1 Discriminate between various subtypes of ADHD based on symptom presentation Attention Deficit Hyperactivity Disorder ADHD Symptoms must be present in multiple settings at least 2 for 6 months Symptoms are outside the realm of what is considered age appropriate Symptoms must cause functional impairment in school and or home before a diagnosis is made Onset of symptoms must be before 12 years of age typically by age 3 Other potential causes medical psychiatric disorder learning disability ruled out Inattention factor 6 or 5 in adults of the following Careless mistakes or inattention to detail attention span Poor listener Cannot follow instructions and does not complete tasks Difficulty organizing tasks and activities Avoids and or dislikes chores or homework Loses things needed for tasks and activities Easily distracted by extraneous stimuli Forgetful in daily activities Hyperactivity Impulsivity factor 6 or 5 Hyperactivity Fidgets with hands feet or squirms in chair Cannot remain seated in the classroom Uncontrollable inappropriate restlessness Difficulty in engaging in play or leisure activities quietly Often on the go and appearing driven by a motor Excessive talking Impulsivity Blurts out answer prior to completion of question Difficulty waiting turn Interrupts or intrudes on others Subtypes ADHD Predominantly Inattentive Type ADHD Predominantly Hyperactive Impulsive Type ADHD Combined Type For older adolescents and adults 17 years of age at least 5 symptoms are required 2 Recommend the most appropriate pharmacotherapy to treat ADHD based on medication and patient characteristics MPH methylphenidate and dexmethylphenidate AMP amphetamine includes mixed amphetamine salts dextroamphetamine lisdexamfetamine TCA tricyclic antidepressant GXR guanfacine extended release CLON XR clonidine extended release Alpha2 agonist clonidine and guanfacine immediate release Pharmacotherapy o Uncomplicated ADHD First line treatment stimulants Methylphenidate dexmethylphenidate Dextroamphetamine mixed amphetamine salts Trial of one course of each type will often take place first before moving on to the next level of treatment due to inadequate response Second line treatment atomoxetine or bupropion Third line treatment tricyclic antidepressant or 2 adrenergic agonist Treat comorbidity first prior to trial of stimulant o ADHD with other comorbidities Bipolar disorder severe aggression mood stabilizer or SGA Anxiety depression antidepressant Tourette s disorder dopamine antagonist Stimulants OK for tourettes Expected ADHD symptom improvement Core symptoms o Inattention o Impulsivity o Hyperactivity Other symptoms possibly o Impulsive aggression o Social interactions o Academic efficiency o Academic accuracy o Family dynamics o Possible DA uptake blockade blocking DA transport or carrier proteins NE may be involved o Metabolism occurs in the liver via de esterification to a minimally active metabolite ritalinic o Time to peak concentrations for MPH may be delayed with a high fat breakfast no other o Immediate release IR to see if responds to a lesser extent acid changes in pharmacokinetics are seen with or without food Methylphenidate MPH Mechanism of action Mild CNS stimulant with minimal effects in the periphery Reach peak plasma concentration in 1 3 hrs clinical effects seen within 30 60 mins Duration of action ranges from 3 6 hrs Often given twice daily i e morning and noon don t give late in the day to risk of nighttime insomnia o MPH sustained release SR and MPH extended release ER Release MPH slowly over 6 8 hrs with peak concentrations in 4 5 hrs Products usually given twice daily Careful too slowly then insomnia o MPH long acting LA 50 of MPH dose released immediately onset within 30 60 mins peak concentrations within 1 3 hrs A second peak occurs 5 6 hrs after ingestion Product given once daily o MPH controlled delivery CD 30 of MPH dose released immediately and 70 released continuously second peak 5 6 hrs after ingestion symptoms worse in the morning or later in the day Some patients may still require supplemental MPH IR in the afternoon with either MPH LA or MPH CD o MPH OROS concerta When symptoms occur inform choice between MPH LA and MPH CD e g are the with either MPH LA or MPH CD First peak occurs within 2 hrs then there is a gradual and a 2nd peak within the next 3 4 hrs followed by a slow release phase with a gradual decline Total duration of action for this product is approximately 10 12 hrs o MPH transdermal Slower onset of action than oral MPH products clinical efficacy not seen for at least 2 hrs after placement average 3 hrs Peak concentrations seen 8 hrs after placement o Dex MPH IR Patch should be removed after 9 hrs clinical effects of MPH may be seen for up to 3 hrs after removal the patch may be removed earlier if clinically warranted Slightly faster time to peak of 1 1 5 hrs compared with MPH Clinical effects seen within 30 60 mins Duration of action approximately 6 hrs Delivers 50 of the dose immediately with peak at 1 5 hrs and a 2nd peak at 6 5 hrs o Dex MPH XR Amphetamine Mechanism of action sympathomimetic agents that stimulate the release of NE and DA in the CNS o Enhance the release of NE in the periphery from adrenergic nerve terminals o At doses may stimulate the release of serotonin 5 HT as well as act as an agonist at 5 HT receptors Pharmacokinetics o Elimination half life for amphetamine varies by age Children 6 12 yrs old d amphetamine 9 hrs l amphetamine 11 hrs Adolescents 13 17 yrs old d amphetamine 11 hrs l amphetamine 13 14 hrs Adults d amphetamine 10 hrs l amphetamine 13 hrs o Amphetamine salts are metabolized hepatically via cytochrome P450 monooxygenation and o A high fat meal may delay the time to peak concentrations of amphetamine products by as o Dextroamphetamine IR Phase II glucuronidation much as 2 hrs Reach peak concentration in 2 hrs while XR products reach peak in 8 hrs Onset of clinical effects seen within 30 60 minutes Usually given at least twice daily similar to MPH IR Reach peak concentration in 3 hrs o Mixed amphetamine salts IR o Mixed amphetamine salts XR ADHD 50 of dose released immediately with the first peak within 3 hrs and the second peak within 7 hrs Once daily formulation simulating twice daily dosing using beaded technology Prodrug converted to dextroamphetamine and L lysine in the gut Delay effect Peak concentrations seen within 3 4 hrs some say b c prodrug it is less abuseable Not really 3 List relevant therapeutic outcomes