sleep, and have sufficient exercise. Why Treat ADHD Individuals with ADHD are impacted over a lifetime by: Parents who do not understand, are frustrated and feel guilty Teachers who may label a child as lazy, slow, bad, or lacking motivation. Rejection by peers because of poor social skills. Spouse or boss who are exasperated by lack of organization, forgetfulness, and inability to complete tasks. Risks of co morbid conditions Medications for ADHD Psychostimulants Methylphenidate based (Ritalin) Dexamphetamine based (Dexedrine) Non-stimulants Atomoxetine (Strattera) Guanfacine (Tenex) Antidepressants Buproprion (Wellbutrin) ADHD Medication Benefits Improve selective and sustained attention Improve impulse control Improve regulation of activity and arousal Improve memory Improve productivity, accuracy, and organization Improve reinforceability Improve emotional control ADHD Medication Side Effects Manageable Decreased appetite Headache Stomachache Insomnia Suicidal thoughts (Strattera) Skin rash (Daytrana) ADHD Medication Side Effects • Unacceptable • Personality Change or social withdrawal • Labile mood/irritability • Excessive Lethargy (Zombie) • Liver Injury (Strattera) • Mania (caution should be taken in treating individuals with Bipolar disorder) • Psychosis rarely may develop in individuals with no prior history ADHD Medication Side Effects • Possibly Manageable • Tics • Seizures • Family history of heart disease Rebound from ADHD Medication Irritability, hyperactivity and impulsiveness exceeding untreated symptoms Related to psychostimulants “wearing off” Often coincides with homework time Increases family stress May suggest need for increased dose or change of medication Often requires short acting stimulant supplement Black Box Warnings Stimulants Risk of sudden death 25 deaths and 54 cardiovascular problems in adults and children between 1999 and 2003 Report does not indicate the drugs were responsible for the deaths Screen all patients for high risk conditions including structural heart defects. Strattera Increased suicidal thoughts No increase in suicide attempts Monitoring is recommended. Liver injury Psychostimulants Methylphenidate products (Ritalin) Ritalin (4 hours average duration of effect) Ritalin LA (8-10 hours) Metadate CD (10 hours) Concerta (10-12 hours) Focalin (dexmethylphenidate) (4-6 hours) Focalin XR (8-10 hours) Daytrana (methylphenidate transdermal system) (2-3hr. after patch removed) Psychostimulants Amphetamine products Dextrostat (4-5 hours) Mixed amphetamine salts • Adderall (4-6 hours) • Adderall XR (10-12 hours) Lisdexamfetamine (Vyvanse) • 11-13 hours Vyvanse (lisdexamphetamine) Prodrug that must be metabolized to active ingredient (single dextro isomer of amphetamine) Available as 30 mg, 50 mg, 70 mg No generic FDA has approved 20 mg, 40 mg, 60 mg that are not available at this time Onset in 1-2 hours and reaches peak at 3.5 hours with duration of 11-13 hours Food prolongs time to peak concentration Non Stimulant Medications Strattera (atomoxetine) Tenex (guanfacine) Wellbutrin (buproprion) Strattera (atomoxetine) Strattera is a selective norepinephrine reuptake inhibitor It is not recommended but it is known to be stable when capsule contents dissolved in grape juice for those unable to swallow capsule Absorption unaffected by food Tenex (guanfacine) Tenex is an antihypertensive (alpha adrenergic) medication that has been used to treat hyperactive-impulsive and aggressive behaviors in individuals with ADHD. Tenex has been used for insomnia in ADHD patients and to suppress Tics in Tourettes patients Recent research has shown that with continued use, inattention shows continuous improvement A sustained release and a patch are currently in clinical trials with the sustained release showing greater benefit and flexibility than the immediate release formulation Wellbutrin (buproprion) Wellbutrin is an atypical antidepressant that is a dopamine and norepinephrine reuptake inhibitor that has been shown to be effective for ADHD Wellbutrin has been advocated in ADHD patients with substance abuse disorder Zyban is also buproprion marketed under another name as a smoking cessation aid. It is recommended for ADHD with unstable mood disorder, and seasonal affective disorder. Management of ADHD Prior to initiating medication document: Family history of response to medication Prioritized “Target Symptoms” Compliance and Follow-up requirements Plan for coordination of care (counselors, teachers, care providers, parents) Monitoring ADHD Medications Monthly weight, height, and blood pressure until on stable dose followed by routine 3 month interval checks Appetite, sleep, energy, mood changes, academic performance, behavior concerns, social relations, family relations Worries, rituals, depression, thoughts of suicide Be specific and detailed (number of hours of sleep/night, specific grades per subject, extracurricular activities, etc.) Risks of Not Treating ADHD Untreated ADHD has twice the risk for substance abuse, with earlier onset, and less likelihood to recover as an adult Effective management of ADHD with stimulants does not increase substance abuse Effective management of ADHD significantly decreases risk for substance abuse Risks of Not Treating ADHD Employment stability Parents of children with ADHD have greater absenteeism from work Parents of children with ADHD are less productive in the work place Interpersonal relationships Marriage/divorce- 3-5 times greater parental divorce or separation in families with a child with ADHD • Possibly related to untreated ADHD in parent Untreated adults with ADHD have poor employment records • Vocational aptitude testing beneficial for teens with ADHD seeking areas of likely success ADHD Treatment of Preschool Children Preschool children have higher incidence of side effects from stimulants, especially abdominal pain, decreased appetite, and insomnia, but recent PATS study shows stimulants clearly of benefit Factors associated with lower response to stimulants include lower IQ, greater severity of symptoms, comorbid conditions, family dysfunction, confidence in diagnosis Preliminary evidence of efficacy of Tenex without side effects of stimulants and greater hyperactive/impulsive symptoms may suggest Tenex a better first medication trial, along with behavioral interventions Most frequent co morbid condition was ODD, followed by communication/language disorder and anxiety Choosing ADHD Medication Consider Child’s profile- affinities, personality traits, social skills, emotional stability Anxiety or depression symptoms Aggressive behavior Other medical diagnosis Sleep patterns Tics Seizures Family dynamics Choosing ADHD Medications Morning person (runs out of mental energy in afternoon) • Avoid difficult classes in afternoon • Encourage afternoon physical activity • Homework may require supplemental medication after school • Rebound symptoms may be more likely without supplemental medication • Consider Concerta, Metadate CD, Adderall XR, Daytrana, Vyvanse, Strattera Choosing ADHD Medications Afternoon person (hard to get started in morning) • Schedule difficult classes in mid day • Encourage morning physical activity • Evaluate sleep hygiene at each visit • May require short acting stimulant in morning in addition to sustained release preparation • Consider Ritalin LA, Focalin XR, Vyvanse, Strattera Choosing ADHD Medication ADHD with depressive or anxious symptoms may respond best to Strattera Strattera less effective for hyperactivity Strattera can be used in conjunction with stimulants SSRI’s are well tolerated and can be used in conjunction with stimulants for more depressed or anxious patients Aggressive behaviors, tics, and disturbed sleep may respond to Clonidine or Guanfacine Controversy about safety of stimulants with Clonidine Insomnia may respond to Melatonin Medications for ADHD Reasons for treatment failure Child with ADHD has parent with undiagnosed/untreated ADHD Lack of family and patient education about ADHD Failure to consistently follow management plan Undiagnosed co morbid condition Lack of recognition for success • 80% of interactions for children with ADHD who are not stabilized are negative. • Reinforce the positive. Catch them doing well. Medications for ADHD When there is a sudden deterioration in daily functioning after a long period of stability it is most often not an issue of medication failure. Consider other explanations such as changes in family dynamics, changes in peer relations, pregnancy, drug use, etc. ADHD in Adults ADHD in Adults 80-90% of individuals diagnosed and treated as children for ADHD have areas of impairment as adults. Education: higher drop out rate, lower GPA, fewer college graduates Employment: unskilled level jobs, greater periods of unemployment, higher likelihood of being fired, lower work performance ratings, lower job status ADHD in Adults Poorer driving skills More auto accidents with more at faults (23 times risk) Worse accidents (3 times more cost and injuries) More citations (speeding 4-5 times risk) 3 times more license suspensions Alcohol has greater adverse impact on driving ADHD in Adults Begin sexual activity earlier More lifetime sexual partners with less time per partner Higher risks for STDs Less likely to use contraception 6-7 times more teen pregnancies 54% do not have custody of their children ADHD in Adults Higher incidence of co morbid disorders (anxiety, substance use/abuse, personality disorders, depression, suicide attempts) Greater frequency of antisocial acts: stealing, assault, illegal drug possession, breaking and entering, setting fires, runaway Fewer close friends Watch more TV, play more video games Less time reading, exercising, getting education More sleep disturbances ADHD in Adults Higher incidence of medical and dental problems Money management problems Greater likelihood of smoking and excess alcohol use Higher risk of cardiovascular disease ? Greater risk of cancer ADHD in Adults Adults not diagnosed with ADHD as children who present with ADHD: Have greater awareness of symptoms and impairments Have higher education, salaries, higher SES, higher IQ’s Less antisocial, less drug use More co morbid depression, anxiety Impaired executive functions (sustained attention, task completion) Similar impairments in risky sexual behavior, marriage, child rearing, money management, driving and health care Treatment of ADHD in Adults Adults often respond well to Strattera. Wellbutrin and Effexor are used more frequently in adults than children for ADHD Caution is required to address preexisting health conditions and use of other medication in adults. Counseling is important for improving self awareness and addressing co morbid conditions. Accommodations can often be implemented with the cooperation of employers, spouses, and coworkers. The medications we discussed in this presentation are used in adults as well as children. Summary Children with ADHD need to understand themselves to work toward independence. Compliance with routine should be closely monitored with associated consequences. Teacher involvement is crucial to include daily communication with the focus on making the child responsible, and teaching the child to monitor his own work. Training these behaviors takes a long time and a lot of persistence on the part of parents. Summary ADHD is a complex disorder beginning in childhood that may impact as many as 90% of affected children as they grow to adulthood. Severe symptoms of ADHD in childhood are associated with risk of impairment in academics, social relations, family relations, work success, and healthy lifestyle choices. Effective management involves a closely monitored, comprehensive approach that involves physicians, counselors, teachers, and especially parents. As affected individuals age, spouses, bosses, counselors, and friends will be part of successful management. Medication is a major component of managing ADHD in children and adults. Summary Recognition and treatment of co morbid conditions, especially learning disorders in children and mood disorders in adults is crucial to success. Attention to diet, sleep, exercise and establishing routines are points of emphasis. Building on the strengths identified in the individuals profile while working to improve areas in need of improvement will be important goals for the individual as they grow in their own self awareness. Addendum Medications for ADHD Methylphenidate products Effects attributed to blocking Dopamine (DA) reuptake at the neuron synapse DA is involved in frontal and prefrontal cortex mediating suppression of distractions and inhibiting inappropriate behaviors related to tangential thoughts and ideas (mesocortex pathway). DA is involved in mediating working memory required for reasoning, planning, and problem solving (mesodorsolateral pathway). DA is involved in mediating interpersonal decisions and inhibiting impulsive social responses. Ritalin (methylphenidate) Available as tablet 5 mg, 10 mg, 20 mg Available as liquid 10 mg/5 ml Available as generic Onset within 30-60 minutes with peak at 1 hour and duration average of 4 hours Ritalin LA Available as 10 mg., 20 mg., 30 mg. Bead filled capsule that can be swallowed or sprinkled on applesauce Uses SODAS absorption technology and replicates twice daily dosing 4 hours apart of equal amounts of methylphenidate (50-50) Onset within 1 hour and peak serum levels at 3 and 6 hours after ingestion Absorption affected by food, especially fatty meals slowing absorption Metadate CD Extended release formulation of methylphenidate Available as 10 mg, 20 mg, 30 mg bead filled capsule that can be sprinkled on apple sauce No generic 30% of dose available as immediate release with onset in 30-60 minutes and 70% of dose extended slow release Dual peak concentrations at 1.5 hours and 4.5 hours that are delayed by fatty meals Duration of effect 8-10 hours Concerta Available as 18 mg, 27 mg, 36 mg, 54mg tablet No generic Exterior coating of tablet dissolves in water and provides immediate release of 22% of dose Uses OROS technology for osmotic release of 78% of dose in slow consistent manner over 5-9 hours Onset of immediate release within 30-60 min with initial peak at 1 hour and secondary peak at 6-10 hours and duration of 10-12 hours Absorption unaffected by food Focalin XR (dexmethylphenidate) Extended release formulation Available as 5 mg, 10 mg, 15 mg, and 20 mg Bead filled capsule that can be swallowed or sprinkled on applesauce Uses SODAS absorption technology and replicates twice daily dosing 4 hours apart of equal amounts of dexmethylphenidate (50-50) Onset within 1 hour and peak serum levels at 3 and 6 hours after ingestion Absorption effected by food, especially fatty meals slowing absorption Duration of effect 8-10 hours Focalin (dexmethylphenidate) Single isomer formulation of Ritalin Available as tablet 2.5 mg, 5 mg, 10 mg Available as generic Onset in 1 hour with peak at 3 hours and duration of effect of 4-6 hours Absorption slowed by food, especially fat Theory of single isomer Single isomer active ingredient Inactive isomer (levomethylphenidate) may: • Block receptor site • Cause side effects Dexedrine Products Dexedrine products increase levels of dopamine (DA) and norepinephrine(NE) at the synapse by stimulating release and blocking reuptake of the neurotransmitters NE has wide, diffuse projections throughout the brain suggesting a role as a neuromodulator. NE is critical to reasoning, learning, problem solving, priority setting, organizational thought NE functions in maintaining arousal, regulating excitability related to danger (fright/flight), contributes to memory storage and retrieval DA is involved in suppressing distractions, inhibiting inappropriate behavior, reasoning, planning, problem solving, inhibiting impulsive social responses. Dextrostat (dextroamphetamine) Single d-isomer of amphetamine Available as 5 mg, 10 mg scored tablets Approved from age 3 years Peak level at 2 hours Dose recommendation of once daily Adderall (mixed amphetamine salts) d,l amphetamine sulfate, dextroamphetamine saccharate, d,l amphetamine aspartate Available as 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, 30 mg Generic available Duration of effect 4-6 hours Adderall XR Two different beads in each capsule to give double pulsed delivery of medication Available as 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg. No generic Peak serum levels at 7 hours Fatty meal prolongs the time to peak levels Contents of capsule can be opened and spread on apple sauce Strattera Onset of benefit in 1-2 weeks with maximal benefit reached in 4-6 weeks Not recommended for crisis intervention Initial dosing recommended at 0.5 mg/kg for 3-5 days with gradual increase to FDA recommended dose of 1.2-1.4 mg/kg Dose can be split BID to avoid side effects Literature supports continued benefits for select patients with dose up to 1.8 mg/kg Warnings related to suicide ideation and liver toxicity Strattera Side effect profile includes headache, nausea, stomachache, decreased appetite, drowsiness, aggression, priapism, mania, psychosis Adult trials have reported erectile dysfunction, urinary retention, dysmenorrhea, hot flush Dosage adjustment may be needed when used in conjunction with SSRI Sudden death has been reported in individuals with underlying structural heart disease or other serious heart disease (not felt to be related to drug) Caution when treating co morbid Bipolar disorder Tenex Often used in conjunction with stimulants Discontinuation should be tapered to avoid blood pressure changes Side effects: somnolence, initial decrease in blood pressure, depression, rebound hypertension Catapres (clonidine) is a similar antihypertensive that has been used for similar reasons in ADHD but has significantly more sedation than Tenex Wellbutrin Side effects: agitation/activation, irritability, aggression, insomnia, suicidal ideation, panic attacks, anorexia, dry mouth, stomachache Contraindicated in individuals with seizures, and for use with Tagamet Onset of benefit in 10-14 days with maximal benefit at 3-6 weeks Often used in conjunction with stimulants Addendum Evaluation for ADHD Correct Diagnosis and Patient Profile Presenting problems Comprehensive evaluation Assessment of specific components of attention and behavior Evaluation of cognitive and academic functioning Assessment of secondary vulnerabilities Presenting Problems Poor Concentration Inattention/Distractibility Impulsivity Hyperactivity Academic problems Behavior problems Does this child have an attention disorder? Or associated disorders? What are this individual’s strengths and weaknesses? Comprehensive Evaluation Medical History, physical, neurological examination, fine and gross motor assessment Neurodevelopmental assessment Vision and hearing screening Emotional History and interview Family-Environmental Family/School milieus and extracurricular activities Family mental health history Assessment of Specific Components of Attention and Behavior Rating scales Parents, teachers, self report Interviews Parent, patient Direct observations Classroom During testing Objective measures Computerized (controversial) Evaluation of Cognitive and Academic Function Processing abilities Verbal/language, visual, sequential Memory Fine motor abilities, especially graphomotor skills Problems solving abilities Intelligence Academic achievement Assessment of Secondary Vulnerabilities Self esteem Social abilities Family interactions Classroom behaviors