Kirstyn Kameg, DNP, PMHNP, BC Robert Morris University University Professor Objectives Describe the neurobiology implicated in the etiology of ADHD Identify the DSM-5 criteria for ADHD with an emphasis on making the diagnosis in adults Identify differences in clinical presentation of ADHD between children and adults Select appropriate rating scales to screen for ADHD in adults Identify common comorbid conditions seen in patients diagnosed with ADHD Identify pharmacologic and nonpharmacologic treatment options for ADHD ADHD Is NOT Outgrown Prevalence of ADHD
4-5% of adult US population 3.4% worldwide prevalence 1.6:1 in adults (males to females) Only 1 in 10 adults with ADHD is being treated for it; only 1 in 4 are receiving any treatment for a mental disorder
Fayyad, et al. (2007) Cross national prevalence and correlates of adult attention deficit hyperactivity disorder. British Journal of Psychiatry, 190, 402-409, De Graff, et al. (2008) The prevalence and effects of adult attention- deficit/hyperactivity disorder (ADHD) on the performance of workers: results from the WHO World Mental Health Survey Initiative. Occupational and Environmental Medicine, 65(12), 835-842. Neurobiology of ADHD ADHD is a brain-based d/o which impacts the PFC Hyperactivity is linked to the motor cortex/prefrontal motor cortex Impulsivity is linked to the orbital frontal cortex Sustained attention and problem solving are linked to the dorsolateral prefrontal cortex Selective attention is linked to the dorsal anterior cingulate cortex Arousal and ADHD Deficient arousal Individuals in a state of hypoarousal may experience inattention, cognitive dysfunction, sleepiness, and impulsivity Assoc with low tonic Da and NE firing Hyperactivity may result from an effort to combat the state of hypoarousal Meds that enhance Da and NE can increase the efficiency of information processing in the PFC and improve the sx of ADHD Arousal and ADHD (cont) Deficient arousal (cont) Pts with ADHD may also experience inefficient information processing during cognitive tasks Unable to selectively attend to a task secondary to failure to activate the ACC Meds that agonize Da 1 and/or alpha 2A adrenergic receptors allow activation of the ACC and thus pts are able to perform tasks accurately Arousal and ADHD (cont) Deficient arousal (cont) Pyramidal neurons in the PFC are “out of tune” and unable to distinguish important signals from unimportant noise Individuals are unable to focus on one thing as all the signals are the same Enhancing Da and NE neurotransmission can improve the signal-to-noise ratio and relieve these sx Arousal and ADHD (cont) Excessive arousal Some pts with ADHD have excessive arousal and can have the same sx as pts with deficient arousal PFC is “out of tune” Hyperarousal is assoc with chronic stress and may be linked to comorbidities such as anxiety, bipolar d/o, and SA Assoc with phasic firing of Da and NE Need to treat by desensitizing Da and NE receptors and steadily downregulate neuronal activity in order to reestablish normal Da and NE firing NET inhibitors and alpha 2 adrenergic agonists seem to desensitize excessive arousal sx May also help with treating comorbid anxiety and mood states assoc with ADHD Changes from DSM-IV to DSM-5 ADHD Examples have been added to the criterion items to facilitate application across the life span The onset criterion has been changed from before age 7 to 12 A comorbid diagnosis with ASD is now allowed For adults—5 symptoms instead of 6 Moved from subtypes to “presentations” DSM-5 Criteria 5/9 Inattentive Symptoms
Often: Fails to give close attention to details Difficulty sustaining attention Does not seem to listen Does not follow through on instructions Difficulty organizing tasks or activities Avoids tasks requiring sustained mental effort Loses things necessary for tasks Easily distracted Forgetful in daily activities DSM-5 Criteria 5/9 Hyperactive Impulsive Symptoms
Often: Fidgets with hands or feet or squirms in seat Leaves seat in classroom inappropriately Runs about or climbs excessively Has difficulty playing quietly Is “on the go” or “driven by a motor” Talks excessively Blurts out answers before questions are completed Has difficulty waiting turn Interrupts or intrudes on others Additional Criteria
Developmentally inappropriate symptoms 5 symptoms from either symptom list Parenthetical clarifications for adults (untested) Childhood onset Presence of symptoms prior to age 12 Treat as being flexible; Barkley, R.A. (2016) recommends age 16 Cross-setting occurrence of symptoms Significant impairment Corroboration of self-report through others Exclusion of other disorders DSM-5 Problems for Adults
Inattention list needs to be renamed or broadened Needs to include executive functioning, specifically working memory Too many hyperactive symptoms; not enough of poor inhibition/impulsiveness Symptoms are not developmentally specific Developed for children; need more appropriate items for adults (see next slide) Cutoffs are not developmentally referenced May have to adjust thresholds downward if >16 years to 4 symptoms per list Age of onset of 12 misses 7-10% of eligible adults; recall is highly unreliable Best New Symptoms for Adults
1. Often easily distracted by extraneous stimuli (DSM) 2. Often makes decisions impulsively (EF) 3. Often have difficulty stopping my activities or behavior when I should do so (EF) 4. Often start a project or task without reading or listening to the directions closely (EF) 5. Often show poor follow through on promises or commitments I may make to others (EF) 6. Often have trouble doing things in their proper order or sequence (EF) Best New Symptoms for Adults (cont) 7. Often more likely to drive a motor vehicle much faster than others (EF) For non-drivers, substitute, often have difficulty engaging in leisure activities or doing fun things quietly 8. Often has difficulty sustaining attention in tasks or play activities (DSM) 9. Often has difficulty organizing tasks and activities (DSM) Cutoff would be either 4 of first 7 or 6 of all 9 symptoms Age of onset: childhood-to-adolescence (<16 years)
Barkley, R.A. Presented at 5th Annual Conference on ADHD and Executive Dysfunction, Pittsburgh, PA, September 23, 2016
Review of Executive Functions (EF)
EFs make possible: Mentally playing with ideas Taking the time to think before acting Meeting novel, unanticipated challenges Resisting temptations Staying focused 90-98% of ADHD adults have EF deficits in daily life 35% or fewer of adults with ADHD have deficits on neuropsychological tests of EF The 5 EFs in Daily Life Activities
Self-restraint (inhibition) Cognitive, behavioral, verbal, emotional Self-management of time Consideration of past and future consequences before acting; managing self relative to time and deadlines Self-organization and problem solving Innovating, planning possible response options, rapid assembly and performance of novel goal-directed behavior Self-motivation Substituting positive goal-supporting emotions for negative goal-destructive ones Self-regulation of emotions Impairment in Adult ADHD In clinical as well as epidemiological samples compared to NCs: Learning problems (60%) Less graduated Lower education Lower income Less employed, more sickness leave More job changes (longest job 5 yrs) More often arrested, divorced and more social problems More driving accidents, teenage pregnancies, suicide attempts Higher (mental) health care costs Adult ADHD & Comorbidities
Any anxiety disorder (47%) Any mood disorder (38%) Impulse control disorder (20%) Any substance use disorders ( 15%) Symptoms of ADHD may be concealed by the more robust symptoms of these co-occurring conditions
Kessler, R.C. (2006). The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. American Journal of Psychiatry, 163(4), 716–723. Differential Diagnoses to Consider Anxiety disorders MDD Bipolar disorder Overlapping sx of poor focus, hyperactivity, impulsivity, and irritability Presence of elation, flight of ideas/racing thoughts, grandiosity, hypersexuality, and decreased need for sleep provide the best discrimination between ADHD and BP
Comprehensive Evaluation Psychiatric comorbidities Rule out potential organic D&A history etiologies Childhood and Sleep disorders; developmental history nutritional deficiencies (iron, vitamin B12, vitamin Prior assessments and D); seizure disorders; treatment thyroid dysfunction School records Cardiac history; narrow Third party report angle glaucoma; tic Obtain evidence of a disorders; recent use of chronic course of illness sympathomimetic agents without periods of remission ADHD Rating Scales for Adults Adult ADHD Self-Report Scale (ASRS) Barkley Adult ADHD Rating Scale (BAARS) Brown ADD Rating Scale for Adults Conner’s Adult ADHD Rating Scale (CAARS)-self and other Adult ADHD Self-Report Scale 18-items that reflect adult manifestations of ADHD Adopted by the WHO Available online First 6 questions correlate highly with a dx of ADHD 4/6 in shaded areas High suspicion of ADHD Most reliable with limited psych comorbidity Treatment for Adult ADHD Generally, the same medications used for children have the same therapeutic effect in adults Clinical effectiveness is sometimes less Psych comorbidities need to be considered Dose at the higher end of the FDA approved range Patients tend to use their medications PRN (during work week but may not take on weekends, vacation) Use longer acting versions Neuroprotective Effect Review of 29 studies “Despite the inherent limitations and herterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of the stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication associated brain effects may parallel, and may underlie, the well-established clinical benefits.”’ p. 902.
• Spencer, T.J. et al. (2013). Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies. Journal of Clinical Psychiatry, 74, 902-917. Stimulants and ADHD Da reuptake Once Da is released, it can be taken back into the neuron by the dopamine transporter (DAT) Once inside the cell, Da can be stored again in the synaptic vesicles via the actions of the vesicular transporter (VMAT), allowing it to be reused in subsequent neurotransmission Stimulants for ADHD (cont) Amphetamines Block DAT and NET Amphetamine is also transported into the neuron as a “hitch-hiking” substrate Inhibits Da at the VMAT thus not allowing Da to be stored in synaptic vesicles Leads to Da displacement from synaptic vesicles and increased intracellular accumulation of Da Massive amounts of Da are released into the synapse More potential for abuse Stimulants for ADHD (cont) Long-acting/extended release methylphenidate derivatives *Aptensio XR (max dose 60 mg/day) *Qullivant XR and Quillichew ER (max dose 60 mg/day) *Concerta (max dose 72 mg/day) *Focalin XR (max dose 40 mg/day) *Metadate ER (max dose 60 mg/day) Metadate CD (max dose 60 mg/day) Ritalin LA (max dose 60 mg/day) Transdermal methylphenidate (Daytrana) (max dose 30 mg/day) *FDA approved for adults Stimulants for ADHD (cont) Long-acting/extended release amphetamine derivatives *Adzenys XR ODT (max dose 18.8 mg per day) *Vyvanse (max dose 70 mg/day) * Adderall XR (max dose 30 mg/day) Dexedrine Spansule (max dose 40 mg/day) Dyanavel XR (max dose 20 mg/day) *FDA approved for adults Stimulants for ADHD (cont) Long acting preparations Occupy NET in the PFC and DAT in the NA with slow enough onset and for long enough duration to enhance tonic NE and DA signaling via alpha 2A and D1 receptors Do not occupy DAT fast or long enough in the NA to increase phasic firing Less likely to be abused Stimulants for ADHD (cont) Short-acting/immediate release methylphenidate derivatives Focalin (max dose 20 mg/day) *Ritalin (max dose 60 mg/day) Methylphenidate chewable (max dose 60 mg/day) *FDA approved in adults Stimulants for ADHD (cont) Short-acting/immediate release amphetamine derivatives Evekeo (max dose 40 mg/day) Zenzedi (max dose 40 mg/day) Adderall (max dose 60 mg/day) ProCentra (max dose 40 mg/day) Side Effects of Stimulants Most common Less common Decreased Dry mouth appetite/weight loss Dizziness Sleep problems Rebound effect Headaches Tics Jitteriness Rare Social withdrawal Stuttering Stomachaches Increased BP or HR Growth suppression Cardiovascular Risk and Stimulants Stimulants used in the rx of ADHD have not been shown to cause sudden cardiac death FDA requires stimulants’ labeling to warn about serious CV events and sudden death risk in pts with structural cardiac abnormalities The warning advises against using stimulants in adults with cardiomyopathy, serious heart rhythm abnormalities, or CAD Prior to initiating treatment with a stimulant, assess cardiovascular risk factors and pt/FHX of: Fainting or dizziness Sudden or unexpected death in someone young Sudden cardiac death or “heart attack” in family members <45 Cardiovascular Risk and Stimulants (cont) American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and the American Heart Association concur that EKG is not considered mandatory in CV assessment and monitoring during ADHD drug therapy During ADHD rx, monitor VS and refer pts with emergent cardiac sx or concerns to a cardiologist Expect small increases in BP (1-4 mm/Hg) and HR (2-6 bpm) during rx Noradrenergic Treatment of ADHD Atomoxetine (Strattera) NRI Increases both NE and Da in the PFC; does not lead to an increase of Da and NE in the NA (no abuse potential) Other meds with NRI actions utilized off-label in the rx of ADHD include: SNRIs Wellbutrin Desipramine Nortriptyline Noradrenergic Treatment of ADHD (cont) Atomoxetine (Strattera) (cont) Advantages 24 hr sx relief No abuse potential Slow-onset, long duration, and perpetual NET inhibition in the PFC, restores tonic firing and downregulates phasic NE and Da actions This reduces chronic activation of the HPA axis and can potentially reverse stress-related brain atrophy and induce neurogenesis May also reduce comorbid anxiety and depression and heavy drinking Noradrenergic Treatment of ADHD (cont) Atomoxetine (Strattera) (cont) Max dose 100 mg/day Side effects: GI upset Decreased appetite H/A Somnolence Sexual se Can elevate LFTs Can cause discontinuation syndrome Alpha 2 Adrenergic Receptor Agonists Alpha 2 receptors Present throughout the CNS including the PFC (do not have high concentrations in the NA) Believed to mediate the inattentive, hyperactive, and impulsive sx of ADHD through increasing NE release Often used as an adjunct in the treatment of substance use disorders Can be tried with chronic tic disorder Side effects: hypotension, bradycardia, fatigue, somnolence, and sedation May be helpful to treat stimulant induced insomnia Alpha 2 Adrenergic Receptor Agonists (cont)
Clonodine (Catapres) and Clonodine ER (Kapvay) Nonselective alpha agonist Binds to alpha 2A, 2B, and 2C receptors as well as imidazoline receptorscauses the sedating and hypotensive effects Guanfacine IR (Tenex) and Guanfacine ER (Intuniv) Selective for alpha 2A Reduced side effects compared to clonodine Stimulants: Basic Principles Provide psychoeducation about medication options Use FDA informed guidelines Maximize dose of stimulant before switching medication Use long acting stimulants with least abuse potential Color coded list of ADHD medications from Cohen Children’s Medical Center, Northwell Health www.adhdmedicationguide.com Consider use of adjunct non-stimulants along with stimulants before utilizing other psychotropic medications Tolerability Issues and ADHD Although ADHD meds are generally tolerated, assess for a hx of potential complications: Unstable medical condition, hyperthyroidism, glaucoma Rx with a MAOI or other pressor agent secondary to possible effects on BP and HR Use of P450 2D6 inhibitors as they can increase atomoxetine concentrations Paxil, Prozac, and Cymbalta CV disease or FHX of early cardiac disease Hx of active substance abuse problem Hx of psychosis, bipolar d/o, or an active clinically significant psychiatric comorbidity (suicidal pts or agitated pts) Why Nonstimulant Treatments for ADHD?
Problems with stimulants Schedule II drugs (abuse liability, diversion, medico- legal complications) 30% do not adequately respond or cannot tolerate stimulant treatment Short duration of action (compliance) Side effect profile can negatively impact sleep, appetite, mood and anxiety Concerns of CV effects and tic development Checklist for Improving Adherence
Educate patients Provide frequent follow Anticipated results up in early treatment Benefits and risks Strive for dose Potential long-term need optimization for Identify and treat medication/intervention comorbid conditions Possible adverse risks Typical Follow-Up Schedule and Referral
Patient with minimal risk factors Once in 3 months Provide 3 scripts with 2 of them being post-dated Date all 3 scripts today and write on the 2 other scripts, Do not fill until _/_/_ Check with patients about unfilled/remaining medications Patient with multiple risk factors Follow-up frequently (every 1-2 months) Consider referral to psychiatry/psychology for in-depth diagnostic work-up
Bangalore, S. et al. Presented at 5th Annual Conference on ADHD and Executive Dysfunction, Pittsburgh, PA, September 23, 2016 Detecting Malingering Expect malingering to be most common when a significant benefit is to be immediately obtained from the dx ADA accommodations, insurance settlements, criminal proceedings 20-25% of college students requesting ADA accommodations were found to be malingering No single, fool proof means for doing so Triangulate multiple sources of data and make comparisons Self-report, history, report from others, rating scales with population norms, archival records of impairments, clinical observations, mental status assessment, medical exam, NP testing Potential Red Flags for Misuse/Dependence Reduced effect of medication Pressure for dose escalation or request for specific drug combinations Use to manage mood, anxiety, and fatigue Personality, mood, behavioral change Suspiciousness or defensiveness Demands short-acting formulations Excessive withdrawal symptoms Overly concerned with access to medication Prescription Drug Monitoring Program (PDMP) in PA
Adopted in PA on August 25, 2016 Secure database of patients; controlled substance prescription history within the state https://pennsylvania.pmpaware.net/login Prescription Drug Monitoring Program (PDMP) in PA (cont)
New patient with ADHD as part of reviewing records Any suspicion if a patient is abusing or diverting controlled substance Initiating a prescription for a controlled substance (schedule II-IV) Changing from one controlled substance to another, even in the same class Document in medical record that the PA PDMP program was monitored during the process Psychosocial Recommendations Psychoeducation about ADHD Chronic disability perspective is essential CBT training of executive functioning Emphasis on cognitive distortions Failure, incompetence, insecurities Assistance with time management and organization Use of planners, lists, charts, and other organizational devices Create filing systems Assist in reducing distractability Break tasks into smaller quotas; use timers Psychosocial Recommendations (cont) Psychoeducation should include driving risks Recommend: Longer time of having learner’s permit Graduated driving approach NO cell phone while driving Block cell signal while car is running Cellcontrol.com ($129 for 1 car) Apple and android phones Psychosocial Recommendations (cont) More on driving psychoeducation Greater supervision of vehicle use by parents Random spot checking on destinations GPS car monitoring devices (Mobile Teen GPS; MOTOsafety) http://www.consumerreports.org/cro/magazine/2014/07/how-to- track-your-teen-driver/index.htm Behavior contracting for safe driving Russell Barkley—A Safe Driving Program Maureen Snyder—ADHD and Driving Use medication mgmt. XR plus IR later in day NO alcohol! When to Refer? Symptoms still impairing after 2-3 trials of FDA approved stimulants and a non-stimulant with adequate dosing Persisting life difficulties despite adequate med mgmt Sleep problems Multiple comorbidities and SA Resources For providers: American Professional Society of ADHD and related disorders https://apsard.org/ Free training videos (with CEU credit) http://naceonline.com/APSARD-CME-Courses/catalog.php Adult ADHD Self-Report Scale (ASRS) Symptom Checklist https://add.org/wp-content/uploads/2015/03/adhd-questionnaire-ASRS111.pdf For patients: Children and Adults with ADHD (CHADD) http://www.chadd.org/ Attention Deficit Disorder Association (ADDA) https://add.org/ American Academy of Child and Adolescent Psychiatry (AACAP) http://www.aacap.org/AACAP/Families_and_Youth/Family_Resources/Home.asp x