Identification and Management of Attention-Deficit / Hyperactivity

Identification and Management of

Attention-Deficit/Hyperactivity Disorder

(ADHD) in Adults

Academic Detailing Clinician Guide

Contents

Background 1

Clinical manifestation in adults 2

Assessment and diagnosis 6

Stepped diagnostic procedure for ADHD in adults 8

Treatment 10

Before starting ADHD treatment 11

Pharmacotherapy for ADHD in adults 12

Non-pharmacologic treatment

Monitoring, follow-up, and continued care 16

Supporting people with ADHD

References 20

These materials were developed by:

VA PBM Academic Detailing Services

Your Partner in Enhancing Veteran Health Outcomes

VA PBM Academic Detailing Services Email Group:

PharmacyAcademicDetailingProgr[email protected]

VA PBM Academic Detailing Services SharePoint Site:

https://dvagov.sharepoint.com/sites/vhaacademicdetailing

VA PBM Academic Detailing Services Public Website:

http://www.pbm.va.gov/PBM/academicdetailingservicehome.asp

U.S. DEPARTMENT OF VETERANS AFFAIRS

Background

Attention-Deficit/Hyperactivity Disorder (ADHD) is typically a chronic, often lifelong,

neurodevelopmental disorder.

The approach for diagnosing and treating Veterans with ADHD

involves an individualized clinical assessment which should include consideration of risks and

benefits for both treating and not treating the disorder.

DID

YOU

KNOW

Prescription stimulants are considered first-line treatment for ADHD

and have been shown to improve symptoms and outcomes.

–

Untreated ADHD has been associated with increased morbidity and mortality

as well as decreased social, educational, vocational, and self-care functioning.

Treatment of ADHD with stimulants has not been associated with an

increased risk of substance use disorder (SUD).

–

A meta-analysis of 15 longitudinal studies of patients with a history of stimulant-

treated ADHD vs. matched cohorts without treatment found no association

between treatment and subsequent substance use, abuse, or dependence.

–

In adolescents, treating ADHD with stimulants has been found to either

lower the risk of SUD or have no impact on SUD risk.

3-5

Stimulant overdose deaths are primarily driven by cocaine and

methamphetamine, not prescription stimulants.

Figure 1. The diagnostic criteria for the condition now known as ADHD have evolved as

research has furthered our understanding of the characteristics of the disorder.

1,7-10

DSM-II:

Hyperkinetic

Reaction of

Childhood

Disorder

DSM-III:

Revised to

include

cognitive/

attentional

aspects (ADHD)

DSM-IV:

ADHD with

3 subtypes

(inattentive,

hyperactive-impulsive,

combined)

DSM-5:

Added examples

of manifestation

in adults;

subtypes changed

to presentations

ADHD

recognized

worldwide as a

lifespan disorder

1968

1980

-87

1994 2013 Today

“Like many psychiatrists, we began our medical and psychiatric training

in the last century. We were taught that patients with adult

attention deficit/hyperactivity disorder (ADHD) had a dubious diagnosis

and were probably seeking stimulants for nefarious purposes.”

— Dr. Josh Geffen

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

FAST FACTS

• 45-70% of childhood cases persist into adulthood.

1,13-15

–

More recent data suggest that > 90% of childhood cases

have residual, sometimes fluctuating, symptoms and

impairments through at least young adulthood.

• Estimated prevalence rate is about 4.4-5.2% in U.S. adults.

14,17

–

In military samples, estimated prevalence rates range

between 5.8–9%.

12,15

• Highly heritable: parents with ADHD have a > 50% chance

of having a child with ADHD.

In nondeployed U.S.

Army personnel, the

estimated 30-day

prevalence for ADHD

was found to be 7.0%.

Only 2 disorders were

higher, intermittent explosive disorder

(11.2%) and PTSD (8.6%).

Clinical manifestation in adults

ADHD is characterized by a persistent pattern of attention deficit, hyperactivity, and/or

impulsivity that pervades across a variety of settings and results in functional impairment.

7,9,20,21

• Although onset occurs in childhood, ADHD is

not necessarily diagnosed at that time.

• The clinical manifestation is heterogeneous,

with different levels of severity and prevalence

of each core symptom.

22-24

• Symptoms may wax and wane due to changing

life circumstances, functional expectations,

and/or comorbid conditions.

• Some may experience a reduction or remission

of symptoms, particularly hyperactivity,

with age.

20,24,26

• Approximately 30-70% of adults with ADHD have emotional dysregulation (e.g., mood lability,

irritability, anger outbursts, low frustration tolerance, motivational deficits).

7,20,27,28

• Dysfunctional strategies (e.g., drinking alcohol, smoking cannabis) may be used to cope with

emotional turmoil, social isolation, and rejection.

• People with ADHD often identify positive aspects such as creativity, enthusiasm, awareness of

the multiplicity of things, and the ability to hyper-focus and multitask when interested in a topic.

Focus with ADHD “feels like a short

wave radio that most of the time can’t

find the right frequency.”

DID

YOU

KNOW

People with ADHD are unable to distinguish important

neuronal signals from unimportant ones. This results in

challenges focusing on one thing more than another.

U.S. DEPARTMENT OF VETERANS AFFAIRS

Gender differences

• ADHD is thought to be underrecognized

and underdiagnosed in females with

implications for long-term social, educational,

and health outcomes.

29-31

• Females are more likely to be diagnosed with

predominantly inattentive ADHD.

29,32,33

–

Inattention in girls and women with ADHD may

present as being easily distracted, disorganized,

overwhelmed, and lacking in effort or motivation.

• In females, symptoms are typically pervasive and impairing rather than

transient or fluctuating.

• Hyperactive-impulsive symptom severity may be lower in females than

in males and/or may be more verbal (e.g., interrupting others, talking

excessively, frequently changing topics).

• Difficulties with emotional lability and emotional dysregulation may

be more severe or common in girls and women with ADHD.

• Social problems may be particularly impairing.

• ADHD symptoms may become more obvious later in females, often during

periods of social or educational transition.

• Adult women may develop awareness of their difficulties leading them to seek services.

Females with undiagnosed ADHD

are more likely to receive a primary

diagnosis of internalizing disorders

(e.g., anxiety, depression) or

personality disorders.

This delays diagnosing ADHD and

accessing appropriate treatment.

Figure 2. ADHD is associated with increased mortality, and mortality is higher for women

compared to men.

Mortality rate per

10,000 person-years

Women with ADHD

without select

comorbidities

Men with ADHD

without select

comorbidities

A Danish nationwide cohort study estimated

Mortality Rate Ratios (MRRs) in 1.92 million

individuals, including 32,061 with ADHD,

for 24.9 million person-years.

Girls and women with ADHD without

oppositional defiant disorder, conduct

disorder, or substance use disorder had a

2.85x (95% CI = 1.56-4.71) higher risk

of death than women without the

4 disorders.

This was more than double the 1.27x

(95% CI = 0.89-1.76) higher risk of death

in boys and men.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Gender and symptom severity have been shown to influence suicidal thoughts.

According to one study, the likelihood

of suicidal ideation was significantly

higher in women with ADHD compared

to controls. There was also a statistically

significant positive association between

the likelihood of suicidal ideation and

symptom severity (4 of 4 Conners’ Adult

ADHD Rating Scale [CAARS] subscales

in females).

Figure 3. Odds ratios for suicidal ideation for a

one-point increase in severity on each item on

the four CAARS subscales

Male

Female

Odds ratio for suicidal ideation

Inattention

Hyper-

active

Impulsive Problems with

self-concept

ADHD is a chronic health problem with significant risk for mortality

and long-term morbidity in adulthood.

People with ADHD may live with unrecognized symptoms from childhood

(median age of 6) to adulthood (up to the median age of 25) for a median

time-lag of 17 years without treatment.

Almost every aspect of adult life can be impacted by ADHD, particularly if the condition

remains undiagnosed, untreated, or ineffectively treated.

1,7,22-24,30,32,35-39

Health problems

• Suicidality (completions,

attempts, and ideation)

• Development of comor-

bidities (e.g., mood, sleep

difficulty, anxiety, SUD)

• Obesity and overeating

High-risk behavior

consequences

• Delinquency and crime

• Motor vehicle accidents

• Risky driving, more

speeding tickets

• Unplanned pregnancies

• Sexually transmitted

infections

Relationship and work

challenges

• Lower educational and

occupational achievement

• Financial problems

• Diminished social

functioning

• Divorce

U.S. DEPARTMENT OF VETERANS AFFAIRS

Screening tools: your tool to guard against missing a comorbidity

Adults with undiagnosed ADHD may seek treatment for what seems like a primary mood, anxiety,

or other mental health disorder. Others may get medical attention for substance use or high-risk

behavior consequences (e.g., motor vehicle accidents, unplanned pregnancies).

1,19

It is important to know when to screen for underlying ADHD.

Missing a diagnosis of ADHD can result in years of trials with antidepressants,

mood stabilizers, and anxiolytics without adequate symptom response.

Example screening opportunities

A patient seeking an assessment for ADHD with no prior diagnosis. This may happen if:

–

Someone close to the patient learned about ADHD and recognized the traits.

–

The patient learned about ADHD and recognized the relevant symptoms.

–

A relative was diagnosed with ADHD, triggering an awareness of ADHD

(e.g., child is diagnosed).

The patient has symptoms attributed to another psychiatric diagnosis

(mania, depression, anxiety) but is not responding as expected to treatment.

There are functional difficulties such as attention problems, academic issues,

time management, driving, or marital problems and the clinician postulates ADHD

as a possible explanation.

ADHD screening tools can be used to help determine the probability that someone

has the disorder.

However, “just as a thermometer records a fever but does not identify the

many reasons it could be occurring, ADHD symptom scales do not tell you if ADHD is the specific

reason the symptoms are occurring.”

A mental health evaluation that includes a detailed

developmental history should be performed on those who screen positive.

DID

YOU

KNOW

Transitioning from military to civilian life may disrupt behavioral support

and coping mechanisms relied on by those with undiagnosed ADHD.

Studies suggest the discipline of a highly structured context (e.g., military)

provides an environment for those with ADHD to develop organizational skills.

Routine physical training, exercise, and use of substances (e.g., caffeine) are

thought to reduce at least some ADHD symptoms.

Use ADHD screening tools to identify potential cases of ADHD in need of further evaluation.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Assessment and diagnosis

The clinical interview and evaluation continues to be the mainstay of ADHD diagnosis.

Use the DSM-5-TR diagnostic criteria for ADHD to guide your clinical assessment of the patient.

7,10,20,42

Table 1. Linking diagnostic criteria with adult manifestations of ADHD

7,20

INATTENTION (5 or more for adults)

DSM-5-TR Criterion A for ADHD* Example behaviors**

Possible signs (self-report or

coping mechanisms)

Often fails to give close attention to

details or makes careless mistakes in

schoolwork, at work, or during other

activities

Overlooks or misses details, work is inaccurate

• May use substances (e.g.,

caffeine, nicotine, alcohol)

to mitigate symptoms

• Fatigued from energy

required to sustain tasks

• Interpersonal problems

• Forgetful

• Poor or underdeveloped

reading/verbal skills

• Problems learning new

material

• Relies on others to

remind them of tasks

• Avoids reading books

or activities that require

sustained attention for leisure

• Has a hard time completing

activities that require

sustained attention

• Works harder than others

to perform

• Establishes structure/routines

to increase capacity to

complete tasks

Often has difficulty sustaining attention

in tasks or play activities

Has difficulty remaining focused during lectures,

conversations, or lengthy reading; has difficulty

making decisions

Often does not seem to listen when

spoken to directly

Mind seems elsewhere, even in the absence

of any obvious distraction

Often does not follow through on

instructions, does not finish schoolwork,

chores, or duties

Starts tasks but quickly loses focus and is easily

sidetracked; procrastinates

Often has difficulty organizing tasks

and activities

Difficulty managing sequential tasks, keeping

materials/belongings in order; messy,

disorganized work; poor time management;

misses deadlines

Often avoids, dislikes, or is reluctant to

engage in tasks that require sustained

mental effort

Avoids, dislikes, or is reluctant when preparing

reports, completing forms, or reviewing lengthy

papers

Often loses things necessary for tasks

or activities

Loses tools, wallet, keys, paperwork, eyeglasses,

mobile telephones

Is often easily distracted by extraneous

stimuli

Easily distracted; has unrelated thoughts

Is often forgetful in daily activities Forgetful when doing chores/running errands; forgets

to return calls, pay bills, attend appointments

5 or more symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and

that negatively impacts directly on social and academic/occupational activities.

Example behaviors should be “often.”

U.S. DEPARTMENT OF VETERANS AFFAIRS

HYPERACTIVITY AND IMPULSIVITY (5 or more for adults)

DSM-5-TR Criterion A for ADHD* Example behaviors**

Possible signs (self-report or

coping mechanisms)

Often fidgets with or taps hands/feet

or squirms in seat

Restless, unable to sit still • Reports frequent

interpersonal conflict

• Reports needing exercise

or substances as a coping

mechanism to manage

symptoms

• Feels misinterpreted by others

• Impulsively blurts out

inappropriate comments

• Feels less connected to others

due to frequent conflict

• Describes their actions/

verbalizing thoughts as

‘‘ready, fire, aim’’

• Reports difficulty keeping friends

or meeting new people

• Reports partner, friends, and/or

family say they feel neglected

or unimportant

• Has difficulty following rules

(e.g., criminal history, speeding

tickets)

• Reports difficulty with social cues

Often leaves seat in situations when

remaining seated is expected

May avoid situations/places that require remaining

in place (e.g., movie theaters, standing in line)

Often runs/climbs in situations where

it is inappropriate

Feeling restless; may tend to choose very

active jobs

Often unable to play or engage in

leisure activities quietly

Constant activity; avoids activities that require

staying quiet or inactive (e.g., yoga, meditation)

Is often “on the go,” acting as if

“driven by a motor”

Is unable/uncomfortable being still for extended

time; may be experienced by others as being

restless/difficult to keep up with

Often talks excessively Long-winded responses (may be perceived by

others as talking too much or all the time)

Often blurts out an answer before

a question has been completed

Verbal impulsivity; completes people's sentences;

cannot wait for turn in conversation

Often has difficulty waiting his

or her turn

Difficulty waiting in line/for others to finish,

overreacting to frustrations

Often interrupts or intrudes on others Interrupts conversations/activities;

may intrude/take over things

5 or more symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and

that negatively impacts directly on social and academic/occupational activities.

Example behaviors should be “often.”

“I guess everyone has ADHD

because everyone is inattentive

sometimes, especially these days.”

While the symptoms of ADHD can

occur in everyone occasionally

(e.g., forgetting items), people

with ADHD experience significantly

greater numbers of symptoms

(≥ 5 for adults) with greater

frequency and more significant

difficulties and impairment.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Stepped diagnostic procedure for ADHD in adults

7,10

An “ideal” or “gold standard” adult ADHD evaluation should include a clinical interview, a structured/

semi-structured interview, informant reports/collateral information, assessment of impairment,

and evaluation of alternative symptom sources.

If malingering (intentionally feigning or exaggerating symptoms for personal gain) is suspected,

consider providing or referring the Veteran for a psychological assessment that includes use of

symptom and performance validity measures. Informant and objective records can be used to

verify self-reports.

See QRG

Please see the ADHD Quick Reference Guide (QRG) for more information on

stepped diagnostic procedure.

STEP

Assess each of the eighteen DSM-5-TR ADHD symptoms to ensure 5 or more are

present for at least 6 months.

Combining self- and informant-reported symptoms

is the most effective way to establish the A-criterion. Although rating scales alone

are not sufficient to diagnose ADHD, using them as a part of the evaluation is widely

recommended.

STEP

Establish chronicity (several symptoms present prior to age 12) and contextual

stability (several symptoms are present in 2 or more settings).

A complete

childhood developmental history is an important part of a comprehensive assessment.

Note: Diagnosis of ADHD does not require uninterrupted symptoms since childhood.

9,10

STEP

Establish clinically significant impairment.

The impact of ADHD is best judged

by considering the level of impairment, pervasiveness, and familial and social context.

There should be clear evidence that the symptoms interfere with or reduce quality

of functioning.

CLINICAL PEARL

Assessing the effect of ADHD symptoms on impairment and quality of life should include an assessment of the broader

range of problems linked to ADHD (e.g., executive function impairments, sleep problems, irritability, internal

restlessness) in addition to functional impairments (e.g., traffic accidents, occupational underachievement).

As with many mental health disorders, even minor levels of symptoms can cause considerable distress to individuals

because of the chronic and persistent nature of symptoms.

Focus on subjective accounts of mental state

phenomena, as with someone who reports feeling depressed, experiencing a panic attack, or hearing a voice.

U.S. DEPARTMENT OF VETERANS AFFAIRS

STEP

Rule out other causes of symptoms: differential diagnosis.

10,20

A thorough ADHD

evaluation typically includes a physical examination, necessary tests, and review of medical

history to rule out other causes of symptoms—e.g., post-traumatic stress disorder (PTSD),

traumatic brain injury (TBI), SUD, sleep disorders, anxiety, and depression.

–

ADHD as a diagnosis may be eliminated if symptom onset is simultaneous with

the onset of a separate physical or mental disorder, or if symptoms solely occur

during substance use, medical problems, or other mental health disorders.

–

One clear distinction of ADHD is the typical early onset and trait-like

persistence of ADHD symptoms.

STEP

Finalize diagnosis.

If the patient meets DSM-5-TR criteria for ADHD, determine presentation (e.g.,

predominantly inattentive) and severity (mild, moderate, severe) to finalize the diagnosis.

Clinical pearl:

When making a first-time ADHD diagnosis in adulthood, consider

documenting factors that may have prevented childhood diagnosis.

Support after diagnosis

Following a diagnosis of ADHD, have a structured discussion with the patient about ADHD and

provide support (include families/caregivers as appropriate). This could include:

24,31

Improving understanding of symptoms and how ADHD

may affect relationships and functioning

Identifying and building on individual strengths

Facilitating access to services

Modifying the environment to reduce the impact of ADHD

symptoms; use of electronic devices to provide reminders, track to-do lists, etc.

Understanding the importance of structure in daily activities

Increasing understanding of how ADHD may impact career choices and rights to reasonable

accommodations in the workplace and/or school

Recognizing the increased risk of substance misuse/use disorder

Adults who screen positive for ADHD should receive a

mental health assessment to evaluate for ADHD.

1,31

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Treatment

ADHD requires a comprehensive, collaborative, and multimodal treatment

approach tailored to meet the unique needs of the person with ADHD.

It is important to clearly identify all areas of impairment due to ADHD at the

onset of treatment and regularly re-evaluate the impact of the condition.

Pharmacotherapy is first-line treatment for ADHD in adults

to target core symptoms causing impairment.

1,9,11,20,21,28,31,44,46-49

–

Psychostimulants: amphetamines, methylphenidate

–

Non-stimulants: atomoxetine

Non-pharmacological interventions for adult ADHD can

play an important role in helping adults manage and

understand their condition.

46,50,51

DID

YOU

KNOW

According to a

study in a nationally

representative

sample of adults in

the U.S., only 10.9%

of respondents with

adult ADHD received

treatment for ADHD

in the 12 months

before interview.

Treatment outcomes

Patients with ADHD who receive treatment (by any modality) have better long-term outcomes

than their non-treated counterparts across most studied domains.

25,44,52-56

Examples include:

• Reduced suicidal ideation and attempts

• Reduced likelihood of motor vehicle accidents

• Reduced criminal behavior

• Higher self-esteem and social functioning

Figure 4. ADHD treatment improves outcomes, compared with untreated ADHD.

reated participants with ADHD

benefit

Treatment benefit by outcome group

Outcomes in each

outcome group

20%

60%

Driving

Obesity

Self-esteem

Social function

Academic

Drug/Addictive

Antisocial

Services use

Occupation

40%

80%

100%

According to one systematic review of over 300 studies, without treatment, people with ADHD had

poorer long-term outcomes in all categories compared with people without ADHD. Treatment of ADHD

(versus untreated) resulted in favorable outcomes for 72% of outcomes reported (55 of 76 outcome results

from 48 studies) (shown on left). Treatment benefits varied by outcome group (shown on right).

U.S. DEPARTMENT OF VETERANS AFFAIRS

Figure 5. ADHD pharmacotherapy reduces risk of suicidal ideation and attempts (SIA).

Incidence density rate

of SIA events per

1,000 person-years

CNS

stimulants

Non-

stimulants

No pharma-

cotherapy

According to a study in 797,189 patients with ADHD

(aged ≥ 6 years), compared with no pharmacotherapy,

central nervous system (CNS) stimulant treatment

was significantly associated with a lower risk of

SIA events in all age groups.

When subdivided by age, no significant differences were

observed between adults treated with CNS stimulants

and non-stimulants (atomoxetine, clonidine, guanfacine).

In adults, adjusted hazard ratios (HR) for SIA were as follows: 18–24 years = 0.66 (0.57–0.75, p < 0.001); 25–44 years = 0.56

(0.46–0.70, p < 0.001); ≥ 45 years = 0.74 (0.55–1.00, p < 0.05).

Before starting ADHD treatment

As with all medications, risk versus benefit ratios need consideration before initiating

any medication. Among the factors to be considered, the risks of morbidity and mortality associated

with untreated ADHD makes it important to also weigh the risk of not treating ADHD.

• The 2018 National Institute for Health and Care Excellence (NICE) ADHD Guidelines recommend

medication treatment when symptoms are still causing a significant impairment in at least one

domain of everyday life despite environmental modifications.

Before starting treatment, ensure the Veteran has an assessment that includes,

but is not limited to:

20,21,31

 Confirmation of ADHD diagnosis

 Evaluation of current medications and supplements

Review of occupational, educational, caregiving/parenting,

and relationship circumstances

Identification of coexisting physical, mental health, and

neurodevelopmental conditions

Asking women of child-bearing age about pregnancy status,

intention, and contraceptive use

A review of physical health, including baseline pulse and

blood pressure, medical history, and family medical history.

Cardiology consultation should be considered in patients with

established or suspected heart disease (e.g., significant findings

on physical exam or family history).

1,31

Assessment of care needs including risk assessment for substance misuse and drug diversion.

Vigilance identifying potential misuse or abuse of medication requires judicious follow-through

(e.g., urine drug testing [UDT] and Prescription Drug Monitoring Program [PDMP]).

Environmental modifications

Changes to the physical environment

to minimize the impact of the person’s

ADHD on day-to-day life.

Examples: changes to seating

arrangements, reducing distractions,

optimizing work to have shorter periods

of focus with movement breaks

See ADHD QRG for

more information.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Figure 6. Possible “red ags” for stimulant misuse or diversion

25,59

Symptoms of intoxication or symptoms associated with heavier use (e.g., agitation,

psychosis, shortness of breath, and palpitations)

A pattern of losing prescriptions or early re-ordering of prescriptions

PDMP check identifies unexpected medication activity; discuss finding with the Veteran

UDT contains unexpected result

–

Please note: UDT screening results for prescription stimulants should be

interpreted with caution as they are subject to false negatives and false positives.

Discuss unexpected findings with the Veteran and consider checking with your

local laboratory and/or ordering confirmation testing.

Pharmacotherapy for ADHD in adults

For most adults with ADHD, psychostimulants (amphetamines or methylphenidate) should

be considered first line.

1,31

The 2020 Canadian ADHD Practice Guidelines recommend more

specifically that longer acting psychostimulants be considered first.

Atomoxetine is generally considered as the second-line treatment for ADHD in adults.

However,

some sources recommend atomoxetine first-line when anxiety disorders, tic disorders, and/or SUD

co-occur with ADHD.

28,46,61

In general, atomoxetine should also be considered when:

1,31

• Patients experience significant side effects or have a suboptimal response with first-line medications

• Stimulant agents are contraindicated

• There is high risk of stimulant misuse

See ADHD QRG for

more information.

Table 2. ADHD medication clinical pearls

Amphetamine salts

• The most efficacious compounds, as rated by clinicians and self-report, and as well tolerated

as methylphenidate.

• More potent than methylphenidate; recommendations generally suggest a dose that is

roughly 1/2–2/3 the dose of methylphenidate.

Methylphenidate (MPH)

• Efficacy on ADHD core symptoms rated by clinicians as superior to placebo, comparable with

that of atomoxetine.

• Many products are not bioequivalent and not interchangeable on a mg/mg basis.

Atomoxetine (ATX)

• Observed effect size is generally smaller than that for psychostimulants.

• Can take several weeks for therapeutic effect, can be a barrier to adherence.

21,59

Viloxazine

• Once-daily non-stimulant recently approved for ADHD

• Similar to atomoxetine, appears to have a delayed therapeutic effect

Other medications sometimes used for ADHD in adults (e.g., bupropion, tricyclic antidepressants [TCAs], clonidine) may

have some benefit for treatment of ADHD but are generally reserved for treatment-resistant cases/specialized care.

1,65

*See QRG for more detailed information about medications.

U.S. DEPARTMENT OF VETERANS AFFAIRS

Figure 7. Stepped approach to prescribing

Set treatment

objectives

Select

medication

Provide ongoing

follow-up

Titrate and

monitor

STEP 1 STEP 2 STEP 3 STEP 4

Key points for a successful medication trial:

• Involve the patient (and their family/caregiver where clinically appropriate).

• Identify the specific ADHD symptoms that impair function to define treatment goals.

• Select treatment options and strategies to measure change.

• Start with first-line treatment options and titrate doses balancing clinical efficacy and side effects.

• Assess for use of substances (e.g., caffeine, alcohol, drugs) and provide recommendations,

support, and/or treatment as clinically appropriate.

• Measure response at planned intervals. If response is unsatisfactory, explore why and try a

different treatment option until symptom control is optimized.

• Follow up and reassess efficacy and need for treatment regularly.

Psychiatric comorbid disorders and treatment selection

Many adults with ADHD present with co-occurring disorders.

Often these need to be addressed

concomitantly; however, in some cases prioritization may need to be given to the most impairing illness

first (e.g., psychosis, severe mood disorder, bipolar disorder, active SUD [see Table 3]).

1,20,21,46

• Where mood symptoms are apparent but not pervasive, treat ADHD symptoms and monitor for

improvement first, prior to considering or initiating treatment for mood disorders.

• The presence of suicidal/violent thoughts needs to be addressed as a priority.

TAKE

NOTE

Consider a slower dose titration and provide more frequent monitoring

if any of the following are present:

• Other neurodevelopmental disorders (e.g., autism spectrum disorder, tic disorders, learning

disability/intellectual disability)

• Mental health conditions (e.g., anxiety disorders, schizophrenia or bipolar disorder, depression,

personality disorder, eating disorder, PTSD, substance misuse)

• Physical health conditions (e.g., cardiac disease, epilepsy, brain injury).

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Table 3. Co-occurring disorder considerations

Medication recommendations Treatment considerations

SUD • Atomoxetine (has efficacy in adult ADHD; little to

no abuse potential).

21,31,59

• Methylphenidate long-acting preparations

(lower abuse potential than immediate release)

• Longer-acting prodrug formulations (e.g., lisdexam-

fetamine) may have lower abuse potential than

other amphetamines.

66,67

According to the Canadian

ADHD practice guidelines, “Since the bioavailability

of the active ingredient is not influenced by route

of administration (oral, intranasal, or intravenous),

the abuse potential of this pro-drug delivery system

is significantly reduced in comparison to short-acting

medication due to the product formulation.”

• If stimulants are used, remain vigilant for any signs

of misuse or diversion (see page 18).

31,46,59,66

• Higher rate of SUD in adults with ADHD

than in the general population; ADHD

is a risk factor for SUD.

• Stimulant use in patients with SUD may

increase risk for misuse.

• Consider co-management of ADHD and SUD

with substance use disorder treatment team.

• In patients with an active, severe SUD,

SUD treatment should be the priority.

1,21,59

• If active SUD is less severe or ADHD symptoms

are severe and interfering with ability to

engage in SUD treatment, treat ADHD

and SUD concurrently

1,21,59

Generalized /

Social Anxiety

Disorder +/-

Depression

Combination of a stimulant + selective serotonin

reuptake inhibitor (SSRI) or serotonin-norepinephrine

reuptake inhibitor (SNRI).

Monitor for serotonin

syndrome.

To reduce risk of worsening anxiety, consider

starting the SSRI/SNRI first, then adding the

stimulant once anxiety symptoms have

improved, or titrate the stimulant medication

at a slower pace and monitor more frequently.

1,21

Bipolar

disorder

Stabilize the Veteran on a therapeutic dose of a mood

stabilizing medication prior to treating ADHD with a

stimulant to reduce the risk of triggering mania.

21,28

Monitor for serotonin syndrome.

• If mania is triggered, the stimulant should

be reduced or discontinued, and treatment

of bipolar disorder should be prioritized.

• Once mood is stabilized, stimulant may be

cautiously restarted (start low, go slow).

Emotional

dysregulation

• Several studies and meta-analyses have suggested

that methylphenidate has benefit for emotional

dysregulation.

27,28

• Atomoxetine may be considered after

methylphenidate as it also appears to have

some efficacy for emotional dysregulation.

27,28

• Mood stabilizers have yielded mixed results.

Treating core symptoms of ADHD with a

stimulant is often linked to a beneficial effect

on emotional dysregulation and should be

considered the first line of treatment.

DEPRESSION

SUD

BIPOLAR

U.S. DEPARTMENT OF VETERANS AFFAIRS

Pregnancy considerations

Decisions about stimulants for ADHD in pregnancy are especially challenging.

There is a paucity of high-quality studies of stimulants in pregnancy and the risks of

untreated ADHD vary. That said, stimulants are not among the highest-risk medications

during pregnancy. In many cases, the risks of untreated ADHD are substantial and

exceed the risks of stimulants, especially amphetamine/dextroamphetamine.

69-71

When clinically indicated, a detailed history and pregnancy test can be used to

assess the intention of becoming pregnant and current pregnancy status of a

woman of child-bearing potential.

• Having this conversation ahead of time allows for the development of a treatment

plan compatible with pregnancy for anyone who might become pregnant, and to

include perinatal consideration in the risk/benefit discussion.

• These discussions are important even for medications with favorable perinatal safety profiles.

Without such discussions, a patient may abruptly discontinue a medication on learning of a

pregnancy, even if the risks of the untreated symptoms outweigh the risks of the medication.

DID

YOU

KNOW

The VA Reproductive Mental Health Consultation Program

is available to help clinicians: ReproMHC[email protected].

Non-pharmacologic treatment

11,20,21,24,31,44,46,47,49

When treating adults with ADHD, it is imperative to address not only core symptoms of ADHD

but also the affected sleep behaviors, perceived stress, and maladaptive coping styles to maximize

the potential for overall increases in well-being.

47,72

Various non-pharmacologic interventions such as cognitive behavioral therapy,

cognitive remediation and rehabilitation, and mindfulness-based therapies

have shown efficacy for ADHD core behavioral symptoms and/or associated

dysfunction and are generally well tolerated.

Benefits of psychosocial

treatments are more apparent for executive functioning and functional

impairment, rather than on ADHD symptom checklists.

24,47

• Other psychotherapeutic principles and techniques can be useful under specific circumstances

(e.g., couples therapy can be used to increase communication skills and conflict resolution).

• Consider referral to Occupational Therapy for daily life management skills (e.g., paying bills on time;

using electronic devices for reminders; improved efficiency at home, work, or school).

For adults with ADHD with prominent deficits in executive functioning, consider combined treatment

(pharmacotherapy + non-pharmacologic treatment).

21,48

Provide evidence-based treatment to Veterans with ADHD.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Monitoring, follow-up, and continued care

Assessing treatment response

In general, stimulant effects are likely to be stable

at a given dose after 1-3 weeks (for atomoxetine,

after 4-6 weeks).

A 6-week trial at an optimal,

tolerated dose is recommended before switching

to or adding on another ADHD treatment.

Use subjective impressions of response along with

objective measures to guide dosage adjustments,

treatment switch, or add-on therapy.

While treatment success could be defined as remission of all ADHD symptoms, improvement should

be clinically significant and represent observable change from baseline.

DID

YOU

KNOW

An excessive dose of a

stimulant medication can

induce an inflexible pattern

of responding (e.g., as

would be seen following

uncontrollable stress),

restricted affect, and/or

cognitive inflexibility.

1,18

See QRG

See ADHD QRG for more information on use of rating scales to measure change.

ADHD symptom control

• Use validated rating scales to monitor response and assess changes in ADHD symptoms.

21,56

This increases positive clinical outcomes and chance of remission.

21,56

Changes in functioning/quality of life

• Assess functional benefits from symptom control at each visit (e.g., functional impairment,

quality of life, executive function).

–

Consider getting input from other sources (e.g., family members, coworkers) to assess

impact of ADHD treatment.

21,56

Tolerability of medication

• Ask the Veteran about the positive and negative effects of the medication and duration

of these effects at each visit and following each dose adjustment.

• Ask about adverse effects in a “review of systems” manner focusing on the most likely

adverse effects of each medication.

See ADHD QRG for common adverse effect

information.

U.S. DEPARTMENT OF VETERANS AFFAIRS

An excessive dose of a

stimulant medication can

induce an inflexible pattern

of responding (e.g., as

would be seen following

uncontrollable stress),

restricted affect, and/or

cognitive inflexibility.

1,18

Table 4. Monitoring and follow-up considerations

Robust

response

Continue medication. Note: timing of the stimulant dose(s) may still

need to be adjusted despite overall robust response.

Partial

response

21,31

• Consider dose adjustment to account for total versus peak dose effects (e.g.,

the Veteran may need an additional dose later in the day instead of morning)

• Consider increasing to the maximum recommended therapeutic dose.

• Consider augmentation with non-pharmacologic treatment for Veterans

who are tolerating the medication but only having a partial response.

• Consider switching medications. No washout or tapering is necessary

in switching from one stimulant medication to another.

Unable to

tolerate

1,21,31

Consider a different medication or formulation if the Veteran is unable to

tolerate a therapeutic dose.

• When adverse effects are not mild or pose risk, consider changing to a

different class of medication or managing an underlying vulnerability.

• When adverse effects are mild or seem related to the delivery system, consider

a product with a different pattern of release of the same active ingredient.

Please note: If negative symptoms are experienced at the time when medications would be expected to be wearing off,

or with sudden cessation of pharmacotherapy, the symptoms may be from the medication wearing off too quickly.

If the initial stimulant fails to deliver an optimal response, evidence supports the

need for sequential trials of both stimulants (amphetamines, methylphenidate) before

deeming stimulants unsuccessful.

For Veterans with partial or no response to treatment, review both the diagnosis

(including comorbidities) and treatment plan to ensure compliance to treatment as

well as to check if there are external factors that could complicate the clinical picture.

Consider obtaining a second opinion or referring to a mental health provider if ADHD

symptoms are unresponsive to one or more stimulants and one non-stimulant.

Maintenance treatment

Long-term benefit of ADHD treatment is a controversial area

and recommendations typically suggest to individualize

treatment plans and consider risks versus benefits of

long-term treatment.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

Monitoring recommendations

After stabilization of symptoms, reassess treatment response and adherence, vital signs, and side

effects/adverse effects at least once a year.

ADHD patients can benefit from having access to

mental health care when needed during their life-course with ADHD.

onitor Veterans on stimulants + SSRI/SNRI/tricyclic antidepressants (TCA)

for serotonin syndrome. Other medications and over-the-counter agents can

also precipitate serotonin syndrome when combined with stimulants (e.g., MAO-Is,

lithium, linezolid, triptans, St John’s Wort, etc.); refer to medication package insert

for more about drug interactions.

Measure heart rate and blood pressure regularly during treatment.

21,31,73

• To assess the effects of medications on vital signs, it may be useful to take measures

before a dose is taken and compare to measures while the dose is active.

• If a person taking ADHD medication has sustained resting tachycardia ( > 120 beats

per minute), arrhythmia or significant increase in blood pressure measured on two

occasions, consider reducing the dose by half and refer for assessment. Ask about

caffeine use and recommend to reduce or avoid use as needed.

onitor for the appearance of, or worsening of, aggressive or anxious

behavior and sleep disturbances.

Remain vigilant and assess risk for substance misuse and drug diversion

(e.g., PDMP checks, UDT as clinically appropriate).

Consider monitoring body mass index (BMI) in adults with ADHD if there has

been weight change as a result of their treatment, and changing the medication

if weight change persists.

Continue to assess, support, and oversee treatment of mental health care needs.

Treatment considerations for older adults

As patients with ADHD age, several factors may impact the risk versus benefit assessment:

75,76

• Possible reduction or remission of ADHD symptoms, particularly hyperactivity

20,24,26

• Age-related decline of liver and kidney function may impact drug metabolism

• Increased number of comorbidities (e.g., cardiovascular disease, glaucoma)

• Increased number of medications and subsequently the risk

of drug-drug interactions

• Greater risks from side effects (e.g., appetite reduction, insomnia, dry mouth, tremors)

U.S. DEPARTMENT OF VETERANS AFFAIRS

What you can do:

Understand how ADHD symptoms have affected the Veteran’s health, quality of life, and

function when weighing the benefits versus risks of continuing pharmacotherapy.

Assess for use of drugs, alcohol, and other substances (e.g., caffeine) and encourage the

Veteran to minimize use. Offer evidence-based treatment when clinically applicable.

Individualize treatment plans to minimize risk and maximize benefits. Consider:

–

Adjusting the dose, formulation, or switching to a different medication to minimize risks

–

Tapering and discontinuing the medication if risks outweigh benefits

–

Using non-pharmacologic treatments either alone or in addition to pharmacotherapy

Follow up with Veterans after treatment plan changes to ensure benefits are outweighing

the risks and provide follow-up care as needed.

Supporting people with ADHD

Studies highlight the need for long-term psychiatric and psychosocial support in patients with ADHD,

regardless of pharmacologic or non-pharmacologic treatment.

Patients diagnosed with ADHD will

often go through a three-step process:

Immediate relief Frustration Self-acceptance

The initial sense of relief stems from validation of the experience, and its

sequelae, and optimism for treatment.

Frustration often ensues as patients realize they have a chronic condition

and recall their past experiences and life decisions that may have been different

if the condition was recognized and treated sooner.

Self-acceptance occurs when a patient embraces ADHD as a life-long condition

that is not singularly defining yet may help explain prior self-defeating behavior

and decision-making.

Identication and Management of Attention-Decit/Hyperactivity Disorder (ADHD) in Adults

References

1. 4.1 Edition Canadian ADHD Resource Alliance: Canadian ADHD Practice Guidelines (CADDRA) (2020).

2. Humphreys KL, et al. JAMA Psychiatry. 2013;70(7):740-9.

3. Molina BS, et al. J Am Acad Child Adolesc Psychiatry. 2013;52(3):250-63.

4. Wilens TE, et al. Arch Pediatr Adolesc Med. 2008;162(10):916-21.

5. Wilens TE, et al. Pediatrics. 2003;111(1):179-85.

6. National Institute on Drug Abuse. Overdose Death Rates. National Institutes of Health. Accessed April 16, 2022,

https://nida.nih.gov/drug-topics/trends-statistics/overdose-death-rates

7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision.

American Psychiatric Publishing; 2022.

8. Faraone S, et al. World Psychiatry. 2003;2(2):104-13.

9. Wolraich ML, et al. Pediatrics. 2019;144(4):e20191682.

10. Sibley M. J Clin Exp Neuropsychol. 2021;43(4):340-351.

11. Geffen J, Forster K. Ther Adv Psychopharmacol. 2018;8(1):25-32.

12. Kessler RC, et al. JAMA Psychiatry. 2014;71(5):504-513.

13. Childress AC, et al. Expert Opin Drug Metab Toxicol. 2019;15(11):937-974.

14. Fayyad J, et al. Atten Defic Hyperact Disord. 2017;9(1):47-65.

15. Kok BC, et al. J Atten Disord. 2019;23(9):968-975.

16. Sibley MH, et al. Am J Psychiatry. 2022;179(2):142-151.

17. Kessler RC, et al. Am J Psychiatry. 2006;163(4):716–723.

18. Arnsten AF. J Pediatr. 2009;154(5):I-S43.

19. Bjerrum MB, et al. JBI Database System Rev Implement Rep. 2017;15(4):1080-1153.

20. Bukstein O. Attention deficit hyperactivity disorder in adults: epidemiology, pathogenesis, clinical features, course,

assessment, and diagnosis. Wolters Kluwer. Updated October 8, 2021. Accessed March 29, 2022, https://www.up-

todate.com/contents/attention-deficit-hyperactivity-disorder-in-adults-epidemiology-pathogenesis-clinical-fea-

tures-course-assessment-and-diagnosis

21. Brent D, et al. Treatment of Attention Deficit Hyperactivity Disorder in Adults. Wolters Kluwer. Updated October 18,

2021. Accessed March 29, 2021, https://www.uptodate.com/contents/treatment-of-attention-deficit-hyperactivity-

disorder-in-adults

22. Oliva F, et al. Early Interv Psychiatry. 2021;15:957-965.

23. Butzbach M, et al. J Clin Exp Neuropsychol. 2021;43(4):384-98.

24. Lücke C, et al. Int J Ment Health. 2021;50(3):250-270.

25. McCoy KT, et al. Nurs Clin North Am. 2019;54(4):517-532.

26. Biederman J, et al. Am J Psychiatry. 2000;157(5):816-8.

27. Shaw P, et al. Am J Psychiatry. 2014;171(3):276-293.

28. Perugi G, et al. Expert Opin Pharmacother. 2019;20(12):1457-1470.

29. Young S, et al. BMC Psychiatry. 2020;20(1):404.

30. Dalsgaard S, et al. Lancet. 2015;385(9983):2190-6.

31. National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: Diagnosis and management.

Accessed December 22, 2020, https://www.nice.org.uk/guidance/ng87

32. Ginsberg Y, et al. Prim Care Companion CNS Disord. 2014;16(3):PCC.13r01600.

33. Rucklidge JJ. Psychiatr Clin North Am. 2010;33(2):357-373.

34. Kakuszi B, et al. Compr Psychiatry. 2018;85:23-29.

35. Moffitt TE, et al. Am J Psychiatry. 2015;172(10):967-77.

36. Klein RG, et al. Arch Gen Psychiatry. 2012;69(12):1295-303.

37. Biederman J, et al. J Clin Psychiatry. 2012;73(7):941-950.

U.S. DEPARTMENT OF VETERANS AFFAIRS

38. Barkley RA, Fischer M. J Atten Disord. 2019;23(9):907-923.

39. Fitzgerald C, et al. Br J Psychiatry. 2019;1-6.

40. Cipollone G, et al. J Clin Med. 2020;9(11):3788.

41. Ustun B, et al. The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening

Scale for DSM-5. JAMA Psychiatry. 2017;74(5):520-527.

42. Lovett BJ, Harrison AG. J Clin Exp Neuropsychol. 2021;43(4):333-339.

43. Brod M, et al. Primary Psychiatry. 2005;12(6):58-64.

44. Asherson P, et al. Lancet Psychiatry. 2016;3(6):568-78.

45. Shura RD, et al. Military Psychology. 2016;29(1)(1):27-40.

46. Hackett A, et al. JAAPA. 2020;33(8):12-16.

47. Solanto M. Psychotherapy for attention deficit hyperactivity disorder (ADHD) in adults. Wolters Kluwer. Updated

October 18, 2021. Accessed March 29, 2021, https://www.uptodate.com/contents/psychotherapy-for-attention-

deficit-hyperactivity-disorder-adhd-in-adults

48. Fullen T, et al. J Psychopathol Behav Assess. 2020;42(3):500-18.

49. Philipsen A, et al. JAMA Psychiatry. 2015;72(12):1199-210.

50. Nimmo-Smith V, et al. Psychol Med. 2020;50(4):529-541.

51. Knouse LE, et al. J Consult Clin Psychol. 2017;85(7):737-750.

52. Harpin V, et al. J Atten Disord. 2016;20(4):295-305.

53. Lichtenstein P, et al. N Engl J Med. 2012;367(21):2006-14.

54. Chang Z, et al. JAMA Psychiatry. 2017;74(6):597-603.

55. Shaw M, et al. BMC Med. 2012;10:99.

56. Caye A, et al. Molecular Psychiatry. 2019;24:390-408.

57. Siffel C, et al. J Affect Disord. 2020;266:109-119.

58. Berger S. Cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder.

Wolters Kluwer. Accessed March 29, 2021, https://www.uptodate.com/contents/cardiac-evaluation-of-patients-

receiving-pharmacotherapy-for-attention-deficit-hyperactivity-disorder

59. Johnson J, et al. Addictive Disorders & Their Treatment. 2021;20(3):181-188.

60. Faraone SV, Glatt SJ. J Clin Psychiatry. 2010;71(6):754-763.

61. Adler LA, et al. Depress Anxiety. 2009;26(3):212-221.

62. Cortese S, et al. Lancet Psychiatry. 2018;5(9):727-738.

63. Steingard R, et al. J Child Adolesc Psychopharmacol. 2019;29(5):324-339.

64. Methylphenidate. Lexi-Drugs. Hudson, OH: Lexicomp, 2022. http://online.lexi.com. Accessed May 2, 2022.

65. Verbeeck W, et al. Cochrane Database Syst Rev. 2017;10(10):Cd009504.

66. Goodman DW. Pharmacy and Therapeutics. 2010;35(5):273-287.

67. Weber J, Siddiqui MA. CNS Drugs. 2009;23(5):419-25.

68. Mariani JJ, Levin FR. Am J Addict. 2007;16 Suppl 1(Suppl 1):45-54; quiz 55-6.

69. Huybrechts KF, et al. JAMA Psychiatry. 2018;75(2):167-175.

70. Kolding L, et al. J Clin Psychiatry. 2021;82(1):20m13458.

71. Bro SP, et al. Clin Epidemiol. 2015;7:139-47.

72. Jain R, et al. Prim Care Companion CNS Disord. 2017;19(5):17nr02153.

73. Wilens TE, et al. J Clin Psychiatry. 2005;66(2):253-9.

74. Post RE, Kurlansik SL. Am Fam Physician. 2012;85(9):890-6.

75. Goodman DW, et al. Drugs Aging. 2016;33(1):27-36.

76. Torgersen T, et al. Neuropsychiatr Dis Treat. 2016;12:79-87.

Acknowledgments

THIS GUIDE WAS WRITTEN BY:

Daina L. Wells, PharmD, MBA, BCPS, BCPP

Sarah J. Popish, PharmD, BCPP

Julianne E. Himstreet, PharmD

WE THANK OUR EXPERT REVIEWERS:

Matthew J. Barry, DO

Bruce Capehart, MD

Matthew A. Fuller, PharmD, FASHP, BCPP

Andrea Goldenson, PharmD, PhD

Eric Hermes, MD

Laura J. Miller, MD

Melisa Perednik, PharmD, BCPP

Jennifer L. Powers, PharmD, BCPS

Jennifer R. Purdy

Matthew Schreiber, MD, PhD

Antoinette V. Shappell, MD

Robert D. Shura, PsyD, ABPP-CN

This reference guide was created to be used as a tool for VA providers and is available

from the Academic Detailing SharePoint.

These are general recommendations only; specific clinical decisions should be made

by the treating provider based on an individual patient’s clinical condition.

VA PBM Academic Detailing Services Email Group:

PharmacyAcademicDetailingProgr[email protected]

VA PBM Academic Detailing Services SharePoint Site:

https://dvagov.sharepoint.com/sites/vhaacademicdetailing

VA PBM Academic Detailing Services Public Website:

http://www.pbm.va.gov/PBM/academicdetailingservicehome.asp

July 2022 IB 10-1520 P97040