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Basic Principles in the Pharmacologic Management of ADHD

Approved by: Robert P. Chayer, MD  
March 2013

Overview

  • Therapy may be indicated in ADHD to address organizational skills deficits or oppositional behavior. Nonetheless, medication is a first line treatment for ADHD. It is appropriate to start with either of the two stimulant classes (methylphenidate or amphetamine) or with atomoxetine. Stimulants have been shown to be effective more often than atomoxetine. The decision regarding which medication to start and when to start will need to be made as part of an informed consent discussion with the patient and parent/guardian.
  • A routine physical exam, including blood pressure, pulse, height and weight, should be performed prior to initiating stimulants. Vital signs should then be checked at each visit for potential tachycardia or hypertension. Obtaining a lead level should be considered for exposed children, but is not part of routine assessment.
    If the child doesn’t respond to the first stimulant tried (at maximum dosage) or has prohibitive side effects, try using another stimulant type or another medication class. 
  • “Rebound” in symptoms of ADHD is common in the late afternoon as the stimulant wears off, even with the sustained-release formulations. An immediate release dose may be given late in the afternoon to help avoid this phenomenon. Watch for sleep disturbances when the stimulants are given later in the day.
    The American Academy of Child and Adolescent Psychiatry (AACAP) Practice Parameters for ADHD (http://www.aacap.org/galleries/PracticeParameters/JAACAP_ADHD_2007.pdf) note the following contraindications to the use of stimulants: glaucoma, symptomatic cardiovascular disease, hyperthyroidism, hypertension, active psychosis, and concomitant use of an MAO-I (monoamine oxidase inhibitor). Caution should be exercised when there is a history of substance abuse in the home. In this case Atomoxetine or Vyvanse might be considered. Baseline EKG’s are not recommended for otherwise healthy individuals (see N.B. “2)” below).
  • The Food and Drug Administration has added other contraindications including motor tics, severe anxiety, and a family history or diagnosis of Tourette’s Disorder, although these are relative contraindications and these conditions may not be worsened by stimulants. In the presence of seizure disorder, it is best to initiate stimulant treatment following adequate seizure control with anticonvulsants.
    Consider referring to a child psychiatrist if two adequate trials of stimulants or Strattera have failed.

Treatment

Methylphenidate

  • For immediate release methylphenidate (e.g., Ritalin, etc.), begin with 2.5 mg (6 y.o.) twice daily (about 4 hours apart). Reassess for effectiveness and side effects (in person or by phone, as appropriate) every 1-2 weeks. If symptoms remain, continue to increase methylphenidate by 2.5-5 mg twice daily every 1-2 weeks until symptoms have resolved and impairment has been diminished. Maximum recommended dose is 1.5 mg/kg/d, up to 60 mg/day. Usually a longer duration of action is preferable; therefore it is common to add a third dose after school to help with homework and social activities. Alternately, start with or change to a sustained release formulation (Concerta, Metadate CD, Metadate ER, Methylin ER, or Ritalin LA). Ritalin LA and Metadate CD can be sprinkled. Focalin is the d-enantiomer of methylphenidate and requires half the dose up to a recommended maximum of 20mg/day. Focalin XR can be sprinkled.
  • The Daytrana patch is a formulation for methylphenidate. The starting dose is generally 1/3 to ½ of the oral methylphenidate dose (maximum dose 30mg/patch/day). Allow 15 hours before the next application. The patch should be applied to the hip at least two hours before the desired effect. Be sure to alternate hips with each new application and avoid the waistline. The patch can be worn up to 9 hours. Once removed it will continue to have effects for about three hours. Keep in mind that it needs to be worn at least 4 hours to get the additional three hours of efficacy after removal. The benefit to this preparation is the flexibility of the wear time. Watch for the possible side effect of allergic contact dermatitis. This should be suspected if erythema accompanied by edema, papules and/or vesicles appear and spread beyond the patch site.
  • Irritant contact dermatitis, primarily seen as erythema, tends to dissipate quickly and is generally not a concern.

Amphetamine

  • For mixed salts of amphetamine (Adderall), start at 2.5 mg (3-6 y.o.) or 5 mg (>6 y.o.) in the morning. Reassess every 1-2 weeks for effectiveness and side effects. Increase the dose in 2.5-5 mg intervals every 1-2 weeks until symptoms resolve, or to a maximum recommended dose of 1mg/kg or up to 40 mg/day. Increasing the dose of Adderall prolongs its duration of action. In addition, a second dose (4-6 hours after initial dose) or switching to Adderall XR (which can be sprinkled) can achieve a longer duration of action.
  • For dextroamphetamine (Dexedrine), start with 2.5 mg daily (3-6 y.o.) and 5 mg daily to twice daily (> 6 y.o.), given 4-5 hours apart. Reassess every 1-2 weeks for effectiveness and side effects. Increase the dose in 2.5-5 mg intervals until symptoms resolve. The maximum recommended dose is 1 mg/kg/day, up to 40mg daily. If a longer duration of action is needed, a third dose (half of the amount of the earlier doses) can be given. Alternately, change to Dexedrine Spansules. Vyvanse is a prodrug of dextroamphetamine and is an option if diversion is a concern. It is a therapeutically inactive molecule until after ingestion.
  • Vyvanse is converted to l-lysine and active damphetamine. It is still a scheduled medication and therefore one cannot write refills on the prescription. For pediatric patients starting treatment or switching from another medication the recommended dose is 30 mg once daily in the morning. At weekly intervals the dose may be titrated in 20 mg increments to a maximum recommended dose of 70 mg per day.

Other

  • Atomoxetine (Strattera) may be used as either first or second choice in the treatment of ADHD. Strattera would be a good choice to use first line in children with a history of stimulant or substance abuse, where there is a high potential for diversion, when control of symptoms in the evening is crucial, when anxiety or depression is co-morbid, or when requested by the patient/parents. Start at 0.5 mg/kg/d or lower, titrating up in increments every 2 weeks (while assessing for effectiveness and side effects) to a maximum recommended dose of 1.4 mg/kg/d. The FDA black box warning regarding suicidal ideation with antidepressants is also applicable to Strattera as noted (N.B.”3)”) below.
  • Long acting 2-agonists (Intuniv and Kapvay) have recently gained FDA-approval for use in ADHD. All forms of 2-agonists (clonidine, guanfacine) can be helpful in treating hyperactive/impulsive symptoms or (after initiation of stimulants) to treat tics, aggression, or sleep difficulties. 2-agonists are contraindicated if there is a history in the patient or first degree relatives of sudden death, repeated fainting episodes, or arrhythmia. The AACAP does not recommend a baseline EKG in otherwise healthy individuals. They must be tapered slowly when discontinuing due to the risk of rebound hypertension.
    • Clonidine (Catapres): Start with 0.05mg (1/2 tablet) bid (only qhs if treating sleep difficulties) and watch carefully for sleepiness or hypotension. Titrate slowly as needed to a maximum of the lesser of 0.01mg/kg/day or 0.4mg/day (or single dose maximum of 0.2mg).
    • Kapvay: Dosing should be initiated with one 0.1 mg tablet at bedtime, and the daily dosage should be adjusted in increments of 0.1 mg/day at weekly intervals until the desired response is achieved. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime.
    • Guanfacine (Tenex): Start with 0.5mg at night and titrate by 0.5mg in bid dosing to a maximum of the lesser of 0.1mg/kg or 4 mg.
    • Intuniv: Dose once daily. Tablets should not be crushed, chewed or broken before swallowing. Do not administer with high-fat meals, because of increased exposure. Do not substitute for immediate-release guanfacine, because of differing pharmacokinetics. If switching from immediate-release guanfacine, discontinue that treatment and begin at a dose of 1 mg once daily and adjust in increments of no more than 1mg/week. Maintain the dose within the range of 1 mg to 4 mg per day, depending on clinical response and tolerability. When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to7 days.

NB:

  1. Clonidine or Melatonin may be helpful in treating sleep difficulties related to stimulant use.
  2. The FDA issued a black box warning regarding the risk of sudden death on stimulants. The rate of sudden death in children on stimulants does not exceed the rate in the general population. There is no evidence to suggest the need for pre-treatment cardiac evaluation (such as EKG) in otherwise healthy individuals. Cardiac evaluation should be undertaken for children with a history of cardiac disease and those with symptoms suggestive of significant cardiac disease or if there is a family history of cardiac disease including but not limited to sudden cardiac death before the age of 50 years old, cardiomyopathy, arrhythmias or tachycardia.
    This recommendation is based on the most recent AACAP Practice Parameter which states:
    “This would include a history of severe palpitations, fainting, exercise intolerance not accounted for by obesity, or strong family history of sudden death. Postoperative tetralogy of Fallot, coronary artery abnormalities, and subaortic stenosis are known cardiac problems that require special considerations in using stimulants. Chest pain, arrhythmias, hypertension, or syncope may be signs of hypertrophic cardiomyopathy, which has been associated with sudden unexpected deaths in children and adolescents. Before a stimulant trial, such patients should be referred for consultation with a cardiologist for possible electrocardiography and/or echocardiography. If stimulants are initiated, then the patient should also be studied by the cardiologists during the course of treatment.”
  3. Selective Serotonin Reuptake Inhibitors (SSRI), Bupropion, and Atomoxetine (in cases of comorbid ADHD) are important medications in the treatment of pediatric depression and can be used safely. They do, however, require close supervision in the initial stages of treatment and at subsequent dosage alterations. The current recommendation by both the FDA and the American Academy of Child and Adolescent Psychiatry is that the patient ideally be monitored weekly for the first month (phone contact is okay), bi-weekly for the next month, and monthly thereafter. The FDA placed a “black box” warning on all antidepressants in October 2004 due to evidence of increased suicidal thinking in children and adolescents prescribed these medications. This was based on review of FDA clinical trials involving 4300 youth who received any of the currently available antidepressants. Analysis of the studies revealed a 4% risk of suicidal thinking for children on medication compared with 2% of those taking a placebo. A subsequent meta-analysis funded by the NIMH found a 3% risk of suicidal thinking for children on medication for depression compared with 2% of those taking placebo. No completed suicides occurred in any of these studies. For more information, please refer to www.parentsmedguide.org.

Children’s Hospital of Wisconsin, Inc. and the Child & Adolescent Psychiatry and Behavioral Medicine Center does not make any representation with respect to any sort of industry recognized standard of care for the particular subject matter of this/these document(s). Additionally, these documents are subject to change, revision, alteration and/or revocation without notice, depending on developments in the field. These are general recommendations from our psychiatrists.

Active Ingredient Medication Brand Name Dosing Duration of effect
Mixed salts of amphetamine  Adderall* tablets (scored): 5, 7.5, 10, 12.5, 15,
20, 30 mg 
Start with 2.5 (3 - 5yo) - 5 mg 1-2 times per day and increase by 5 mg every 1-2 weeks until good
control is achieved. MAX dose: lower of 1mg/kg/day or 40 mg/day 
4-8 hours
depending
on dose  
Adderall XR capsule (can be sprinkled): 5, 10,
15, 20, 25, 30 mg 
Start 5-10 mg in AM and increase by 5-10 mg every 1-2 weeks until good control is achieved.
Conversion: total daily dose of Adderall = am dose of Adderall XR. MAX dose: lower of 1mg/kg/day or
40 mg/day 
8-12 hours 
Dextroamphetamine  Dexedrine* tablet: 5, 10 mg Start with 5 mg 1-2 times per day and increase by 5 mg each week until good control is achieved.
MAX dose: lower of 1mg/kg/day or 40 mg/day 
Tablet: 4-5
hours 
Dexedrine Spansules* (can be sprinkled): 5, 10, 15 mg  Start at 5 mg in am and increase by 5 mg every 1-2 weeks until good control is achieved.
MAX dose: lower of 1mg/kg/day or 45 mg/day 
4-8 hours 
Vyvanse (can be dissolved in water): 20, 30,
40, 50, 60, 70mg 
Start at 30mg in am and increase by 20mg every week until good control is achieved. MAX dose:
70mg/day (Bound to lysine to decrease abuse potential) 
8-12 hours 
Methylphenidate  Concerta capsule (noncrushable): 18, 27, 36, 54 mg  Capsule cannot be split, so best to titrate with regular methlyphenidate and then switch to Concerta. 
Start at 18 mg in the a.m. and increase every 1-2 weeks until good control is achieved. Conversions:
Ritalin 5 mg tid = Concerta 18 mg, Ritalin 10 mg tid = Concerta 36 mg, Ritalin 15 mg tid = Concerta
54 mg. MAX dose: lower of 1.5mg/kg/day or 54 mg/day (child), 72 mg/day (adolescent) 
8-12 hours 
Focalin tablets (scored): 2.5, 5, 10 mg  Start with 2.5 mg 1-2 times per day and increase by 2.5 mg every 1-2 weeks until good control
achieved. May need 3rd reduced dose in PM. Conversion: half of total Ritalin daily dose = total
Focalin daily dose. MAX dose: lower of 0.8mg/kg/day or 20 mg/day 
3-4 hours 
Focalin XR (can be sprinkled): 5, 10, 15, 20, 30, 40 mg extended release  Start 5 mg in the am and increase dose by 5 mg every 1-2 weeks. Conversions: total daily dose of
Focalin = dose of Focalin XR in AM.; half of total Ritalin dose = Focalin XR dose in am. MAX dose:
lower of 0.8mg/kg/day or 20 mg/day 
8-12 hours 
Metadate ER tablets: 10, 20 mg extended release  Start at 10 mg in the am and increase by 10mg every 1-2 weeks until good control is achieved. May
need second Metadate ER dose or Ritalin dose in PM. MAX dose: lower of 1.5mg/kg/day or 60 gg y
mg/day 
4-8 hours 
Metadate CD capsule (may be sprinkled): 10, 20, 30 mg extended release  Start at 20 mg in the am and increase by 10-20 mg every 1-2 weeks until good control is achieved.
MAX dose: lower of 1.5mg/kg/day or 60 mg/day 
8-12 hours 
Methylin tablets (scored): 5, 10, 20; chewable 2.5, 5, 10; 5 mg/5 ml, 10 mg/5 ml solution  Start with 5 mg twice daily and increase by 5 mg every 1-2 weeks until good control is achieved. May
need 3rd reduced dose in PM. MAX dose: lower of 1.5mg/kg/day or 60 mg/day 
3-4 hours 
Methylin ER tablet: 10, 20 mg extended release  Start at 10 mg in the am and increase by 10 mg every 1-2 weeks until good control is achieved. May
need a dose of Ritalin in PM. MAX dose: lower of 1.5mg/kg/day or 60 mg/day 
4-8 hours 
Ritalin* tablets (scored): 5, 10, 20 mg   Start with 5 mg twice daily and increase by 5 mg every 1-2 weeks until good control is achieved. May
need 3rd reduced dose in PM. MAX dose: lower of 1.5mg/kg/day or 60 mg/day 
3-4 hours 
Ritalin* SR tablet: 20 mg Start at 20 mg in the am and increase by 20 mg every 1-2 weeks until good control is achieved. May need second dose of SR or Ritalin in PM. Conversions: total daily dose of Ritalin= AM dose of Ritalin SR. MAX dose: lower of 1.5mg/kg/day or 60 mg/day  4-8 hours 
Ritalin LA capsule (can be sprinkled): 10, 20, 30, 40 mg  Capsule cannot be split, so best to titrate with regular methlyphenidate and then switch to Ritalin LA.
Conversions: total daily dose of Ritalin = AM dose of Ritalin LA. MAX dose: lower of 1.5mg/kg/day or
60 mg/day 
8-12 hours 
Daytrana patch (worn on hip for 9 hours) 10mg,15mg, 20mg, 30mg  Apply the patch to a clean, dry area of the hip (avoid waistline) 2 hours before an effect is needed.
Increase by 5-10mg every 1-2 weeks until good control achieved. MAX dose: 30mg/day. DO NOT
apply heat onto patch or apply to inflamed skin. Change to po for rash. 
9-12 hours 
Atomoxetine  Strattera capsule: 10,18, 25,40, 60 mg  Start 10mg in the a.m.; titrate up every 2 weeks until good control is achieved. qD or bid. MAX dose: 1.4 mg/kg/day, up to 80mg/day. Useful for comorbid anxiety or depression and ADHD. FDA Black Box warning re suicidal ideation is applicable.
 
24 hours 
Bupropion  Wellbutrin SR: 100, 150 Not for young children. Start at 100 mg 1/2 tab qAM for 4-6 days (not scored), then 1 tab qAM. Titrate up by 50 mg/day each month until desired effect. MAX dose: lower of 6mg/kg or 400 mg/day. Useful for comorbid depression and ADHD. Contraindicated with history of seizures or eating disorder. FDA Black Box warning regarding suicidal ideation is applicable.  24 hours 
Alpha 2 agonist  Clonidine 0.1, 0.2 mg
Kapvay 0.1mg, 0.2 mg  
Clonidine: Start 0.05mg qhs to address sleep difficulties, 0.05 bid for tics, impulsivity or aggression and increase by 0.05mg/dose every 4 weeks until good control is achieved. Watch carefully for sleepiness or hypotension. Titrate slowly as needed to a maximum of the lesser of 0.01mg/kg/day or 0.4mg/day (or single dos maximum of 0.2mg)
Kapvay: start one 0.1 mg tablet at bedtime, and the daily dosage should be adjusted in increments of 0.1 mg.day at weekly intervals until the desired response is achieved. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime.

2-agonists are contraindicated if there is a history in the patient or first degree relatives of sudden death, repeated fainting episodes, or arrhythmia. AACAP does not recommend a baseline EKG in otherwise healthy individuals. They must be tapered slowly when discontinuing due to the risk of rebound hypertension.
 
Clonidine 6-10 hours; Kapvay 12-18 hours 
Guanfacine 1, 2mg
Intunive 1, 2, 3mg 
Guanfacine: Start with 0.5mg at night and titrate by 0.5mg in bid dosing to a maximum of the lesser of 0.1mg/kg or 4 mg.
Intuniv: Start with 1 mg once daily and adjust in increments of no more than 1mg/week. Maintan the dose within the range of 1 mg to 4 mg per day, depending on clinical response and tolerability.
2- agonists are contraindicated if there is a history in the patient or first degree relatives of sudden death, repeated fainting episodes, or arrhythmia. AACAP does not recommend a baseline EKG in otherwise healthy individuals. They must be tapered slowly when discontinuing due to the risk of rebound hypertension. 
Guanfacine 10-18 hours; Intuniv 24 hours 
 *indicates generic available
Common side effects of stimulants: decreased appetite, symptom rebound, sleep disturbance, nausea headache (transient), stomachache, tearfulness
Possible strategies to address side effects:
Decreased appetite: dose after meals, frequent snacks, drug holidays, liquid supplements (e.g. Boost, Ensure)
Symptom rebound: try sustained release stimulant, add small dose of short-acting in late afternoon
Sleep disturbance: bedtime routine, reduce afternoon dose, move dosing regimen to earlier time, eliminate caffeine, use medication as a last resort.
Irritability or tearfulness (less common): decrease dose, try another medication, consider comorbid conditions
Exacerbation of tics (rare): observe, reduce dose, try another medication
Psychosis/euphoria/mania/severe depression (rare): stop stimulant, refer to mental health specialist
 
N.B The FDA issued a black box warning regarding the risk of sudden death on stimulants. The rate of sudden death in children on stimulants does not exceed the rate in the general population. There is no evidence to suggest the need for pre-treatment cardiac evaluation (such as EKG) in otherwise healthy individuals. Cardiac evaluation should be undertaken for children with a history of cardiac disease and those with symptoms suggestive of significant cardiac disease or if there is a family history of cardiac disease including but not limited to sudden cardiac death before the age of 50 years old, cardiomyopathy, arrhythmias or tachycardia. This would include a history of severe palpitations, fainting, exercise intolerance not accounted for by obesity, or strong family history of sudden death. Postoperative tetralogy of Fallot, coronary artery abnormalities, and subaortic stenosis are known cardiac problems that require special considerations in using stimulants. Chest pain, arrhythmias, hypertension, or syncope may be signs of hypertrophic cardiomyopathy, which has been associated with sudden unexpected deaths in children and adolescents. Before a stimulant trial, such patients should be referred for consultations with a cardiologist for possible electrocardiography and/or echocardiography. If stimulants are initiated, then the patient should also be studied by the cardiologist during the course of treatment.  
                                                                                                                                                                                                    

 

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