Drugs Aging

DOI 10.1007/s40266-015-0327-0

REVIEW ARTICLE

Clinical Presentation, Diagnosis and Treatment of Attention-

Deficit Hyperactivity Disorder (ADHD) in Older Adults: A Review
of the Evidence and its Implications for Clinical Care
David W. Goodman1,2,3 • Sara Mitchell4 • Lauren Rhodewalt5 • Craig B. H. Surman5,6

Ó Springer International Publishing Switzerland 2015

Abstract Although previously considered a disorder of been systematically explored. In light of the limited data,
childhood, studies in the last decade have demonstrated this review discusses considerations for differential diag-
that attention-deficit hyperactivity disorder (ADHD) con- nosis and safe pharmacotherapy of ADHD in older adults.
tinues to impair function into adulthood and responds to
pharmacotherapy. Due to age-specific changes in roles and
challenges, it is possible that presentation and response to
Key Points
intervention may differ between older and younger adults.
A literature search for papers that identified older adults
Attention-deficit hyperactivity disorder (ADHD) is a
with ADHD, including papers describing its epidemiology,
chronic neuropsychiatric disorder that may impact
manifestation, and treatment, was the basis for this paper.
3 % of older adults.
There is a paucity of data on ADHD in older adults;
however, small observational studies have characterized While diagnostic assessment of adult ADHD has
the presence, impact, and treatment of ADHD in adults been recently refined, the symptom definitions may
over the age of 50 years, and larger epidemiologic studies need to be modified for use in older adults.
have demonstrated that ADHD symptoms exist in older Diagnosis in older adults requires identification of
adulthood. Optimal criteria for diagnosis of ADHD and past and current symptoms, and differential
methods of treating ADHD in older individuals have not diagnosis should include other neuropsychiatric
conditions.

& David W. Goodman

Trials should be conducted in older adults to
dgoodma4@jhmi.edu determine best treatment approaches (medication
and psychotherapies).
1
Department of Psychiatry and Behavioral Sciences, Johns
Hopkins School of Medicine, Baltimore, USA
2
Adult Attention Deficit Disorder Center of Maryland,
Lutherville, USA
3
1 Introduction
Suburban Psychiatric Associates, LLC Johns Hopkins at
Green Spring Stations, 10751 Falls Rd, Suite 306, Baltimore,
MD 21093, USA It is expected the population of persons older than 65 years
4 of age in the US will grow from 43.1 million to
Department of Neurology, Massachusetts General Hospital,
15 Parkman Street, WAC 815, Boston, MA 02114, USA 88.5 million between 2012 and 2050 [1]. Attention-deficit
5 hyperactivity disorder (ADHD) will be one of many psy-
Clinical and Research Program in ADHD and Related
Disorders, Massachusetts General Hospital, 55 Fruit Street, chiatric contributors to morbidity in this aging population.
Warren 631, Boston, MA 02114, USA In the last decade, the validity of ADHD in adults and its
6
Harvard Medical School, 25 Shattuck St, Boston, MA 02115, continued impact in adulthood has been well demonstrated
USA through genetic studies [2] and long-term follow-up of
 D. W. Goodman et al.

children into adulthood [3]; however, these studies have ADHD in the National Comorbidity Study–Replication
not included adults beyond the fourth decade of life. For (NCS–R) were not diagnosed as children [12]. In addition,
example, reports from seven prospective longitudinal current diagnostic criteria for ADHD, emphasizing the
studies include follow-up of up to 33 years [3], where the impact of inattention symptoms and not just hyperactive-
oldest reported subject was 41 years of age. It is common impulsive symptoms, trace back to revisions in the DSM in
to exclude individuals over the age of 65 years from clin- 1980. This means that clinicians will often be assessing
ical trials of ADHD pharmacotherapy, out of concern of individuals who have never been assessed previously.
misinclusion of individuals with non-ADHD cognitive Pharmacotherapy for ADHD with catecholaminergic
disorders. The literature has described the impact of ADHD agents such as psychostimulants has been shown to be
in adult roles such as workplace performance and family effective in multiple clinical trials in children and adults,
life [4], but with age it is possible that ADHD will manifest and some studies have demonstrated both symptom and
differently as changes in roles or life circumstances occur. functional improvement [13]. Maturation of the central
Some prevalence studies have employed ADHD diag- nervous system, onset of new brain or systemic medical
nostic criteria to explore the rate of ADHD in adults conditions, and other medications could impact the efficacy
beyond the fifth decade of life; however, there has been and tolerability of ADHD pharmacotherapies. Because of
little epidemiologic study of ADHD in this age group. The these age-specific concerns, we sought to determine clini-
National Epidemiologic Survey on Alcohol and Related cally relevant evidence for identification and treatment of
Conditions (NESARC) DSM-IV interviews conducted in ADHD in older adults. Specifically, we sought evidence of
the US in 2004–2005 estimated that 2.51 % of a sample of the clinical presentation, validity of assessment methods,
34,653 adults had ADHD, where 35 % were over the age of and efficacy of therapies.
45 years [5]. The Longitudinal Aging Study Amsterdam We conducted a literature search for English-language
(LASA) estimated a prevalence rate of 2.8 % among adults publications in the National Library of Medicine PubMed
aged 55–85 years using a semi-structured interview fol- database using the search term ‘ADHD in older adults’,
lowing the DSM-IV-TR diagnostic criteria [6]. A German without a date restriction. This was supplemented with
study used childhood and adulthood symptom screeners to articles referenced in papers identified by this search, and
estimate the prevalence of ADHD in 1655 adults aged articles known to be relevant to the authors. We restricted
18–64 years, finding that among the 396 adults who were report collection to articles that specifically described
55–64 years of age, 3.5 % were likely to have ADHD [7]. results for individuals over the age of 50 years. Evidence
In a population-based Swedish survey, 3.3 % of 2500 relevant to the presentation, assessment, and treatment of
adults aged 65–80 years had evidence of childhood ADHD ADHD in older adults was gathered.
(from responses on the Wender Utah Rating Scale Studies to date on ADHD in older adults offer initial
[WURS]), although this study did not confirm the presence evidence of how ADHD manifests in this population group,
of a current diagnosis [8]. These rates are lower than a how it can be differentiated from other conditions, and
4.4 % estimate of ADHD in adulthood from a US study of considerations in the treatment of ADHD. These issues are
individuals aged 18–44 years utilizing direct interviews discussed in the following sections.
[9]. A meta-analysis of ADHD prevalence in studies uti-
lizing different age ranges spanning 18–74 years suggests
that, within adulthood, prevalence may decline with age 2 Clinical Presentation of Attention-Deficit
[10]. Hyperactivity Disorder (ADHD) in Older
No neuropsychological test is available to diagnose Adulthood
ADHD, and no test is required in the criteria of the DSM-V
(see Table 1 for ADHD criteria [9, 11]). Clinicians only By definition, ADHD requires impairment in functioning
have the report of the patient and/or third parties, such as due to ADHD traits. Impact on academic, occupational,
family report and medical or school records, to determine if and social function is well documented in younger adults,
the diagnostic criteria are fulfilled. but hallmarks of functional impairment in older adults can
Diagnostic considerations during initial evaluation for be presumed to have different patterns in the years beyond
ADHD should be age-appropriate. The differential diag- school and work roles. We identified only four studies that
nosis for cognitive impairments expands to include normal described cases currently meeting all the criteria for ADHD
aging, medications, medical illness, or onset of cognitive beyond the age of 50 years. These included a case report of
disorders. Many older adults with ADHD were not diag- a 68-year-old woman with DSM-IV ADHD [14], nine
nosed as children, in part because ADHD was poorly rec- women between the ages of 62 and 91 years diagnosed
ognized decades ago. This idea is supported by the finding with ‘ADHD’ in Texas and participating in group therapy
that 75 % of adults aged between 18 and 44 years with [15], a chart review in Israel of 11 individuals with DSM-
ADHD in Older Adults: A Review of Evidence and Implications for Care

Table 1 Symptoms of ADHD (as adapted from the World Health Organization adult ASRS) and the diagnostic criteria (as adapted from the
DSM-V) [9, 11]
Symptoms of ADHD
Inattentive presentation symptoms:
Often fails to wrap up the final details of a project once the challenging parts have been done
Often has trouble getting things in order when performing a task that requires organization
Often has problems remembering appointments or obligations
Often avoids or delays getting started on tasks that require a lot of thought
Often makes careless mistakes when working on a boring or difficult project
Often has difficulty paying attention when doing boring or repetitive work
Often has difficulty concentrating on what is being said, even when spoken to directly
Often misplaces or has difficulty finding things at home or at work
Often distracted by activity or noises
Hyperactive/impulsive presentation symptoms:
Often fidget or squirm with their hands or feet when they have to sit for a long period of time
Often feels overly active and compelled to do things, like they are driven by a motor
Often leave their seat in meetings or other situations in which they are expected to remain seated
Often feels restless or fidgety
Often has difficulty unwinding and relaxing when they have time to themselves
Often talk too much when in social situations
Often finishes the sentences of the people they are talking to before they can finish themselves
Often has difficulty waiting for their turn in situations when turn-taking is required
Often interrupts others when they are busy
Adult ADHD diagnostic criteria
5? current inattentive or 5? impulsive/hyperactive symptoms for 6 months to an extent that is disruptive and inappropriate
Symptoms present prior to the age of 12 years
Symptoms interfere with functioning and are present in two or more settings or roles
Symptoms not explained by another disorder
Diagnosis can be made of predominantly inattentive, predominantly hyperactive/impulsive, or combined presentations based on the pattern
of symptoms
ADHD attention-deficit hyperactivity disorder, ASRS ADHD Self-Report Scale, DSM-V Diagnostic and Statistical Manual of Mental Disorders,
5th edition

IV-TR ADHD [16], and 60 individuals over the age of number of ADHD symptoms was positively correlated with
65 years selected from a Swedish population study [8]. the presence of chronic, nonspecific lung diseases
Each of these reports documented the presence of impaired (B = 2.58, p = 0.02), cardiovascular diseases (B = 2.18,
functioning related to ADHD traits. In the Israeli sample, p = 0.02), and the number of chronic diseases (B = 0.69,
impairment was characterized as mild in 27 % of subjects, p = 0.04), and negatively associated with self-perceived
moderate in 45 %, and severe in 27 % [16]. health (B = -2.83, p = 0.002); however, there was no
In a subset of over 200 individuals in the LASA study, association between substance use, exercise, or other life-
criteria were less strictly applied by interview, lacking style variables and symptoms of ADHD [19].
sufficient description to answer the question of whether Further evidence for ADHD morbidity later in life
symptoms should be attributed to ADHD and not another comes from studies that characterized the presentation of
condition. In this subset of the Amsterdam study, in indi- individuals who self-reported an ADHD diagnosis. In a US
viduals age 60–94 years, ADHD diagnosis correlated with phone interview of 24 older adults aged 60–77 years, none
being divorced or never married, and emotional or social were diagnosed as children and the mean age at diagnosis
loneliness [17]. The presence of ADHD was significantly was 57 years; 63 % had comorbid psychiatric conditions.
negatively correlated with self-reports of traits of mastery, When asked about the burden of ADHD, 63 % reported a
self-esteem, and self-efficacy, and positively associated financial impact and 71 % reported a social impact. On the
with neuroticism and social inadequacy. A sense of mas- Adult ADHD Quality of Life measure (AAQoL), these
tery and self-esteem were mediators in the relationship adults reported lower life productivity but better life out-
between ADHD and depressive symptoms [18]. The look in comparison with a normative sample of younger
 D. W. Goodman et al.

adults with ADHD. Some participants mentioned that adults. Applying the cut-off of DSM symptom item fre-
understanding the disorder and living with the symptoms quency thought to correlate with ADHD in younger adults
got easier with age [20]. [12], 4 % fewer older adults (68–74 years) than middle-age
A Norwegian sample of 148 adults aged 50–69 years adults (48–52 years) screened positive for ADHD in a
with a self-reported diagnosis of ADHD completed the sample of 3443 adults [12]. The idea that ADHD symptom
EuroQol and the Satisfaction With Life Scale, reporting burden may be lower in older adults is consistent with
significantly worse health-related quality of life and satis- findings in a survey of 720 individuals aged 18–84 years
faction compared with age-matched populations. Non- who were screened for ADHD symptoms when presenting
employment and severe ADHD symptoms were associated for driving-license renewal [24]. DSM-V uses a lower
with poor quality of life [21]. Further evidence for a con- number of symptoms in the criteria for individuals over
nection between ADHD and poorer life outcomes comes versus under age 17 years, but further study is necessary to
from a Swedish population survey study, which demon- demonstrate if required symptom burden should be further
strated that, numerically, a larger percentage of individuals adjusted in older adults.
who reported childhood ADHD symptoms were likely to Preliminary studies have explored the utility of Wender
be unmarried or divorced, have less biological offspring, childhood and adult ADHD scales in older adults. It is
had more jobs over their lives, and have higher WURS notable that these scales include DSM ADHD traits as well
scores (over 36) in these later years of age [8]. as associated behavioral or emotional symptoms that are
Initial studies, which used varying levels of diagnostic not included in current DSM criteria. In a Swedish popu-
confirmation of ADHD, suggest that ADHD is associated lation-based sample, high levels of childhood symptom
with lower quality of and satisfaction with life late into inventory on a version of the WURS scale correlated, but
adulthood. It should be expected that the self-regulation did not fully predict, symptoms on a Swedish version of the
challenges of ADHD will manifest uniquely in each indi- Wender–Reimherr Adult Attention Deficit Disorder Scale
vidual, and will depend on external circumstances such as (WRAADDS) [25]. The same group found correlation
the level of compensation for these challenges afforded by between the WURS childhood and WRAADDS adult
supportive relationships. Occurrence of ADHD in a family symptom scales and corresponding Barkley scales. The
member suggests a higher likelihood of an ADHD diag- performance of these scales also correlated with DSM-IV
nosis. However, neuropsychological testing can be helpful childhood and adult symptoms reported on interview [25].
in measuring the severity of attention problems relative to However, it would take more systematic study of scale
other cognitive impairments, and evaluating decline in performance to determine their correlation with clinical
deterioration in cognitive functioning, which may mimic diagnosis in older adults.
ADHD. To our knowledge, there is only one study that informs
the question of whether the factor structure of ADHD pre-
sentations applies to older adults. This study found similar
3 How Should ADHD Symptoms Be Identified evidence for hyperactive, inattentive, and combined mani-
in Older Adults? festations of typical DSM ADHD symptoms between
younger and older individuals in a sample aged 18–75 years
While there are several validated scales for adult ADHD, we [26].
only found evidence of three studies that explored symptom
assessment in geriatric patients. A substudy of LASA [19]
applied an ADHD screener (consisting of DSM ADHD 4 Differential Diagnosis of ADHD in Older Adults
symptoms and executive function symptoms associated with
ADHD in younger adults [22]) to 1494 adults age The few studies characterizing the clinical presentation of
60–94 years, then identified if ADHD was present using a older adults with ADHD noted prevalent mental health
structured interview in 231 of these adults. While the screener comorbidity. All nine of the women in the Texas report had
performed with reasonable sensitivity (0.80) and specificity depression, two had bipolar disorder, and seven had anxiety
(0.77), the test–retest validity was moderate at 0.56. The low disorders [15]. Six of the 11 Israeli cases reported Axis I or
test–retest validity suggests it could be important in devel- II comorbidity [16].
oping a screener specifically for older adults. Analysis of the LASA subset study of adults aged
The Australian Personality and Total Health (PATH) 60–94 years (described previously) found that the associ-
Through Life study [23] utilized the World Health Orga- ation of ADHD with anxiety and depression was
nization ADHD Self-Report Scale (ASRS) screener for stable over three assessments in a 6-year time span. A
ADHD, and also suggests that symptoms used to identify higher level of ADHD symptoms was independently rela-
ADHD in younger adults may manifest differently in older ted to an increase of depressive symptoms [27].
ADHD in Older Adults: A Review of Evidence and Implications for Care

It is clear that ADHD often presents comorbidly with visuospatial dysfunction with potential accompanying
other current or lifetime Axis I DSM conditions, con- apraxia, agnosia, or aphasia is suggestive of Alzheimer’s
founding identification [28, 29]. For example, 47 % of disease; personality change and apathy is suggestive of
adults aged 18–44 years who screened positive for ADHD behavioral variant frontotemporal dementia [33], while
in the NCS-R study had a coexisting anxiety disorder (the stepwise decline in cognitive function is suggestive of
most common being social anxiety) and 38 % had a vascular dementia [34]. Progressive gait disturbance or
coexisting mood disorder. Overall, the rate of comorbid other parkinsonian features may indicate the presence of a
psychiatric disorders was three to seven times that of the parkinsonian syndrome [35].
general population [12]. Similarly, data from the NESARC Rapid cognitive decline over weeks and months, with
study suggest that, in adults 18 years of age and over, motor abnormalities should lead to an expedited work-up
ADHD was significantly associated with an increased risk for prion or other rapidly progressive dementias [36].
for bipolar disorder, generalized anxiety disorder, post- Acute onset, fluctuations in cognition or level of alertness,
traumatic stress disorder, and specific phobia and person- or systemic illness should lead to a full investigation of
ality disorders (narcissistic, histrionic, borderline, antiso- potential toxic/metabolic syndromes and inflammatory/in-
cial, and schizotypal) independent of the effects of fectious etiologies. Post-concussive syndrome or chronic
comorbid psychiatric disorders [5]. traumatic encephalopathy may present with primary alter-
It has been suggested that, when possible, other Axis I ation in attention but, unlike ADHD, may have accompa-
conditions should be treated to eliminate the possibility of nying headaches, vertigo, photophobia and/or
pseudo-ADHD before attempting to confirm and treat parkinsonism [37, 38]. The presence of space occupying
ADHD. When a patient with ADHD presents with a lesions or multiple sclerosis should be considered if there
comorbid mental health condition, it is prudent to address are other focal neurological symptoms such as headaches,
the most severe problems for which evidence-based treat- focal limb numbness/weakness, and/or visual complaints.
ment can be offered. Clinicians may choose, for example, Episodic loss of attention should trigger investigation to
to treat severe alcohol/substance use disorders first, severe rule out epileptiform activity in the brain. Finally, a thor-
and acute mood disorders next, followed by severe anxiety ough sleep history, including a history of snoring and
disorders, and finally ADHD [30]. No research is available apneic episodes, should be obtained to screen for obstruc-
to guide the order in which conditions should be treated, tive sleep apnea and other sleep disorders that may be
therefore clinicians should monitor the impact on each reversible causes of daytime impairment [39–41].
domain of concern as they treat. Special care should be One survey suggests that ADHD is not being identified
given to identify mental health conditions that might be often in later-life cognitive presentations. Of 62 memory
exacerbated by ADHD pharmacotherapy, including any disorder clinics, only one in five reported regularly
history of agitated states such as psychosis and mania, or screening for ADHD, although 60 % reported seeing
substance use history that may suggest risk of misuse or ADHD patients [42].
abuse of pharmacotherapy. It has been suggested that ADHD could predispose to
higher rates of other cognitive disorders but there is
4.1 Differentiating ADHD from Other Disorders inadequate research to substantiate this connection. To
our knowledge, only two studies have preliminarily
Normal aging, mild cognitive impairment, dementia, and a explored the association of ADHD with cognitive disor-
variety of systemic conditions can manifest with behavior, ders. Both studies used the WURS to estimate the pres-
attention, executive function and memory challenges that ence of childhood ADHD symptoms. An Argentinian
overlap with those of ADHD. Mild cognitive impairment study found significantly higher rates of suspected
may occur in 16 % of the geriatric population [31]. This childhood ADHD in 109 individuals with clinical diag-
concern is reflected in the methodology of the LASA and noses of Lewy Body Dementia than in 251 individuals
PATH studies, which excluded individuals based on Mini- with Alzheimer’s dementia or 149 control subjects.
Mental Status Examination scores. However, the control group had a high rate (15 %) of
Table 2 summarizes common differentiating aspects of childhood ADHD on the WURS, raising questions about
presentation and work-up. The presence of lifelong symp- the conclusions that can be drawn from the methodology
toms differentiates ADHD from many conditions, but it [43].
may be hard to establish their history, and co-occurring A US Alzheimer’s Disease Center longitudinal research
conditions should be identified for intervention. With new program found that of 310 respondents between the ages of
onset memory, visuospatial, language, or executive dys- 62 and 91 years, 4.4 % of respondents had childhood
function, neurodegenerative conditions should be consid- ADHD, as indicated by the WURS, including ten cogni-
ered [32]. Dementia syndromes overlap but memory and tively intact subjects and three cognitively impaired
 D. W. Goodman et al.

Table 2 Differential diagnosis of ADHD traits in older adults

Diagnosis Neurological examination Other clinical investigation Structural MRI findings

Psychiatric conditions Normal Interview for current or past abnormal None

mental status
Symptom screening, e.g. BDI, MADRS,
MDQ, SPRAS/SCAS, GADSS, BPRS
Mild cognitive May be abnormal, dependent MOCA (normal C26) May have regional cortical atrophy
impairment on subtype Neuropsychological testing patterns
Brain MRI ± PET scan
Dementiaa May have apraxia, aphasia ACE–R, Mini-Cog Focal atrophy patterns dependent on type
primitive reflexes, upper Neuropsychological testing of dementia
motor neuron signs, Microangiopathic disease ± lacunar or
Lumbar puncture
parkinsonism hemispheric infacts, cerebral amyloid
Vascular risk factor screen: blood
angiopathy
pressure, HbA1c, cholesterol
Brain MRI ± PET scan
Parkinson’s disease or Atypical parkinsonism, PSP-RS Dependent on subtype: hummingbird
other parkinson-plus asymmetric motor findings, Neuropsychological testing sign (PSP), morning glory sign (PSP),
syndromesb apraxia, vertical gaze palsy; hot cross bun sign (MSA), asymmetric
Orthostatic vitals for autonomic
polyminimyoclonus cortical atrophy (CBS)
dysfunction
Brain MRI ± PET scan
Toxic/metabolic/ May have delirium, focal Examination for stigmata of nutritional Normal or may have mammillary body
infectious/ neurological deficits, deficiency/alcohol use/heavy metals hyperintensities, may show nonspecific
inflammatory peripheral neuropathy, Assay vitamin B12, folic acid, thiamine, white matter changes, mesial temporal
ataxia, ophthalmoplegia hemoglobin, ferritin, thyroid function, hyperintensities, meningeal
electrolytes, liver function, fasting enhancement
glucose, renal function, urea; heavy
metal screen, toxicology, blood alcohol
level
Infectionsc May have delirium, focal Vital signs May be normal or display lesions or
neurological deficits, neck Lumbar puncture inflammation
rigidity
Infectious serology
Brain MRI
Other encephalopathy None or focal deficits Neuropsychological testing May be normal or display
(genetic, Genetic testing encephalomalacia, microhemorrhages,
developmental, diffuse axonal injury
Sleep study
perinatal, trauma, or
head injury) Sleep-deprived EEG
Brain MRI
Presenting features and clinical work-up differentiates ADHD and other mental changes seen in older age
MRI magnetic resonance imaging, MOCA Montreal Cognitive Assessment, ACER–R Addenbrooker’s Cognitive Examination–Revised, PSP-RS
Progressive Supranuclear Palsy Rating Scale, BDI Beck Depression Inventory, MADRS Montgomery–Åsberg Depression Rating Scale, MDQ
Mood Disorder Questionnaire, SPRAS/SCAS Sheehan Patient Rated/Clinician Anxiety Scale, GADSS Generalized Anxiety Disorder Severity
Scale, BPRS Brief Psychiatric Rating Scale, PET positron emission tomography, EEG electroencephalogram, PSP progressive supranuclear
palsy, MSA multiple system atrophy, CBS cortical basal syndrome
a
Alzheimer’s disease, frontotemporal dementia, vascular disease
b
PSP, Lewy Body dementia, multiple system atrophy, corticobasal syndrome
c
Systemic, encephalitis, meningitis, focal subdural/epidural abscess, HIV/AIDS, neurosyphilis limbic encephalitis, other autoimmune
encephalitides

subjects. In this sample, there was no association between a is notable that in the Australian PATH sample, comorbid
WURS positive screen and cognitive impairment. This mood disorders explained the correlation between ADHD
study also investigated the utility of cognitive test profiles symptoms and performance on a cognitive test battery in
to identify older individuals with a history of childhood older individuals. This is consistent with findings that
ADHD. Neuropsychological tests did not differentiate cognitive tests do not reliably distinguish ADHD cases in
WURS-positive from WURS-negative individuals [44]. It younger adults [45].
ADHD in Older Adults: A Review of Evidence and Implications for Care

5 Treatment of ADHD in Older Adults catecholaminergic mechanisms; thus, if using them in older
adults, clinicians should identify and specially monitor
While some studies have included older adults in clinical conditions that might be exacerbated by increased sympa-
trial samples [46], we did not find any clinical trials that thetic tone, including hypertension, arrhythmia, uro-
specifically reported on outcomes for this group beyond the logic/sexual function, narrow angle glaucoma, and poor
fifth decade of life; however, we did find three brief peripheral circulation (e.g. Raynaud’s, vasculopathy).
descriptions of the course of treatment in older adults. Common stimulants such as caffeine or pseudoephedrine
Manor et al. reported on methylphenidate treatment in the may compound the sympathetic effects of ADHD agents.
11 older adults in their sample, noting that ten of them Older adults may have greater risks from side effects such
continued on treatment for at least 2 months, eight reported as appetite reduction, insomnia, dry mouth, tremor exac-
significant improvement, and only mild physical side erbation, urinary retention, or withdrawal fatigue that can
effects occurred that are typical of stimulant treatment [16]. occur with stimulant or atomoxetine therapies. It is not
In a US survey of psychiatrists, of 25 adults with a diag- known whether individuals with cognitive impairment are
nosis of ADHD aged 60–77 years, all had been on medi- at higher risk of adverse effects from stimulants. One study
cation and all but two subjects reported benefit, while 25 % of methylphenidate treatment in Alzheimer’s patients noted
reported side effects [47]. One hundred and forty-nine of that two subjects had serious adverse experiences of
the Norwegian survey participants, who self-reported delusions, agitation, anger, irritability, and insomnia [50].
having ADHD, completed a questionnaire about treatment. With aging, cardiovascular risks of treatment may also
The majority (88 %) had been treated with medications and increase. All subjects receiving stimulants or atomoxetine
64 % of participants were on medication. Those who should be screened for a personal or family history of
remained on medication reported improved attention and arrhythmia symptoms, such as unexplained lightheaded-
better self-efficacy compared with 10 years ago, whereas ness, chest pain, or sudden death in a relative under the age
no improvement was observed in those who had stopped of 30 years [51]. Routine electrocardiogram (EKG) is not
medication or who were medication naive. The self-re- recommended as it may not be sensitive or specific enough
ported mean dose of methylphenidate and amphetamine to identify arrhythmia risk or structural abnormalities.
was 54.1 and 29.5 mg/day, respectively, with methylphe- Catecholaminergic agents can increase heart rate or heart
nidate used most often [48]. contractility, raising concern about their use in the setting
There has been limited evaluation of cognitive effects of of arrhythmia or structural abnormalities. FDA-approved
ADHD medications in older adults. Manor et al. found that prescribing information suggests that symptomatic and/or
eight of nine individuals receiving methylphenidate had severe cardiovascular disease is a contraindication to
improvement on the Test of Variable Attention (TOVA) treatment with amphetamines and atomoxetine; Thus,
[16]. One study of 60 non-ADHD adults with a mean age consultation or cardiac work-up may be advisable wher-
of 61 years suggests that methylphenidate may have less ever an individual is at risk for cardiac disease.
impact on neuropsychological test performance than in Age-related decline in renal or hepatic function could
younger children [49]. theoretically impact the risk or effect of ADHD medica-
Medications that are US FDA-approved specifically for tions. We were only able to find one study that directly
ADHD in adults are the stimulants mixed amphetamine evaluated the pharmacokinetics of a medication used for
salts extended release (XR), OROS methylphenidate, ADHD in older adults. Forty-seven individuals over the
dexmethylphenidate XR, and lisdexamfetamine, as well as age of 55 years were given a single 50 mg dose of lis-
the non-stimulant atomoxetine. The maximum FDA-ap- dexamfetamine. Individuals C75 years of age had a mildly
proved age for use of these medications varies from 55 to elevated maximum serum concentration (Cmax), area under
65 years. These ages are determined by the drug trial the curve (AUC), median time at which the Cmax is
research that capped the inclusion of subjects at a certain observed (Tmax), and mean half life (t‘) but exposure did
age (for example, lisdexamfetamine at 55 years of age, and not correlate with creatinine clearance. There was no clear
mixed amphetamine salts XR at 65 years of age). Clinical correlation between blood pressure or pulse effects of lis-
trials of ADHD interventions also typically exclude indi- dexamfetamine and age [52]. Safety and vital sign
viduals with comorbid conditions, further limiting their parameters in this age group may be effected by normal
generalizability [28]. However, lack of a systematic study age-related decreases in adrenergic sensitivity to sympa-
leaves it unclear how effective stimulants are, or how well thomimetic stimulation [53]. In contrast, a study of D-am-
they are tolerated in older people with ADHD. phetamine administration in individuals with acute stroke
All medications with evidence, from clinical trials, for found a correlation between serum creatinine levels and
effect on ADHD symptoms are thought to act via AUC/mg/kg of amphetamine [54].
 D. W. Goodman et al.

Limited evidence is available to suggest that methyl- presenting with mood or anxiety disorders should be
phenidate could inhibit the metabolism of other medica- screened for ADHD at any age. Clinicians should carefully
tions. Amphetamine is metabolized through several differentially diagnose ADHD, and give particular atten-
pathways, including the cytochrome P450 (CYP) 2D6 tion to comorbid conditions that could be complicated by
isoenzyme. There is evidence to suggest that polymorphic ADHD pharmacotherapy. Psychotherapy and behavioral
variability in liver enzyme activity is not thought to sig- supports should be tailored to individual capacities and
nificantly impact the amphetamine elimination rate [55]. environmental supports.
While it is generally accepted that stimulants can be safely However, it remains unclear whether DSM symptom
coadministered with many other medications, checking for criteria are as appropriate for identifying the syndrome in
interactions in an updated computerized interaction query older adults as they are in younger adults. The longitudinal
is advised. Medications with lower effect size for ADHD study of ADHD adults into older age, with neuropsychi-
include buproprion, a CYP2D6 inhibitor, and atomoxetine, atric evaluation and comparison with non-ADHD controls,
a CYP2D6 substrate, and these may create metabolic drug could clarify optimal criteria for identifying ADHD in the
interactions. Drugs that alter gastrointestinal pH may aging population.
impact absorption of amphetamines, and those that impact Clinical trials of treatment in older adults are needed.
urine pH may significantly impact the rate of renal excre- Clinicians will also benefit from future studies of ADHD
tion of amphetamine [56]. treatment in populations at risk for age-related complica-
The rates of current treatment for ADHD in older tions of these therapies. Monitoring symptom reduction,
adults are not known as no studies relating to this were measuring daily functional improvement, and ensuring
found, but they are likely to be lower than seen in comfort and safety should be goals of ADHD management
younger adults. The NESARC study, in which 35 % of for patients of any age.
those with ADHD were over the age of 45 years, found
Compliance with Ethical Standards
less than 50 % had ever sought treatment and approxi-
mately 25 % had ever received medication [5]. In contrast Funding No sources of funding were used for this publication.
to the belief that ADHD is most commonly diagnosed in
childhood, the average age of first treatment contact was Conflicts of interest Dr. David W. Goodman has received con-
18.4 years. sulting fees and honorarium from WebMD, Medscape, Temple
University, American Professional Society of ADHD and Related
Lacking evidence from systematic study of treatment Disorders, Neuroscience Education Institute, Children and Adults
for older adults with ADHD, clinicians should offer with ADHD Association, McNeil, Teva Pharmaceuticals, Lundbeck,
support developed for younger adults, keeping in mind Janssen (US and Canada), OptumInsight (Ingenix Pharmaceutical
the need for personalization to the specific attentional Services, Inc.), Sunovion, Otsuka Pharmaceuticals, Novartis, Iron-
shore Pharmaceuticals, Rhodes Pharmaceuticals, Neos Therapeutics,
and behavioral concerns of the elderly individual. Med- Thomson Reuters, GuidePoint Global, Med-IQ, Avacat, Pontifax,
ication and/or behavioral and organizational techniques Healthequity Corporation, American Physician Institute for Advanced
should be first-line recommendations, depending on Professional Studies, LLC, Prescriber’s Letter, Consumer Reports,
medical stability, severity of symptoms, and the envi- Major League Baseball, and National Football League.
Dr. Craig Surman has received, in his lifetime, consulting fees or
ronmental demands of the person’s life. Pharmacotherapy honorarium from McNeil, Nutricia, Pfizer, Rhodes, Shire, Somaxon,
has a stronger evidence base for effective reduction of and Takeda. He has also received payments for lectures from Alcobra,
ADHD symptoms than behavioral therapies in children McNeil, Janssen, Janssen-Ortho, Novartis, Shire, and Reed/MGH
[57], but interventions have not been systematically Academy (funded by multiple companies). Royalties have been given
to Dr. Surman from Berkeley/Penguin for FASTMINDS: How to
compared in adults. There is good evidence that behav- Thrive if You Have ADHD (or Think you Might) and from Humana/
ioral (organizational habit) therapies may improve daily Springer for ADHD in Adults: A Practical Guide to Evaluation and
coping strategies, reduce anxiety, and increase daily Management. Additionally, Dr. Surman has conducted clinical
productivity and satisfaction in adults with ADHD [58, research at Massachusetts General Hospital with Abbott, Cephalon,
the Hilda and Preston Davis Foundation, Eli Lilly, Magceutics,
59]. Johnson & Johnson/McNeil, Lundbeck, Merck, Nordic Naturals,
Nutricia, Pamlab, Pfizer, Organon, Shire, and Takeda.
Sara Mitchell and Lauren Elaine Rhodewalt have no conflicts of
6 Conclusions interest to disclose.

To the best of our knowledge, this paper represents the first

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