First, Do No Harm: Practical Strategies for Helping Adults with ADHD in Primary Care

1. First, Do No Harm: Practical Strategies forHelping Adults with ADHD in Primary Care Leslie Walker MD Case Western Reserve University Dept. of Psychiatry April 2019

2. Objectives • Learn differential dx of inattention and hyperactivity in adults. • Learn typical trajectory of ADHD from childhood into adulthood. • Learn the three classes of FDA-approved medications for treatment of ADHD. • Learn basic principles for determining risks vs. benefits for both medication and non-medication strategies for adult ADHD.

3. 1961 Ritalin approved for children • 1982 Ritalin SR approved for children • 1994 Driven to Distraction • 1996 Adderall approved for ADHD without any clinical trial data • 2002 Strattera approved for kids & adults • 2004 Adderall XR added adults to FDA approval • 2008 Concerta added adults, Vyvanse approved for both kids & adults

4. Diff Dx of Adult Inattention + Hyperactivity • Mood Disorders (10-20%) • Major Depression, Bipolar Disorder • Anxiety Disorders (13%) • Psychotic Disorders (2%) • Acute and sustained trauma • TBI, Intellectual disability, Autism • MCI/Dementia • Bereavement • ADD/ADHD (4.4%) • Sleep deprivation/disorders • Hearing loss • Medical/neurological conditions • Medications • Drug intoxication • Drug withdrawal • Delirium • Malingering

5. Adult ADD is highly comorbid with other dx • Of 18-44 year olds with ADHD: • 38% also had a mood disorder in past 12 mos. • 18.6% had MDD • 19.4% had bipolar disorder • 47% also had an anxiety disorder including PTSD • 8% had GAD • 12% had PTSD • 29% had social phobia • 15% also had a substance use disorder (from the NCS study Kessler using DSM-IV, Am J Psych, 2006) • Without ADHD: • 11% had a mood dx • 8% had MDD • 3% had bipolar dx • 19% had anxiety dx • 3% had GAD • 3% had PTSD • 8% social phobia • 6% had a SUD

6. Critical Elements of Psychiatric History • PPH: Mood episodes/anxiety/psychosis in past? Prior dx/tx of ADHD? • HPI: When did current symptoms start? When was patient last well? CHRONOLOGY of inattentive symptoms? Did sleep/mood/motivation change at the same time? Any medical/medication changes? • FH: Mood disorders, psychosis, substance abuse, dementia, ADHD • SH: Childhood LD/school performance/behavioral issues, Educational hx, Work hx, Relationship hx, Substance Use hx, Legal hx

7. ADD/ADHD is a clinical diagnosis • Screening scales • Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist • “Computer testing” ieConners Continuous Performance Test • 4 domains: inattentiveness, impulsivity, sustained attention, vigilance • IQ Testing or Neuropsych testing (Memory, Executive Functioning) • There is no test, scan, or computer that can diagnose ADD. An experienced clinician has to take the time to obtain useful clinical information from the patient and ideally an outside informant.

8. DSM-5 ADHD Criteria • Persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. • Symptoms have been present before age 12, for at least 6 months, are inappropriate for developmental level, occur in 2+ settings, interfere with social, school, or work functioning, and are NOT better explained by another mental disorder. • Two sets of symptoms: Inattention and Hyperactivity/Impulsivity so patients can be diagnosed (based on 5+ symptoms in last 6 months) with: • ADD Inattentive Type (ADD-I) • ADHD Hyperactive/Impulsive Type • ADHD Combined type

9. HYPERACTIVITY & IMPULSIVITY: OFTEN • Often fidgets with/taps hands or feet. • Often leaves seat in situations where expected to remain seated. • Often feels restless or has to move in inappropriate situations. • Often unable to take part in leisure activities quietly. • Often “on the go,” acting as if “driven by a motor.” • Often talks excessively. • Often blurts out an answer before a question has been completed. • Often has trouble waiting his/her turn (ie lines, traffic) • Often interrupts/intrudes on others (ie butts into conversations).

10. Inattention symptoms: OFTEN • Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or with other activities (ie driving). • Often has trouble holding attention on tasks (ie business presentation). • Often does not seem to listen when spoken to directly. • Often is easily distracted (ie even during a conversation).

11. Inattention symptoms: OFTEN • Often does not follow through on instructions and fails to finish schoolwork, chores, or workplace duties. • Often has trouble organizing tasks and activities. • Often avoids, dislikes, or is reluctant to do tasks that require mental effort over a long period of time (ie big projects, taxes).

12. Inattention symptoms: OFTEN • Often loses things necessary for tasks and activities (ie school/work materials, wallets, keys, credit cards, glasses, cell phones). • Often is forgetful in daily activities (ie forgets to go to appointments, turn in assignments, pay bills).

13. Typical Trajectory • Gender • Boys are more likely to have HI or combined subtype • Girls more likely to be inattentive • M:F ratios in ADHD • Childhood 8:1 • Adolescents/Adult: 4:1 • Community Samples: 2.5:1 • HI symptoms tend to diminish by adolescence • Executive function symptoms tend to become more prominent and disabling in young adulthood • Adults are most likely to have inattentive subtype

14. Executive Functions: Essential for Independence • Planning • Prioritizing • Sequencing • Organizing • Judgment • Multi-tasking

15. Neuroscience of ADHD • Dopamine (DA) and Norepinephrine (NE) modulate attention, behavior, and emotion in the prefrontal cortex (PFC) • PFC typically matures by age 25, may be delayed in ADHD

16. Common Symptoms in Adult ADD • Inattentiveness • Losing things • Forgetting things • Not recording/remembering deadlines • Careless errors • Missing social cues • Easily bored/distracted • Hyperfocus • Poor executive function • Procrastinating/difficulty initiating tasks • Inability to break down complex tasks into smaller chunks • Lack of time awareness & poor time management • Poor judgment regarding which tasks are most important • Difficulty organizing and maintaining space/information

17. Stepwise Evaluation & Treatment • Differential dx: List potential contributors to attention problems. • Taper off sedating meds; refer for substance abuse treatment if needed. • Cognitive screen for adults over 50 presenting for the first time with attention complaints or executive dysfunction. • Treat mood, anxiety, sleep, and medical disorders first. • Once optimized, re-evaluate attention/focus/executive functions: • Childhood functioning/impairment? • Current functioning/impairment?

18. Non-medication strategies: ADD Coaching • Increase structure • Standard Operating Procedures (SOPs) • Time management technology (alarms) • Delegate executive functions • Choose less sedentary/boring careers, adventurous hobbies

19. Informed consent for medication tx

20. Risks of untreated ADHD? • Worse school performance, fewer advanced degrees • Reduced work advancement, reduced income • Increased rates of divorce by 2x • Increased risk of SUDs by 2.5x • nicotine dependence (2x), alcohol abuse/dependence (2x), MJ dependence (1.5x), cocaine dependence (2x). (Lee, Neuropsychiatry, 2012) • Increased risk of MVAs • 44% (women) to 49% (men) more likely to have a crash over a 10-year period (JAMA Psychiatry 2017)

21. Benefits with ADHD treatment • Improved focus/concentration • Improved task completion • Improved school/work performance • Improved relationships

22. Benefits with ADHD treatment • Reduced risk of substance abuse and incarceration • Reduced risk of MVAs • 10-year study, n >2 million, 11000 (0.5%) had crashes. (JAMA Psychiatry, 2017) • Compared to people without ADHD, patients with ADHD dx were 44% (women) to 49% (men) more likely to have a crash. • Risk of crash dropped by 38% (men) to 42% (women) during months when they received a stimulant Rx. • Estimate: 22% of crashes could have been prevented if meds used.

23. 3 classes of medications • Stimulants: increase synaptic dopamine (DA) & norepinephrine (NE) • Methylphenidate (MPH)(Ritalin) group – block DA and NE reuptake • Mixed amphetamine salts (Adderall) group – stimulate DA & NE release and block DA and NE reuptake • Atomoxetine (Strattera): selective NE reuptake inhibitor (NRI) • Alpha 2-agonists: stimulate presynaptic NE receptors, ↓ sympathetic tone • Clonidine (Kapvay) • Guanfacine (Intuniv)

24. Stimulant POSSIBLE SIDE EFFECTS & RISKS • CV: elevated BP and HR • No elevated risk of MI, CVA, sudden cardiac death in large EHR study when daily stimulants or atomoxetine was prescribed to 150K healthy 25-64 yo adults at appropriate doses. (Habel, JAMA 2011) • GI: Nausea, abd pain, loss of appetite, weight loss.

25. Stimulant POSSIBLE SIDE EFFECTS & RISKS • Neuro: tremor, muscle tension, jittery feeling, headache, insomnia. • Psych: anxiety, panic attacks, switching to mania/hypomania or more rapid cycling, irritability, agitation, psychosis, acute depression or irritable “crash” when stimulant wears off, dependence/withdrawal/cravings. • Legal: diversion, selling, meds being stolen.

26. Stimulants? First, Do No Harm • Contraindications to stimulants • Current/past stimulant abuse • CAD/arrythmia/uncontrolled HTN • Hypertensive CVA • History of psychosis • MAOIs • Relative contraindications • Current/past substance abuse • High risk of substance abuse • High risk of psychosis (ie cannabis user, FH of psychosis) • Tic disorders • Glaucoma • Uncontrolled anxiety • Taking daily benzodiazepines or other significantly sedating daytime medications

27. Baseline • OARRS • BP, HR, weight. Consider EKG. • Safe storage plan and risk assessment for diversion • Stimulant policy/contract • Lost prescription/medication policy • Minimum frequency of in-person appointments and/or bp checks • Intermittent urine tox screens • Careful psychiatric and cardiovascular warnings

28. Choosing a stimulant: • Delivery method: • Oral • Plain or layered tablets • Osmotic capsules • Beads in capsules • Chewable • Liquid (immediate and delayed) • Transdermal patch • Onset: • Immediate • Immediate & delayed • Delayed • Duration: • Short (up to 4h) • Intermediate (6-8h) • Long (12-16h)

29. FDA-approved (some not studied in adults) • Strattera (NDRI, takes a few weeks to take effect, then 24h effect) Methylphenidate (MPH) Stimulants: • Concerta (OROS technology: 20% immediate, the rest over 8-12h) • Focalin XR (beads, 50% immediate release, 50% delayed release) • Metadate CD (beads, 30% immediate release, 70% delayed release) • Quillivant XR (liquid, 8-12h) • *Jornay PM (qhs dosing, 50% released after 10h, 50% later in day) Amphetamine Stimulants: • Adderall XR (10-12h) & *Adzenys (12h) (50% immediate, 50% delayed) • Mydayis (16h) (3 phases: immediate, delayed, late release) • Vyvanse (12-14h) (cleaving technology, gradually available after 1-2h)

30. Medication choice in adults? • Everyone gets coaching, resource referrals. • Atomoxetine to start, particularly in patients with history/risk of substance abuse or psychosis. • If ineffective, stimulants next if not contraindicated. • Establish a long-acting agent dose/tolerability/effectiveness. • If needed, consider a prn immediate-release dose for evening. • Consider adding/substituting an alpha-agonist if stimulants are not tolerated, persistent difficulty settling down to sleep at night, persistent hyperactivity, comorbid trauma/hypervigilance.

31. Off-label options in adult ADD • Off-label: consider buproprion SR/XL (NDRI) if comorbid depression and/or history or high risk of substance abuse. • Farther off-label: TCAs imipramine or desipramine (NDRIs) or nortriptyline (NRI) if comorbid depression, insomnia, but higher arrythmia risk. • Many ADHD medications have not had RCTs in adults, so we don’t have specific safety/side effect information.

32. Follow-up evaluations • BP/HR and weight • ADD symptom re-evaluation • Mood, psychosis, anxiety, sleep re-evaluation • Side effect review • Storage strategy and risk evaluation/availability to others in the home • Consider intermittent urine screens • (+) Amphetamine can be false positive for other drugs • 5-drug basic tox screens won’t pick up MPH; order a specific MPH + metabolite screen • Avoid/screen for new sedating medications that interfere with focus/concentration or block dopamine

33. Stimulant tolerance • Regular use usually does not reduce benefits for ADHD sx. • Tolerance develops to most side effects (nausea, jitteriness) and energy boost. • Repeated use of stimulants to get high results in tolerance, requiring higher doses over time, increasing cardiovascular risks, deceasing appetite and weight, and impairing function.

34. Stimulant withdrawal • Lethargy/fatigue. • Increased sleep or insomnia. • Depression or mood swings. • Increased appetite. • Intense drug cravings. • Not life-threatening. Inpatient detoxification is not medically required unless the patient has other comorbid conditions which put them at risk.

35. Diversion/abuse risks • Appropriate ADHD treatment with stimulants does not appear to increase the risk of subsequent drug addiction and may lower it (Chang et al, J Child Psychol Psychiatry 2014) • 5-10% of HS students and 5-35% of college students reported using unprescribed stimulants, but 71% reported having a peer who used unprescribed stimulants (Clemow & Walker, Postgrad Med, 2014) • Medical professionals may be at particular risk for prescription medication abuse, particularly if they used unprescribed stimulants during education/training • Immediate release crushable tablets may be easiest to abuse, but all stimulants can be abused

36. Resources • ADDitudemag.com • CHADD.org – Children and Adults Living with ADD • Attention Magazine • ADDadult.com • David Goodman MD at Hopkins • Nice list of celebrities with ADHD

37. www.LeslieWalkerMD.com