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 symptomsinstead 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 D&A history Childhood and

developmental history Prior assessments and

treatment School records Third party report Obtain evidence of a

chronic course of illness without periods of remission

Rule out potential organic etiologies Sleep disorders;

nutritional deficiencies (iron, vitamin B12, vitamin D); seizure disorders; thyroid dysfunction

Cardiac history; narrow angle glaucoma; tic disorders; recent use of sympathomimetic agents

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

Decreased appetite/weight loss

Sleep problems

Headaches

Jitteriness

Social withdrawal

Stomachaches

Less common

Dry mouth

Dizziness

Rebound effect

Tics

Rare

Stuttering

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

Anticipated results

Benefits and risks

Potential long-term need for medication/intervention

Possible adverse risks

Provide frequent follow up in early treatment

Strive for dose optimization

Identify and treat comorbid conditions

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