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 adolescents with ADHD also had a 2.6-fold increased risk of developing an SUD compared with a healthy, age-matched OHSUcontrol group. Multiple past studies show no connection. Do stimulants cause significant growth retardation?
2008 study showed that treatment with stimulant medication led to statistically significant delays in height and weight. Harvard ADHD team found statistically significant evidence of attenuation of these deficits over time. The qualitative review suggested that growth deficits may be dose dependent, deficits may not differ between methylphenidate and amphetamine Treatment cessation may lead to normalization of growth, and further research should assess the idea that attention- deficit/hyperactivity disorder itself may be associated with OHSUdysregulated growth. Are tics caused by stimulants?
To date, research has not established a “definitive and causal” relationship of the emergence of tics with stimulant use. Though some studies have indicated that transient tics may occur more often in a population of ADHD patients (with and without a history of tic disorders) treated with stimulants, this data remains controversial…Pidsosny & Virani---2006 Researchers studied 136 children aged 7 to 14 years with ADHD and a chronic tic disorder taking MPH. Throughout the 4-month study, researchers found improvement in all of the children who received medication. "Not only did tics not worsen during treatment, the severity of tics actually decreased in all treatment groups," writes study author Roger OHSUKurlan, MD, of the University of Rochester Medical Center in New York Are EKGs necessary for all youth on stimulants? .April 2008 AHA released policy statement that all youth on stimulants should receive EKG .May 16, 2008, the AHA and AAP, and AACAP, jointly issued a news release clarifying that obtaining an ECG before starting medication was “reasonable” but not mandatory. .The risk of cardiac arrest from stimulants is no greater than Sudden Cardiac Arrest in the general pediatric population—Gould et al., OHSU2009 ATOMOXETINE
Selective NRI – inhibits the presynaptic NET 65% response rate in RCT Dosing 0.5-1.2 mg/kg/day. Max 1.4 mg/kg/day but not above 100mg Hepatotoxicity Black box warning Can use QD or BID OHSU6-8 weeks for full effect ALPHA-2 AGONISTS
Good in kids that don’t tolerate stimulants; or with comorbidities; or adjunct use with stimulants When d/c’ing, taper slowly due to rebound effects Intuniv Dose range 1-4mg TDD FDA max 7mg, but usually above 4mg not helpful Pharmacokinetics are different in IR vs ER, so not mg-to-mg convertible 0.05-0.08 mg/kg/day (max 0.12 mg/kg/day) Titrate starting at 1mg/day Kapvay Dose range 0.1-0.4mg/day OHSU FDA max 0.4mg/day Start 0.1mg QHS to start Above 0.2mg better to split dose Pharmacokinetics differ greatly in IR vs ER OUTSIDE-THE-BOX TREATMENTS
Modafinil, Amantadine Upcoming: Metadoxine(?) Neurofeedback? What if parents want “natural” remedies? Psychoeducation ADHD diet (INCA study), no artificial colors Structure/schedule, exercise, good sleep hygiene, sensory issues (OT eval) RLS in ADHD kids: Ferrous sulfate, magnesium ADHD Supplements: phosphatidylserine, Omega-3 Sleep supplements: melatonin, magnesium OHSU Impulsivity/hyperactivity: Zinc, B6 Cognitive: Vit. D levels (correct low levels) NUTRITIONAL ASPECTS
• Sugar? • Dyes • Iron • Omega-3 Fatty Acids OHSU• Zinc/Magnesium/Pyridoxine Make sure parents know what ADHD is and what the Parent/Family treatments are available Psychoeducation Encourage the parents to include siblings in the discussion when appropriate Address skepticism with available science Talk about what is helpful and not helpful in interacting with OHSUtheir child with ADHD Optimizing Environmental Factors Eating/nutritional/diet Habits Sleeping Habits Video Game: use late at night/hours per day/other addictions Substance Abuse, caffeine use Trauma/being bullied at school or in the community OHSUFamily Stresses/Dynamics Optimizing Nutritional Status ØBalanced Nutritious Diet ØRaw foods vs processed foods ØHigh Omega 3 fatty acids ØIron rich foods OHSUØMinimize/Eliminate Junk Food Iron Deficiency Hypothesis ØIron is critical in the synthesis of dopamine ØIron is essential for the myelination of brain cells ØSome studies show that iron stores are low in up to 84% of ADHD youth OHSUØFerritin levels <30 ng/ml need treatment Fish Oil for ADHD ØSeveral studies have shown that ADHD youth have lower levels of omega 3 fatty acids ØSeveral studies have shown that ADHD symptoms are improved with fish oil, flaxseed oil, and primrose oil ØKnow difference between ALA and DHA/EPA OHSUØMore studies, continuing to learn more Vitamins and Minerals
Significantly lower levels of magnesium, zinc, and B-complex (focus on B6) vitamins have been measured in hair of youth with autism and ADHD However treatments with vitamins & minerals OHSUstill need to be completed Common Principles of Behavior Management Training
Minimize Understanding eliminate negative Child Embracing Praise Planned Ignoring parental Development responses
Positive Enhancing Special Time, Reinforcement, Using Time-outs problem/conflict ”Parental Intermittent appropriately solving skills Attention” Reinforcement
OHSUParental Support Examples of Behavior Management Training ØParent Child Interaction Therapy (PCIT) ØKazdin Behavior Management Training ØParent Management Training – Oregon Model (PMTO) ØCollaborative Problem Solving ØRussell Barkley ØRex Forehand OHSUØLove & Logic 01 02 03 04 05 Encouragement: Limit Setting: Monitoring & Family Problem Positive Parent Teaching children Responding to Supervision: Solving: An Involvement: new behavior problem behavior Checking on organized method of Parents through the use of with negative, children’s behavior making decisions demonstrating praise and nonphysical at home and away with family input. interest, caring and OHSUincentives. consequences. from home. attention. Parent Management Training -Oregon The Kazdin Method Understanding parenting myths Understanding basic behavior theory Understanding context in using behavior plan Developmental considerations OHSUUnderstanding the limitations of punishment Parent-Child Interaction Therapy (PCIT) This treatment focuses on two basic interactions: §Child Directed Interaction (CDI) is similar to play therapy in that parents engage their child in a play situation with the goal of strengthening the parent-child relationship §Parent Directed Interaction (PDI) resembles clinical behavior therapy in that parents learn to use specific behavior management OHSUtechniques as they play with their child. Russell Barkley
Positive Attention and Praise Using rewards and incentives effectively Staying calm and consistent Using Time-outs OHSUTargeting behavioral issues Rex Forehand Understanding child temperament Know factors contributing to disruptive behavior Strengthening parent child relationship Collaborative discipline OHSUParental stress Optimize School Collaboration Establish IEP or 504 accommodation plan if needed Routine communication with teacher Extracurricular help like homework club OHSUTechnology support like keyboards, online assignments THANK YOU!
EBP RESOURCES: Online – the Cochrane Collaboration Journal - Silverman WK, Hinshaw SP. The Second Special Issue on Evidence-Based Psychosocial Treatments for Children and Adolescents: A Ten-Year Update. J Clin Child Adolesc Psychol. 2008 Jan-Mar;37(1) Book – Evidence-Based Psychotherapies for Children and Adolescents, 2nd Ed by John Weisz and Alan Kazdin, Guilford Press OHSU2010 Other Bibliography available upon request