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 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 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 encourage a philosophy of treating the whole person within their daily context. To present research about adults who were treated for ADHD as children. 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 Parents who do not understand, are frustrated and feel guilty Teachers who may label a child as lazy, slow, bad, or lacking motivation. Teachers who may label a child as lazy, slow, bad, or lacking motivation. Rejection by peers because of poor social skills. Rejection by peers because of poor social skills. Spouse or boss who are exasperated by lack of organization, forgetfulness, and inability to complete tasks. Spouse or boss who are exasperated by lack of organization, forgetfulness, and inability to complete tasks. Risks of co morbid conditions Risks of co morbid conditions

Medications for ADHD  Psychostimulants Methylphenidate based (Ritalin) Methylphenidate based (Ritalin) Dexamphetamine based (Dexedrine) Dexamphetamine based (Dexedrine)  Non-stimulants Atomoxetine (Strattera) Atomoxetine (Strattera) Guanfacine (Tenex) Guanfacine (Tenex)  Antidepressants Buproprion (Wellbutrin) 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 UnacceptableUnacceptable Personality Change or social withdrawalPersonality Change or social withdrawal Labile mood/irritabilityLabile mood/irritability Excessive Lethargy (Zombie)Excessive Lethargy (Zombie) Liver Injury (Strattera)Liver Injury (Strattera) Mania (caution should be taken in treating individuals with Bipolar disorder)Mania (caution should be taken in treating individuals with Bipolar disorder) Psychosis rarely may develop in individuals with no prior historyPsychosis rarely may develop in individuals with no prior history

ADHD Medication Side Effects Possibly ManageablePossibly Manageable TicsTics SeizuresSeizures Family history of heart diseaseFamily history of heart disease

Rebound from ADHD Medication Irritability, hyperactivity and impulsiveness exceeding untreated symptoms Irritability, hyperactivity and impulsiveness exceeding untreated symptoms Related to psychostimulants “wearing off” Related to psychostimulants “wearing off” Often coincides with homework time Often coincides with homework time Increases family stress Increases family stress May suggest need for increased dose or change of medication May suggest need for increased dose or change of medication Often requires short acting stimulant supplement Often requires short acting stimulant supplement

Black Box Warnings  Stimulants Risk of sudden death Risk of sudden death 25 deaths and 54 cardiovascular problems in adults and children between 1999 and deaths and 54 cardiovascular problems in adults and children between 1999 and 2003 Report does not indicate the drugs were responsible for the deaths Report does not indicate the drugs were responsible for the deaths Screen all patients for high risk conditions including structural heart defects. Screen all patients for high risk conditions including structural heart defects.  Strattera Increased suicidal thoughts Increased suicidal thoughts No increase in suicide attempts No increase in suicide attempts Monitoring is recommended. Monitoring is recommended. Liver injury Liver injury

Psychostimulants  Methylphenidate products (Ritalin) Ritalin (4 hours average duration of effect) Ritalin (4 hours average duration of effect) Ritalin LA (8-10 hours) Ritalin LA (8-10 hours) Metadate CD (10 hours) Metadate CD (10 hours) Concerta (10-12 hours) Concerta (10-12 hours) Focalin (dexmethylphenidate) (4-6 hours) Focalin (dexmethylphenidate) (4-6 hours) Focalin XR (8-10 hours) Focalin XR (8-10 hours) Daytrana (methylphenidate transdermal system) (2-3hr. after patch removed) Daytrana (methylphenidate transdermal system) (2-3hr. after patch removed)

Psychostimulants  Amphetamine products Dextrostat (4-5 hours) Dextrostat (4-5 hours) Mixed amphetamine salts Mixed amphetamine salts Adderall (4-6 hours)Adderall (4-6 hours) Adderall XR (10-12 hours)Adderall XR (10-12 hours) Lisdexamfetamine (Vyvanse) Lisdexamfetamine (Vyvanse) hours11-13 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 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 Family history of response to medication Prioritized “Target Symptoms” Prioritized “Target Symptoms” Compliance and Follow-up requirements Compliance and Follow-up requirements Plan for coordination of care (counselors, teachers, care providers, parents) 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 with stimulants does not increase substance abuse Effective management of ADHD significantly decreases risk for 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 have greater absenteeism from work Parents of children with ADHD are less productive in the work place 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 Marriage/divorce- 3-5 times greater parental divorce or separation in families with a child with ADHD Possibly related to untreated ADHD in parentPossibly 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 successVocational 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, co- morbid 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 Child’s profile- affinities, personality traits, social skills, emotional stability Anxiety or depression symptoms Anxiety or depression symptoms Aggressive behavior Aggressive behavior Other medical diagnosis Other medical diagnosis Sleep patterns Sleep patterns Tics Tics Seizures Seizures Family dynamics Family dynamics

Choosing ADHD Medications Morning person (runs out of mental energy in afternoon) Morning person (runs out of mental energy in afternoon) Avoid difficult classes in afternoonAvoid difficult classes in afternoon Encourage afternoon physical activityEncourage afternoon physical activity Homework may require supplemental medication after schoolHomework may require supplemental medication after school Rebound symptoms may be more likely without supplemental medicationRebound symptoms may be more likely without supplemental medication Consider Concerta, Metadate CD, Adderall XR, Daytrana, Vyvanse, StratteraConsider Concerta, Metadate CD, Adderall XR, Daytrana, Vyvanse, Strattera

Choosing ADHD Medications Afternoon person (hard to get started in morning) Afternoon person (hard to get started in morning) Schedule difficult classes in mid daySchedule difficult classes in mid day Encourage morning physical activityEncourage morning physical activity Evaluate sleep hygiene at each visitEvaluate sleep hygiene at each visit May require short acting stimulant in morning in addition to sustained release preparationMay require short acting stimulant in morning in addition to sustained release preparation Consider Ritalin LA, Focalin XR, Vyvanse, StratteraConsider 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 less effective for hyperactivity Strattera can be used in conjunction with stimulants 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 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 Child with ADHD has parent with undiagnosed/untreated ADHD Lack of family and patient education about ADHD Lack of family and patient education about ADHD Failure to consistently follow management plan Failure to consistently follow management plan Undiagnosed co morbid condition Undiagnosed co morbid condition Lack of recognition for success Lack of recognition for success 80% of interactions for children with ADHD who are not stabilized are negative.80% of interactions for children with ADHD who are not stabilized are negative. Reinforce the positive. Catch them doing well.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

 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 (2- 3 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 greater awareness of symptoms and impairments Have higher education, salaries, higher SES, higher IQ’s Have higher education, salaries, higher SES, higher IQ’s Less antisocial, less drug use Less antisocial, less drug use More co morbid depression, anxiety More co morbid depression, anxiety Impaired executive functions (sustained attention, task completion) Impaired executive functions (sustained attention, task completion) Similar impairments in risky sexual behavior, marriage, child rearing, money management, driving and health care 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 minutes with peak at 1 hour and duration average of 4 hours

Ritalin LA Available as 10 mg., 20 mg., 30 mg. Available as 10 mg., 20 mg., 30 mg. Bead filled capsule that can be swallowed or sprinkled on applesauce 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) 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 Onset within 1 hour and peak serum levels at 3 and 6 hours after ingestion Absorption affected by food, especially fatty meals slowing absorption 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 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 min with initial peak at 1 hour and secondary peak at 6-10 hours and duration of hours  Absorption unaffected by food

Focalin XR (dexmethylphenidate)  Extended release formulation Available as 5 mg, 10 mg, 15 mg, and 20 mg Available as 5 mg, 10 mg, 15 mg, and 20 mg Bead filled capsule that can be swallowed or sprinkled on applesauce 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) 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 Onset within 1 hour and peak serum levels at 3 and 6 hours after ingestion Absorption effected by food, especially fatty meals slowing absorption Absorption effected by food, especially fatty meals slowing absorption Duration of effect 8-10 hours 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 Single isomer active ingredient Inactive isomer (levomethylphenidate) may: Inactive isomer (levomethylphenidate) may: Block receptor siteBlock receptor site Cause side effectsCause 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.  NE has wide, diffuse projections throughout the brain suggesting a role as a neuromodulator.  NE is critical to  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 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 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 History, physical, neurological examination, fine and gross motor assessment Neurodevelopmental assessment Neurodevelopmental assessment Vision and hearing screening Vision and hearing screening  Emotional History and interview History and interview  Family-Environmental Family/School milieus and extracurricular activities Family/School milieus and extracurricular activities Family mental health history Family mental health history

Assessment of Specific Components of Attention and Behavior  Rating scales Parents, teachers, self report Parents, teachers, self report  Interviews Parent, patient Parent, patient  Direct observations Classroom Classroom During testing During testing  Objective measures Computerized (controversial) Computerized (controversial)

Evaluation of Cognitive and Academic Function  Processing abilities Verbal/language, visual, sequential 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