Treating Adhd – the Basics Ohsujanuary 6, 2019
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TREATING ADHD – THE BASICS OHSUJANUARY 6, 2019 - JAY S. KOTHARI, MD - KEITH CHENG, MD $$$ DISCLOSURES $$$ OHSUNO FINANCIAL OR COMMERCIAL INTERESTS LEARNING OBJECTIVES • DIAGNOSIS AND DIFFERENTIAL DIAGNOSES OF ADHD • GENERAL PRINCIPLES OF ADHD PSYCHOPHARMACOLOGY • BE ABLE TO PRESCRIBE STIMULANTS • LEARN ABOUT NON-STIMULANT AND BEHAVIORAL OHSUAPPROACHES TO TREATMENT •Diagnosis, diagnosis, diagnosis – thorough psychiatric evaluation •Use of rating scales, Labs, EKG •Difference in pharmacokinetics “CHILDREN • Liver Tissue • GFR ARE NOT • TBW • Fat tissue content LITTLE • GI maturity ADULTS” •Difference in pharmacodynamics – different efficacy and tolerability / side effect profile •Safety/efficacy – being aware of black box warnings in OHSUchildren DSM-5 CRITERIA .Symptoms must be present for at least 6 months and impair social/academic/occupational function and be inconsistent with chronologic age .Some symptoms were present before 12 yrs .Present in 2 or more settings .Symptoms not due to other mental disorders OHSU.Inattention - must have 6 of 9 criteria .Hyperactivity - must have 6 of 9 criteria INATTENTIVE ADHD Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities (e.g., overlooks or misses details, work is inaccurate). Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations, or reading lengthy writings) Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction). Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked; fails to finish schoolwork, household chores, or tasks in the workplace). Often has difficulty organizing tasks and activities (e.g., difficulty managing sequential tasks; difficulty keeping materials and belongings in order; messy, disorganized, work; poor time management; tends to fail to meet deadlines) Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework; for older adolescents and adults, preparing reports, completing forms, or reviewing lengthy papers). Often loses things needed for tasks and activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, or mobile telephones) OHSUIs often easily distracted by extraneous stimuli (for older adolescents and adults, may include unrelated thoughts). Is often forgetful in daily activities (e.g., chores, running errands; for older adolescents and adults, returning calls, paying bills, keeping appointments) HYPERACTIVE/IMPULSIVE ADHD .Often fidgets with hands or feet or squirms in seat. .Often leaves seat in situations when remaining seated is expected (e.g., leaves his or her place in the classroom, office or other workplace, or in other situations that require remaining seated) .Often runs about or climbs in situations where it is inappropriate. (In adolescents or adults, may be limited to feeling restless). .Often unable to play or engage in leisure activities quietly. .Is often "on the go" or often acts as if "driven by a motor" (e.g., is unable or uncomfortable being still for an extended time, as in restaurants, meetings, etc; may be experienced by others as being restless and difficult to keep up with). .Often talks excessively. .Often blurts out answers before questions have been completed (e.g., completes people’s sentences and “jumps the gun” in conversations, cannot wait for next turn in conversation) OHSU.Often has trouble waiting his or her turn (e.g., while waiting in line). Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities; may start using other people’s things without asking or receiving permission; for adolescents and adults, may intrude into or take over what others are doing). WHAT WORKS BEST? •Well-established EBP’s: Behavioral Management Training (BMT) & Behavioral Contingency Management in the classroom •MTA study •MTA follow-up study OHSU•Interventions for Preschool kids at high-risk for ADHD: Meta-analysis CHILDHOOD ADULTHOOD Inattention Difficulty sustaining attention Difficulty sustaining attention Appears not to listen Makes careless errors Cannot organize, focus Easily distracted/forgetful Loses important items Hard to finish tasks Poor concentration Disorganized, misplaces things Hyperactivity Squirmy, Fidgety Inefficiencies in work Cannot stay seated Can’t sit through meetings Cannot wait for turn Internal restlessness “Drive by a motor” Over multitasks Talks excessively Impulsivity Blurts out answers Impulsive Job changes Cannot wait in line Drives too fast Constantly intrudes and interrupts others Interrupts others OHSUEasily frustrated CHILDHOOD VS ADULTHOOD IMPACT OHSUON LIFE DIFFERENTIAL DIAGNOSIS . Psychiatric conditions: . Children: low self-esteem, anxiety, depression, conduct disorder, oppositional defiant disorder, obsessive-compulsive disorder, poor social skills . Adolescents/adults: alcohol/drug abuse, anxiety, depression, personality disorder, bipolar disorder . General medical conditions - Hypothyroidism, severe anemia, lead poisoning, chronic illness, hearing or vision impairment, seizures, TBIs, FAS, Vit D deficiency, med s/e . Neurological conditions - Sleep disorders, Tourette’s syndrome, epilepsy (petit mal), OHSUspecific and general learning difficulties . Environmental factors - Unsafe or disruptive learning environment, school curriculum not matched to child’s ability, family dysfunction or poor parenting, child abuse/neglect, parental psychopathology, poor sleep (internet surfing for e.g.), bullying NEUROANATOMY OF ADHD OHSU http://www.bioscience.org/2000/v5/d/himelste/fulltext.htm •Stimulants (2 classes): • Immediate-release: Ritalin, Adderall, Focalin • Long-acting: Concerta, Adderall XR, Vyvanse, Focalin XR • Pro-drugs: Vyvanse •NRIs: Atomoxetine •Noradrenergic Modulators (alpha-2 agonists): • Short-acting: Tenex, Catapres • Long-acting: Intuniv, Kapvay •“Experimental” or off-label: • NDRI: Wellbutrin • SNRIs: Venlafaxine, Duloxetine • Modafinil (DRI) • Antipsychotics: Risperidone, 1st generation antipsychotics OHSU• Amantadine • TCAs STIMULANTS .“Stimulate” the brain to focus .70-85% response rate, effect size ~0.95 .Mechanisms of action .D vs L isomers .Effects/ side effects .Weight-based dosing or not? .Duration of action (AM, HW, wkn) OHSU.Drug holidays? Do: ◦ Increase dosing slowly to maximum of therapeutic range if no side effects ◦ Assess duration of action (what to do if medication is wearing off too early? I.e. increase or bunch up?) DOS AND ◦ Use input from school DONTS OF ◦ Try a different stimulant if 1st or 2nd trial fails DOSING Don’t: ◦ Begin too high (start low, go slow, especially if OHSUdev. delay) OHSU MPH FORMULATIONS By formulation: Liquid form Solutabs Cleaved: D-form (Focalin) Patch: 9 hours on, 15 hours off Delayed phase (Delexis system – just approved, will hit market 2019) By duration: Short acting: 3-4 hours Intermediate-acting: ER, LA**, CD Long-acting: Concerta (OROS) OHSU. FDA-approved max daily dose for MPH is 60mg, Concerta 72mg . ** Can sprinkle on food OHSU COMPARISON OF DOSE-CURVES DOSING MPH .According to AACAP, start at lowest dose (10mg BID), titrate up once a week (outpatient) .Other method: Weight based - Start ~0.5mg/kg/day up to 2mg/kg/day, titrate up every couple of days if needed (inpatient) .Focalin has to be dosed based on AMP dosing since it is a D-isomer (twice as potent) .Concerta dosing is higher than Ritalin (for e.g. 5mg BID/TID = 18mg Concerta, 15mg BID/TID = 54mg) – look for clinical relevance .Daytrana Patch – ~1.5x more potent than oral dose, 9 hours on, 15 hours off (on hip) OHSU.Reassess every year for continued need/dose AMP FORMULATIONS By formulation: By duration: • Amphetamine – ER, ODT, liquid • Short-acting: 3-4 hours • Methamphetamine (not used, • Intermediate-acting: 6-8 hours “Desoxyn” – FDA approved for • Long-acting: Vyvanse obesity) • Dextro-amphetamine - IR, ER, liquid OHSU• Mixed salts (D, L) – IR, ER • Pro-drug (Vyvanse) DOSING AMP .According to AACAP, start at lowest dose (5mg BID), titrate up once a week (outpatient) .Other method: Weight based - Start ~0.25mg/kg/day up to 1mg/kg/day, titrate up every couple of days (inpatient) .Remember, mixed salts are usually 3:1 D vs L isomers, although Evekeo which is 1:1 – manufacturers say this leads to less s/e .Vyvanse is a pro-drug that converts to all D-AMP: needs 2 hours to activate. Less toxicity, abuse, diversion OHSU.Reassess every year for continued need/dose WHAT TO DO IF… .15 y/o weighing 50kg comes in with dx of ADHD? Med/dosing . Has comorbid ODD and impulsivity . Has comorbid tic disorder . Tics get worse after use of stimulant . Has comorbid SUD . Has appetite loss after starting stimulant . Has disruptive sleep to start out with . Has a family hx of CV disease OHSU. Has poor insurance Do stimulants cause addiction? According to a study in the Br J Psychiatry July 11, 2013, stimulant medications appear to lower the risk for substance abuse disorders in adolescents with ADHD In a large, prospective, longitudinal study investigators from the SUNY found that adolescents with ADHD who were not treated with a stimulant medication for their disorder had a 2-fold increased risk of developing an SUD compared with their counterparts who were treated. Untreated