Optimizing ADHD Medications: What PCPs Should Know
Amit Jagtiani, MD
Child and Adolescent Psychiatrist
Youth Focus Clinic
Burrell Behavioral Health
• I have no conflicts of interest to disclose
Disclosur es
• I have no financial relationships with any manufacturers of commercial products discussed in this presentation.
Learning Objectives
Understand Executive dysfunction in ADHD
Learn Treatment options in ADHD and the evidence base
Learn How to initiate and optimize stimulants and non-stimulants
Learn Strategies to tackle common problems while prescribing ADHD medications
Understanding ADHD
A Neurodevelopmental Disorder
Childhood onset (before age 12)
Prevalence estimates in the US: ~10% in children and adolescents, 2.5% in adults
3 domains of symptoms- inattention, hyperactivity, impulsivity
DSM-5 classification in 3 types: Inattentive type, Hyperactive/Impulsive type, and Combined type
(National Health Interview Survey 2020-2022)
Understanding ADHD
ADHD as a disorder of self-regulation
• Can understand ADHD as a disorder of self-regulationfocus, motor activity, emotions
• Evolutionary resemblance to hunter-gatherers
Understanding ADHD
• New (Pathophysiological): Dopamine deficiency in frontal cortex leading to executive dysfunction
• An essential frontal lobe function
• Planning, organizing, prioritizing, and executing tasks in in efficient and timely fashion.
• Example: This meeting
What are Executive functions?
Response Inhibition Working Memory Emotional Control
Cognitive Flexibility Sustained Attention Task Initiation
Planning/ Prioritizing Organization Time Management
Goal Directed Persistence Metacognition
Executive Functions
Working Memory and Processing Speed Deficits
in ADHD
Situational Variability in ADHD Symptomatology
• Most people with ADHD have few activities where ADHD impairments are absent- anything that is interesting to the person [that gives a good dopamine boost]-video games, sports, music, Legos, etc.
• Most impairments are seen with “boring tasks”- academic work, chores, hygiene
ADHD looks like a willpower problem, but it isn’t!
ADHD: A Chemical Problem
• ADHD is fundamentally a chemical problem
• Most effective treatment is to change chemistry with medications
• Unless problematic chemistry is changed, other interventions are not likely to be very effective.
Why treat ADHD
• To reduce impairments from ADHD [academic, occupational, behavioral]
• To minimize comorbidities- learning disabilities, ODD, CD, depression, anxiety, Substance use
• To minimize interpersonal conflict within the family and with teachers
• Improve developmental trajectory of the brain
ADHD Multimod al Treatm ent Multimoda
Other Treatment Options for ADHD
• Therapy: OST, CBT, neurofeedback
• Dietary changes: food dyes, sugar, elimination diets
• Supplements/Herbs: Ashwagandha, bacopa, Ginkgo biloba, Saffron, Omega-3 FA (1-2g/d), Zinc (150 mg/d, if deficient), Magnesium, Iron
• Myth: herbs and supplements can treat ADHD (Bloch et al, 2014; AACAP practice parameters for ADHD)
What therapies are effective for ADHD?
• Effective child therapy.org – Society of Clinical Child and Adolescent Psychology
Level One: Works Well
• Behavioral Therapy (BPT, BCM)
• Organization Training
Level Two: Works
• CBT
Level Three: Might Work
• Neurofeedback
MTA study (NIMH Multimoda
l Treatment
Study of ADHD)
A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD.
Arch Gen Psychiatry. 1999 Dec;56(12):1073-86.
• METHODS:
• A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures.
• RESULTS:
• All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For core ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacherrated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period.
• CONCLUSIONS:
• For ADHD symptoms, intensive medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptoms and positive functioning outcomes.
ADHD medicatio ns
Risks with Medications
• Medications are effective in 8 out of 10 patients with ADHD.
• Medications are safe: Adverse events from stimulants are generally mild, short-lived, and responsive to dosing and time adjustments (Goldman et al. 1998)
• Common side effects: headaches, nausea, appetite suppression, insomnia, tics, “zombie” effect (emotional blunting)
• Risk of growth retardation with stimulants: Mild and Short Term: wt 1-4lbs/yr, Ht 1cm/yr for initial 2-3 yrs
• No risk of seizures unless used in very high doses.
Risks with Medications
• Risk of future substance use with stimulant use: Double risk of SUD in people with ADHD. If ADHD is appropriately treated in childhood and adolescence, risk of SUD is reduced by 84% [Wilens, Farone, Biederman, et al, 2003, Daalsgard et al., 2014]
• Risk of Dependence: No addictive potential unless inhaled or injected and when used as recommended
Risk of sudden cardiac death with stimulants
• AHA (2008) vs AAP (2008) controversy
• Current evidence: There is no compelling clinical evidence to demonstrate that the likelihood of sudden death is higher in children receiving medications for attention deficit hyperactivity disorder than that in the general population.
• Recommendation: Screening EEGs are not recommended if thorough cardiac history (including family hx) is negative.
Initiating Stimulants
General rules:
• Can choose either class…but
• Initiate ER stimulants directly
• Start low, can optimize doses weekly…but
• 70% respond to first stimulant trial; 90% respond to second stimulant trial
• Stimulants often do not follow mg/kg and effective dose is NOT based on age, weight, or severity of symptoms.
• Duration of action of a stimulant can be an important factor in choosing the medication
• Ability to swallow pills is often not a big concern in choosing medication
• Younger kids are more susceptible to side effects
ADHD response to Stimulants
•Effect Size of stimulants: approx. 1 [AMP: 1.0-1.5; MPH: 0.8-1.1]
•In Preschoolers: 0.7-1.0
Response to stimulants
Dextroamphetamine Methylphenidate Equal response to either stimulant
Role of Genetic Testing in Choosing Medications
4: Genotype may impact drug MOA [ADRA2A] and result in moderately reduced efficacy
1: Serum level may be too high, lower doses may be required [CYP2D6 intermediate metabolism]
- AMP, Viloxazine metab by CYP2D6
Pharmacokinetic Profile of IR and ER stimulants
Immediate Release
(Onset within 30 min)
Methylphenidates Amphetamines
Ritalin [MPH]: 4 hrs
Focalin [d-MPH]: 4 hrs
dextroamphetamine (Dexedrine): 4-6 hrs
D,L amphetamine (Adderall): 4-6 hrs
Extended Release
(Onset in 45-60 min)
Ritalin LA: 6-8 hrs
Metadate CD: 8hrs
Concerta: 10-12 hrs
Focalin XR: 10-12 hrs
Quillivant XR: 10-12 hrs
Daytrana patch: 9-12 hrs*
Jornay PM: 10-12 hrs**
Dexedrine spansule: 8-10 hrs
MAS (Adderall XR): 10-12 hrs
Lisdexamphetamine (Vyvanse): 1012 hrs
Dyanavel XR: 10-12 hrs
Adzenys XR ODT: 12 hrs
Xelstrym patch: 9-12 hrs* * Onset in 2-3 hrs; ** Onset after 10 hrs
Mean Plasma Concentration Curves
IR stimulants
Ritalin LA, Focalin
XR, Adderall XR
Concerta, Metadate CD
Vyvanse, Daytrana, Xelstrym
Monitoring
• Response: don’t focus on behaviors alone, monitor executive functions (task completion, chores, hygiene), classroom performance/disruptions, emotional regulation
• Side Effects: monitor vitals at each visit and compare with previous visits [Growth charts are the best]
• Timing of response and side effects
• Duration of action [ask about weekends]
• Role of Vanderbilts: Teacher vs Parent
• Role of effective communication with teachers [DRC]
• Regular ed vs Special Ed teachers
Switching Medications/Dosing
Equivalents
• No direct comparison between different ER formulations, ideally should start titration from the beginning.
• Rough equivalents: Methylphenidate 10 mg= dexmethylphenidate 5 mg
Vyvanse 30 mg= Adderall XR 10 mg
50 mg= Adderall XR 20 mg
70 mg= Adderall XR 30 mg
About 1/3rd of Vyvanse dose = d-amphetamine dose
• www.adhdmedcalc.com
Problems
Can’t Swallow pills
• Crush pills: only IR [Ritalin, Focalin, Adderall, Zenzedi (dextroamphetamine), Evekeo (amphetamine sulfate)]. Can also crush chewable ER meds
• Open capsules and sprinkle contents on applesauce-swallowed, not chewed: all ADHD meds that come as capsules that can be opened
• Dissolve capsule contents in water/juice (Prodrugs): Vyvanse, Azstarys [sardexMPH+MPH]
• Liquid formulations: Methylin [MPH IR], ProCentra [Dextroamphetamine IR], Quillivant XR [MPH ER], Dyanavel XR [AMP ER]
• Chewables: Quillichew [MPH ER], Vyvanse, Dyanavel XR [AMP-ER]
• Orally Disintegrating Tablets: Evekeo ODT [AMP sulfate], Cotempla XR-ODT [MPH-ER], Adzenys XR-ODT [AMP-ER]
• Transdermal Patch: Daytrana [MPH], Xelstrym [dextroamphetamine]
Problems:
Comorbid anxiety
• Comorbidity rated as high as 25-50%
• Risk of worsening of anxiety
• Well tolerated in many patients, ADHD treatment might improve anxiety in many people
• Stimulants alone vs Stimulants+SSRI vs Nonstimulants
Problems
Comorbid Autism Spectrum Disorders [or those with trauma/abuse/neglect hx]
• Increased risk of activation, worsened irritability/aggression, worsened anxiety
• Increased risk of side effects
• Lower response rates
• Non-stimulants preferred. Though stimulants in low to medium doses might work well
• Often polypharmacy needed (ADHD meds+atypical antipsychotics+SSRIs)
Problems:
• Comorbid substance use, risk of diversion
• Treat substance use first if it is severe, frequent, more impairing
• For ADHD: Use Vyvanse [prodrug], Daytrana/Xelstrym, Nonstimulants
• Myth: Stimulants cause dependence and increase risk of substance use
Problems:
“Meds are not working”
Higher doses are not always more effective! Dose and timing need to be carefully adjusted to each individual.
- When are they not working? (early morning, school hours/weekend mornings, later in the afternoon/evening/bus rides)
- Importance of Teacher Vanderbilt ratings
- Role of early morning or afternoon IR boosters
- BID extended-release dosing
Problems:
1. Insomnia: avoid taking late in the day 2. Irritability/Outbursts: when is it occurring? 3. Emotional Lability/Meltdowns: when is it occurring? 4. Headaches: improving hydration, waiting, PRN tylenol vs switching
Emotional blunting (Zombying effect): dose is too high, or this is not the right medication
Worsened anxiety, skin picking: switch to a non-stimulant vs adding SSRI 7. Tics: reduce dose/switch med (non-stimulants)/add on alpha agonist or antipsychotic
Problems
Appetite suppression, poor weight gain
• Calorie boosting
• Reminding to eat
• Switching meds: AMP to MPH; Longer to shorter acting, IR bid dosing
• Cyproheptadine
• Drug Holidays
Initiating and Optimizing Atomoxetine
• Start at 0.5 mg/kg for a minimum one week, then increase to 1.2-1.4 mg/kg as tolerated once daily or divided
- 10, 18, 25, 40, 60, 80, 100 mg capsules
- Cannot open capsules
• Wait 2-3 weeks on full target dose to assess potential full response
• Common side effects: nausea/appetite suppression, headache, increased HR and BP, sedation
• Qelbree (Viloxazine): 100-400 mg/d [up to 600 mg in adults]can open capsules and sprinkle
Initiating and Optimizing Alpha-Agonists
• Begin at lowest dose and titrate weekly as tolerated
- Guanfacine ER (Intuniv): 1,2,3,4 mg tabs once daily to max 4 mg/d
- Clonidine ER (Kapvay): 0.1, 0.2 mg tabs once or twice daily to max 0.4 mg/d
• Common side effects: sedation, dizziness, drop in BP [can’t skip on weekends-rebound hypertension]
• ER alpha agonists are not bioequivalent to IR pills, they are roughly 80% of IR
Third-line agents
• Bupropion
• Venlafaxine
References
• Bloch MH, Mulqueen J. Nutritional supplements for the treatment of ADHD. Child Adolesc Psychiatr Clin N Am. 2014 Oct;23(4):883-97. doi: 10.1016/j.chc.2014.05.002. Epub 2014 Aug 12. PMID: 25220092; PMCID: PMC4170184.
• A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry. 1999 Dec;56(12):1073-86. doi: 10.10 01/archpsyc.56.12.1073. PMID: 10591283.
• Goldman LS, Genel M, Bezman RJ, Slanetz PJ. Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association. JAMA. 1998 Apr 8;279(14):1100-7. doi: 10.1001/jama.279.14.1100. PMID: 9546570.
• Biederman J, Monuteaux MC, Spencer T, Wilens TE, Macpherson HA, Faraone SV. Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study. Am J Psychiatry. 2008 May;165(5):597-603. doi: 10.1176/appi.ajp.2007.07091486. Epub 2008 Mar 3. PMID: 18316421.
• Dalsgaard S, Mortensen PB, Frydenberg M, Thomsen PH. ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood - a naturalistic long-term follow-up study. Addict Behav. 2014 Jan;39(1):325-8. doi: 10.1016/j.addbeh.2013.09.002. Epub 2013 Sep 10. PMID: 24090624.