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Practice Pearls for Managing ADHD in Children and Adolescents
Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRNClinical Professor of Psychiatry and NursingInstitute for Juvenile Research, Department of Psychiatry University of Illinois at Chicago
Disclosure• The faculty have been informed of their responsibility to disclose to the
audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration).– Dr. Carbray will be discussing off-label use of medications in this presentation
and will identify those medications.
• Applicable CME staff have no relationships to disclose relating to the subject matter of this activity.
• This activity has been independently reviewed for balance.
• Brand names are included in this presentation for participant clarification purposes only. No product promotion should be inferred.
Epidemiology of ADHD, Trends, and Environmental Influences
What is ADHD?• Most common psychiatric disorder seen in childhood• Over 8 million Americans affected across the lifespan
• 6.4 million US school-aged children affected• 2 million preschoolers
• 7% to 10% elementary school children, 3% to 4% adults• Underdiagnosed in lower socioeconomic status, diverse cultures
• Males more than Females (4:1 ratio)• 20% to 35% of children with ADHD have parents with the disorder
Development: PrematurityEnvironmental risks: Maternal drug use/smoking, inconsistent parenting practices, lead exposure
The prevalence has grown over the past years by 50%SAMHSA. www.samhsa.gov/treatment/mental-disorders/adhd. Accessed February 7, 2018. CDC. www.cdc.gov/ncbddd/adhd/data.html. Accessed February 7, 2018. Weed ED. Int J Psychiatry Med. 2016;51(2):120-136. Subcommittee on Attention-Deficit/Hyperactivity Disorder, et al. Pediatrics. 2011;128(5):1007-1022.
Impact of Untreated ADHD in Children and Adolescents
• Risk behaviors are common, more so with untreated illness
• 30% repeat a grade• 30% fail to complete high school• 38% cause or have an unwanted pregnancy (compared to 4% of teens)• 17% have contracted a sexually transmitted disease• Only 5% to 10% complete college• Untreated, more likely to self-medicate
• National health care costs for children $21 to $44 billion
Kessler E. Untreated ADHD: Lifelong Risks. www.smartkidswithld.org/getting-help/adhd/untreated-adhd-lifelong-risks. Accessed February 7, 2018. SAMHSA. www.samhsa.gov/treatment/mental-disorders/adhd. Accessed February 7, 2018. Weed ED. Int J Psychiatry Med. 2016;51(2):120-136. Doshi JA, et al. J Am Acad Child Adolesc Psychiatry. 2012;51(10):990.e2-1002.e2.
Risks with Untreated Illness• Using Danish national registers,
followed a cohort of 710,120 individuals, including 4557 individuals diagnosed with ADHD before age 10 years
• Looked at before and after treatment, and compared with controls
• Children with ADHD had an increased risk of injuries compared with other children
• Treatment with ADHD medications reduced the risk of injuries by up to 43% and emergency ward visits by up to 45% in children with ADHD
• Taken together with previous findings of accidents being the most common cause of death in individuals with ADHD, these results are of major public health importance
Dalsgaard S, et al. Lancet Psychiatry. 2015;2(8):702-709. Johnson JA, et al. J Child Adolesc Psychopharmacol. 2017;27(8):747-754.
Pathophysiology• Highly inheritable 60% to 90%
across generations• Twin studies confirm a genetic link
• Dopamine and norepinephrine neurotransmitters and transporters– Attention, arousal, impulsivity,
mood– Glutamate– Newer role of GABA?
• Structural differences – Lessened activity in prefrontal
cortex, caudate, globus pallidus
GABA = gamma-aminobutyric acid.Larsson H, et al. Psychol Med. 2014;44(10):2223-2229. Sowell ER, et al. Lancet. 2003;362(9397):1699-1707. Battel L, et al. J Child AdolescPsychopharmacol. 2016;26(6):555-561. Volkow ND, et al. Am J Psychiatry. 1998;155(10):1325-1331. Findling RL. Clin Ther. 2008;30(5):942-957.
Cortical Maturation
Kaplan–Meier curves illustrating the proportion of cortical points that had attained peak thickness at each age for all cerebral cortical points (Left) and the prefrontal cortex (Right). The median age by which 50% of cortical points had attained their peak differedsignificantly between the groups (all P<1.0 × 10-20).Shaw P, et al. Proc Natl Acad Sci U S A. 2007;104(49):19649-19654.
Gray Matter Density
Regions where the ADHD group had delayed cortical maturation, as indicated by an older age of attaining peak cortical thickness.Shaw P, et al. Proc Natl Acad Sci U S A. 2007;104(49):19649-19654.
ADHD: Children < 17 years
• Group of conditions with onset in the developmental period– Manifest early in development– Often before child enters school– Characterized by developmental
deficits impacting social, personal, academic, or occupational functioning
• Criteria A: A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with development or function– Inattention: At least 6/9
symptoms– Hyperactivity-impulsivity: At least
6/9 symptoms• Criteria B: Several inattentive or
hyperactive-impulsivity symptoms were present prior to age 12 years
Neurodevelopmental Disorders Criteria
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
Symptoms
Often…• fails to give close attention to details or makes
careless mistakes in schoolwork, at work, or with other activities
• has trouble holding attention on tasks or play activities
• does not seem to listen when spoken to directly• does not follow through on instructions and fails to
finish schoolwork, chores, or duties in the workplace (eg, loses focus, side-tracked)
• has trouble organizing tasks and activities• avoids, dislikes, or is reluctant to do tasks that require
mental effort over a long period of time (such as schoolwork or homework)
• loses things necessary for tasks and activities (eg, school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones)
• easily distracted• forgetful in daily activities
Often… • fidgets with or taps hands or feet, or squirms in
seat• leaves seat in situations when remaining seated is
expected• runs about or climbs in situations where it is not
appropriate (adolescents or adults may be limited to feeling restless)
• unable to play or take part in leisure activities quietly
• “on the go” acting as if “driven by a motor”• talks excessively• blurts out an answer before a question has been
completed• has trouble waiting his/her turn• interrupts or intrudes on others (eg, butts into
conversations or games)
Inattention Hyperactivity/Impulsivity
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
Diagnostic Tools• Conners Comprehensive Behavior Rating Scales (CBRS)• Vanderbilt ADHD Diagnostic Rating Scale (VADRS) • Child Behavior Checklist (CBCL)• Child Attention Profile (CAP)• Barkley School Situations Questionnaire (SSQ)• ADD-H Comprehensive Teacher/Parent Rating Scales (ACTeRS)
• Diagnosis is not made by a diagnostic tool
National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management. www.nice.org.uk/guidance/cg72. Accessed February 7, 2018.
Comorbidity
Children and adolescents with ADHD, N=1478. Steinhausen HC, et al. Eur Child Adolesc Psychiatry. 2006;15 Suppl 1:I25-I29.
Disruptive Mood Dysregulation Disorder• Criteria A: Severe recurrent temper
outbursts manifested verbally and/or behaviorally that are disproportionate in intensity or duration to the situation
• Criteria B & C: Outbursts are inconsistent with developmental level and occur on average of ≥ 3 × per week. Persistent negative mood in between and observable by others
• Present 12 months < 3 months symptom free
• Criteria H: Age of onset before 10 years, at least 6-years-old
• Child/Adolescent Symptom Inventory (CASI)
• WHO Composite International Diagnostic Interview (CIDI)
• Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)
• Use Child Mania Rating Scale (CMRS) to differentiate
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013. Margulies DM, et al. Bipolar Disord. 2012;14(5):488-496. Leibenluft E. Am J Psychiatry. 2011;168(2):129-142. Fristad MA, et al. J Child Adolesc Psychopharmacol. 2016;26(2):138-146.
What does ADHD look like in children?
Therapy Interventions
Many Do Not Receive Good Evidence-Based Care• 50% of children aged 2 to 5 years receive psychotherapy as primary source
of therapy, 10% receive neither psychopharmacotherapy or psychotherapy• 17.5% of children with ADHD aged 4 to 17 years are not receiving
recommended first-line stimulants or behavior therapy• If behavioral therapy is not introduced with the start of medications, families
are less likely to introduce it later • Common titration issues can result in early termination of effective treatments
– Increase dose slowly– Failure to assess duration of action – Under dosing and overdosing effects/adverse effects
Visser SN, et al. J Am Acad Child Adolesc Psychiatry. 2014;53(1):34.e2-46.e2. CDC. MMWR Morb Mortal Wkly Rep. 2010;59(44):1439-1443. Visser SN, et al. Prev Chronic Dis. 2013;10:E09. CDC. www.cdc.gov/ncbddd/adhd/features/key-findings-adhd72013.html. Accessed February 7, 2018.
School-Based InterventionsAccommodations• Allow some restlessness in work area• Color coded binders/text• Use participatory teaching• Use technology for practice of skills• Assign a study buddy/use peer tutors• Balance active learning with more
didactic instruction• Touch a child lightly to get attention,
make it interesting• Most difficult subjects early in the day• Require continuous note-taking• Use after school supports
• Don’t retain students• Establish behavioral control of the
classroom• Decrease workload• Smaller quotas of work with more
breaks• Traditional desk arrangement• Seat student closer to teacher• Target productivity• Don’t send home unfinished work• Give out weekly assignments• Reduce homework in elementary
settingsBarkley RA. Managing ADHD in School: The Best Evidence-Based Methods for Teachers. Eau Claire, WI: PESI Publishing & Media; 2016.
Home/School Communication• Daily school-home report card• This tool allows parents and teacher to
communicate regularly, identifying, monitoring, and changing classroom problems. It is inexpensive and minimal teacher time is required
• Teachers determine the individualized target behaviors
• Teachers evaluate targets at school and send the report card home with the child
• Parents provide home-based rewards; more rewards for better performance and fewer for lesser performance
• Teachers continually monitor and make adjustments to targets and criteria as behavior improves or new problems develop
• Use the report card with other behavioral components such as commands, praise, rules, and academic programs
Barkley RA. Managing ADHD in School: The Best Evidence-Based Methods for Teachers. Eau Claire, WI: PESI Publishing & Media; 2016.
School Letter
Why treat the parents?
• Impulsiveness• Inconsistent discipline• Lower rates of positive
reinforcement• Lower child monitoring• Higher rates of expressed emotion
• Parent ADHD needs to be addressed as well
• Encouragement of positive behavior• Systematic, mild consequences for
negative behavior• Monitoring• Problem-solving• Positive involvement• Providing clear directions• Observing and recording behavior
change• Identifying and regulating emotions• Fostering active communication• Promoting school success
Parents of Children with ADHD Parent Management Training
Starck M, et al. Neuropsychiatr Dis Treat. 2016;12:581-588. Takeda T, et al. J Pediatr. 2010;157(6):995.e1-1000.e1. California Evidence-Based Clearinghouse for Child Welfare. Parent Management Training - Oregon Model (PMTO®). www.cebc4cw.org/program/the-oregon-model-parent-management-training-pmto/detailed. Accessed February 7, 2018.
Evidenced-Based Practice: MTA Trial• Superiority of multimodal treatment
regimens for ADHD compared with the commonly available community care
• Symptom and functioning improvements brought about by multimodal therapy lapsed after cessation of therapy
• ADHD is a chronic condition, requiring continuous, long-term, and well-monitored treatments
• ADHD symptoms persist into adulthood in about half the sample
The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry. 1999;56(12):1073-1086. Jensen PS, et al. J Dev Behav Pediatr. 2001;22(1):60-73.
Psychotherapy and Psychopharmacotherapy• Youngest children (4–5 years): Behavior therapy first• School-aged children: Behavior therapy plus medication• If you do not introduce therapy along with medication, families may be less
likely to engage in it later• In primary care, symptom improvement is maximized with frequent contact
with parents, school input, and check-ins • For maintained long-term effects, ongoing treatment
National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management. www.nice.org.uk/guidance/cg72. Accessed February 7, 2018. Epstein JN, et al. J Am Acad Child Adolesc Psychiatry. 2017;56(6):483.e1-490.e1.
Psychopharmacology
ADHD Treatment
Methylphenidate-based
Amphetamine-based
Nonstimulants
Stimulants’ Proposed Mechanism of Action
ADHD Clinic. www.adhd1clinic.com/3.html. Accessed February 7, 2018. Stahl SM. J Clin Psychiatry. 2010;71(1):12-13.
Why do we stimulate hyperactive children?
Methylphenidate-Based Medications
• Ritalin® (MPH)• Ritalin SR® (sustained-release MPH)• Concerta® (extended-release OROS®
MPH)• Metadate CD® (extended-release MPH)• Focalin® (dexMPH)• Ritalin LA® (extended-release SODAS™
MPH)• Focalin XR® (extended-release
SODAS™ MPH)
• Daytrana® (MPH transdermal patch)• Quillivant XR® (oral suspension made up
of coated particles containing polymer-matrix–bound MPH)
• Aptensio XR® (MPH oral capsule containing multilayered beads)
• Quillichew ER™ (MPH chewable tablet)• Cotempla XR-ODT™ (MPH extended-
release)
Older Newer
MPH = methylphenidate; OROS = osmotic-controlled release oral delivery system; SODAS = spheroidal oral drug absorption system; ODT = orally disintegrating tablet.Jain R, et al. Prim Care Companion CNS Disord. 2016;18(4). US Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. www.accessdata.fda.gov/scripts/cder/daf/.
Amphetamine/Dextroamphetamine-Based• Adderall® (mixed amphetamine salts)
– Approved for age ≥ 3 years – Recommended for children < 6 years
• Adderall XR® (extended-release mixed amphetamine salts)• Vyvanse® (lisdexamfetamine)
Jain R, et al. Prim Care Companion CNS Disord. 2016;18(4). US Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. www.accessdata.fda.gov/scripts/cder/daf/.
Contraindications and Monitoring• Heart disease, heart rhythm disorder• Coronary artery disease (hardened
arteries)• History of heart attack• High blood pressure• A history of mental illness or psychosis• Peripheral vascular disease such as
Raynaud’s syndrome• Epilepsy or other seizure disorder• History of drug or alcohol addiction• Tics• Glaucoma• Use with caution with comorbid anxiety
• Pharmacokinetics: IR 2 to 3 hours, XR 10 to 12 hours
• Weight-based dosing• Gender differences: Females 20% to
40% higher systemic exposure but this appears to be weight-based (require less dose and more prone to side effects)
• Rapid metabolizers
Weed ED. Int J Psychiatry Med. 2016;51(2):120-136. Markowitz JS, et al. J Child Adolesc Psychopharmacol. 2017;27(8):678-689. Weiss MD, et al. Atten Defic Hyperact Disord. 2017 Nov 4;[Epub ahead of print]. Riera M, et al. Psychopharmacology. 2017;234(17):2657-2671.
ADHD Medications: Guidelines• Advantages/challenges to long-acting forms• Medication effect is 8 to 12 hours• Don’t be afraid to push the dose• Side effects: Dizziness, insomnia, irritability, headache, dysphoria-crying,
decreased appetite, tics• Adverse effects: Toxic psychosis (in high doses), hair loss • Cardiac concerns• Drug/drug interactions: Rare• Withdrawal issues• Overdose, diversion, and treatment—safety issue
Nonstimulants• Less studied, different action• Also used off-label for aggression• Side-effect profiles
– Atomoxetine: Headache, sleepiness
– Clonidine/Guanfacine: Flushing, dizziness, low blood pressure
• Atomoxetine: Comorbid anxiety
α2-Adrenergic Agonists • Clonidine• Guanfacine
Kratochvil CJ, et al. J Am Acad Child Adolesc Psychiatry. 2006;45(8):919-927. Newcorn JH, et al. J Child Psychol Psychiatry. 2016;57(6):717-728. Jain R, et al. J Am Acad Child Adolesc Psychiatry. 2011;50(2):171-179.
Newer Medications• Dyanavel XR® (amphetamine)
– Oral suspension 2.5 mg/mL– > 6 years– Up to 13 hours
• Mydayis® (mixed amphetamine salts)– 12.5, 25, 37.5, 50 mg ER
capsules– ≥ 13 years– Up to 16 hours
• Zenzedi® (dextroamphetamine)– 2.5, 7.5, 15, 20, and 30 mg
tablets– 3 to 16 years– 4 to 6 hours
• Evekeo® (amphetamine)– 5, 10 mg tablets– > 3 years– 10 hours
• Adzenys XR-ODT™ (extended-release amphetamine)– 3.1 mg, 6.3 mg, 9.4 mg, 12.5 mg,
15.7 mg, 18.8 mg – 6 to 17 years– 10 hours
US Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. www.accessdata.fda.gov/scripts/cder/daf/.Zenzedi® [prescribing information]. Dextroamphetamine sulfate. http://zenzedi.com/docs/PIandMedicationGuide.pdf. Atlanta, GA: Arbor Pharmaceuticals. Accessed February 7, 2018. Evekeo® [prescribing information]. Amphetamine sulfate tablets. www.evekeo.com/pdfs/evekeo-pi.pdf?v=1513964354081. Atlanta, GA: ArborPharmaceuticals. Accessed February 7, 2018.
Phase 2 and 3 Clinical Trials Ongoing• Dasotraline
– Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)
• SPN-810 (molindone hydrochloride): Impulsive aggression with ADHD
• SPN-812
• New delivery systems/formulas
• Mindfulness
• Neurofeedback
• Cogmed
• TMS
TMS = transcranial magnetic stimulation.ClinicalTrials.gov.
Vayarin®
• Form of omega-3 fatty acids (phosphatidylserine, EPA, and DHA)
• Nonstimulant• Take 2 caps daily• No age indication
• Medical food, not FDA approved• Modest efficacy has been shown;
most often used as an adjunct
EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid.Manor I, et al. Eur Psychiatry. 2012;27(5):335-342. Puri BK, et al. Prostaglandins Leukot Essent Fatty Acids. 2014;90(5):179-189.Iannelli V. Vayarin for ADHD. www.verywellmind.com/vayarin-for-adhd-2633136. Accessed February 8, 2018.
Comorbidities Combination Treatments• Anxiety• Conduct • Depression• Bipolar disorder• Psychotic disorders
• Attenuation of cardiac adverse stimulant effects with guanfacine combination therapy
Snircova E, et al. Pediatr Int. 2016;58(6):476-481. Ng QX. J Child Adolesc Psychopharmacol. 2017;27(2):112-116. Sayer GR, et al. J Child Adolesc Psychopharmacol. 2016;26(10):882-888.
Prevalence and Treatment Outcomes of Persistent Negative Mood among Children with ADHD and Aggressive Behavior
• N=156 children with ADHD and aggressive behavior
• Baseline and after treatment with stimulant and family based treatment (37.83 mean days of treatment)
• Change in mood symptoms and aggressive behaviors
• Aggression decreased with stimulant monotherapy and behavioral treatment even in children with moodiness. Mood improved as well
• Children with DMDD and ADHD may have a positive mood response to stimulants
DMDD = disruptive mood dysregulation disorder.Blader JC, et al. J Child Adolesc Psychopharmacol. 2016;26(2):164-173.
NeurofeedbackNeurofeedback aims to change behavior by changing the brain.
The brain produces measurable electrical signals. Neurofeedback measures these electrical waves, usually with a device called an EEG.
Like other electrical devices, brain waves cycle at specific frequencies. The 5 different brain waves are alpha, beta, gamma, delta, and theta. They each have different frequencies, and these are measurable by an EEG.
Some research suggests that people with ADHD have too many theta waves, and too few beta waves. Neurofeedback claims to correct this difference by training people with ADHD to use their brains differently.
Neurofeedback practitioners begin by attaching electrodes to the head in order to measure brain activity. This produces an ongoing screen printout of brain waves that can be watched during the session.
Based on brain wave feedback, the neurofeedback provider will instruct the person to perform a specific task.
The process may involve sounds and other stimuli to encourage the brain to process information differently. There might be music or a tone, or sounds that suddenly stop or start.
This approach can interrupt, alter, or amplify brain activity based on feedback from the EEG.
Supporters of neurofeedback claim that this steady feedback can slowly alter brain waves. As brain waves change, so too do the symptoms of psychological conditions, and it may help to improve general performance.
Does neurofeedback work?Studies on neurofeedback's effectiveness in treating people with ADHD are very mixed.
In 2014, parental assessments given in a further meta-analysis indicated that neurofeedback brought improvements in impulsiveness, inattention, and hyperactivity. In the same study, teachers felt that improvements occurred only in inattention.
EEG = electroencephalograph. Villines Z. Is Neurofeedback an Effective Treatment for ADHD? www.medicalnewstoday.com/articles/315261.php. Accessed February 13, 2018. Micoulaud-Franchi JA, et al. Front Hum Neurosci. 2014;8:906. Janssen TW, et al. J Child Adolesc Psychopharmacol. 2016;26(4):344-353.
Neurofeedback• RCT of 112 children with ADHD• Compared stimulant treatment with
neurofeedback 30 sessions• Matched group-MPH and placebo
group• Only stimulant group demonstrated
improvements in brain function related to response inhibition
RCT = randomized controlled trial.Janssen TW, et al. J Child Adolesc Psychopharmacol. 2016;26(4):344-353.
Clinical Pearls
Wide variation in costNo holidays
Don’t be afraid to titrate doseUse formulary options first
Combined therapies
Pearls• Diversion• EKGs• Heart rate/blood pressure• Growth• Appetite suppression• Headaches• Prior authorizations• Parent acceptance of medications• Ethnically diverse youth
EKG = electrocardiogram.Pham T, et al. J Child Adolesc Psychopharmacol. 2017;27(8):741-746. Poulton AS, et al. Int Clin Psychopharmacol. 2016;31(2):93-99. Vitiello B, et al. Am J Psychiatry. 2012;169(2):167-177. Paidipati CP, et al. J Am Psychiatr Nurses Assoc. 2017;23(2):90-112. Cummings JR, et al. Pediatrics. 2017;139(6).
Avoid Treatments We Know Do Not Work • Megavitamins, minerals, antioxidants• Omega-3s• Sensory integration training• Chiropractic skull manipulation• Play therapy/Psychotherapy
– Not behavior therapy, the bulk of which is practice not training
Barkley RA. Managing ADHD in School: The Best Evidence-Based Methods for Teachers. Eau Claire, WI: PESI Publishing & Media; 2016.
Will taking medication for ADHD lead to my child thinking drugs are OK?
Untreated ADHD will
Wilson JJ, et al. Curr Psychiatry Rep. 2001;3(6):497-506. Kollins SH. J Atten Disord. 2008;12(2):115-125. Harstad E, et al. Pediatrics. 2014;134(1):e293-e301. Wilens TE, et al. Curr Psychiatry Rep. 2007;9(5):408-414.
