Pharmacologic Considerations in
the Treatment of ADHD in Adults
Presented by: Ann M. Wheeler, PharmD, BCPP
Date: 3/31/2016
Disclosures and Learning Objectives
• Learning Objectives
Be able to identify first-line treatment
recommendations and treatment alternatives
for adults with ADHD
Disclosures: Dr. Ann Wheeler has nothing to disclose.
Pharmacologic Treatment of Adult ADHD
• Review
• Background information and clinical
manifestations of adult ADHD
• Treatment alternatives
• Clinical pearls and treatment
recommendations for stimulants and
non-stimulants
Background
• Majority of people diagnosed with ADHD
in childhood continue to meet criteria for
the disorder as adults
• Associated with impairment in occupational,
academic, and social functioning.
• Prevalence estimated to be 4.4% in the U.S.
• Characterized by symptoms of inattention,
impulsivity, and restlessness, resulting in
functional impairment.
Clinical Manifestations
The predominant features of ADHD in adults differ
from typical ADHD features in children.
Symptoms of hyperactivity or impulsivity are less
obvious in adults (impulsivity may be seen in
verbalization rather than physical behavior) and
symptoms of inattention are more prominent.
Clinical Manifestations
Inattention:
•
Problems remaining focused on a task, especially for
long periods
•
Difficulty in organizing activities, prioritizing tasks,
following through and completing tasks, forgetfulness,
and time management
•
Adults with ADHD will often report that tasks are
finished only at deadlines, often late or even not at all
•
Increased problems related to driving, including
increases in driving errors, traffic tickets, and speeding
may be related to attention deficits
Clinical Manifestations
Impulsivity:
•
Characterized by excessive involvement in activities or
speech that has a high potential for consequences
•
Often results in more serious consequences than during
childhood and may include premature termination of
relationships or quitting jobs
•
Impulsivity can also contribute to driving errors, traffic
tickets and speeding
Clinical Manifestations
Hyperactivity:
•
Rather than overly hyperactive, adults with ADHD will
seem or report feeling fidgety or restless.
•
May report talking too much and/or interrupting others
Clinical Manifestations
Executive Dysfunction:
•
•
The following may be deficient in adults with ADHD
•
Working memory
•
Task-shifting
•
Self-monitoring
•
Initiation
•
Self-inhibition
These deficits contribute to the inattention problems
characteristic of adult ADHD (e.g. remaining focused,
organization, prioritization)
Clinical Manifestations
Emotional Dysregulation:
•
Mood lability, irritability, anger outburst, low frustration
tolerance, and motivational deficits are commonly seen
in adults with ADHD though not specific to the disorder.
Differential Diagnosis
Depression
• ADHD shares with depressive disorders a diminished ability to
think or concentrate, poor motivation to undertake activities, and
indecisiveness. Depression can be distinguished from ADHD in
adults by a typically later onset and episodic course.
Mania
• ADHD shares with mania distractibility, impulsivity, and
increased talkativeness. Mania can be distinguished from ADHD
in adults by a typically later onset and episodic course.
Differential Diagnosis
Anxiety Disorders
• ADHD is often accompanied by anxiety. Patients with anxiety
disorders can be distracted by the focus of the disorder, which
can present similarly to the distractibility seen in ADHD. In
contrast to ADHD, distraction with an anxiety disorder only
occurs in the presence of the focus of that disorder (e.g.
preoccupied with a specific fear). The onset of anxiety disorders
may be later than the onset of ADHD in adults.
Substance Use Disorders
•
Cognitive and behavioral impairments can be seen in both
ADHD and in SUDs. Acute impairments in SUDs, however,
occur only in the context of substance use.
Treatment Overview
Short-term clinical trials of pharmacotherapy in
adults with ADHD has shown efficacy in
reducing ADHD symptoms and improving daily
function.
Evidence of long-term symptom reduction is
largely from observational studies, which also
suggest some benefit in functioning, including
work performance, and in self-esteem.
Treatment Overview
Stimulants
• Most extensively tested and commonly prescribed
medications for ADHD across the lifespan.
• MOA in ADHD is unknown, but most likely involves increased
intrasynaptic concentrations of dopamine and norepinephrine.
Non-Stimulants
• Non-stimulant medications with efficacy in adult ADHD
include atomoxetine, bupropion, and tricyclic antidepressants.
• Comparison of effect sizes in clinical trials suggests that
stimulant medications are more efficacious.
Clinical Pearls—Stimulants
• There does not appear to be a substantial advantage in
efficacy or side effects of preferentially using
methylphenidate rather than amphetamine products, or vice
versa.
• Choice of immediate or long-acting stimulant preparation is
often dependent upon patient preference, cost, needed time
of coverage, and/or concern about the potential for
abuse/diversion (long-acting agents may be less prone to
abuse/diversion)
Clinical Pearls—Stimulants
• Once a particular stimulant preparation is selected, it is
started at low dose and titrated up at intervals ranging from
weekly to monthly or longer.
• Because the attention symptoms characterizing adult ADHD are often
subtle, more extended periods are often necessary to fully evaluate the
effectiveness of each dose
• Titration continues until one of the following criteria are met:
• No room for improvement
• Intolerable adverse events
• Maximum dose limits
Clinical Pearls—Stimulants
• At each visit, prescribers should check:
• Report of positive and negative effects of the medication
• Duration of these effects following each dose
• Experience of non-therapeutic reinforcing effects (e.g. euphoria)
• If an inadequate response to one stimulant is seen, the
patient can be switched immediately (no tapering/washout
necessary) to another stimulant preparation
Adverse Effects
Side effects of stimulants reported in adults treated
for ADHD include:
•
Dry mouth
•
Insomnia
•
Edginess/irritability
•
Dysphoria
•
Diminished appetite
•
Weight loss
•
Headache
Adverse Effects
•
A meta-analysis of randomized trials found that 10% of
adults with ADHD treated with stimulant medications
discontinued the medication due to adverse events.
•
Progressive titration to an optimally effective dose helps
minimize side effects (use lowest dose possible)
Adverse Effects
•
Other adverse effects:
•
Psychosis: Has occurred with stimulant abuse and in treatment with
stimulants in patients with a vulnerability to psychosis
•
Cardiovascular effects: BP and HR should be monitored upon initiation
and over the course of treatment. Consistent elevations in systolic and
diastolic BP and HR have been found to result from stimulant use in
adults.
•
•
Research on the relationship between treatment and serious cardiac events
has found mixed results:
•
One population-based cohort study did not find an association between stimulant
treatment and the risk of sudden CV events among young and middle-aged adults
•
Another retrospective analysis found a 1.8-fold increase in sudden death or
ventricular arrhythmia
Priapism: Priapism is a rare complication of methylphenidate
Misuse and Abuse
Amphetamine = Bennies, Black Beauties, Crosses, Hearts,
LA Turnaround, Speed, Truck Drivers, Uppers
•
Common ways taken: swallowed, snorted, smoked, injected
Methylphenidate = JIF, MPH, R-ball, Skippy, The Smart
Drug, Vitamin R
•
Common ways taken: swallowed, snorted, smoked, injected,
chewed
National Institute on Drug Abuse: www.drugsabuse.gov
Misuse and Abuse
Misuse and Abuse—CVS Survey
• Half of all the students surveyed in the CVS report said they took
stimulants to assist with pulling an all-night study session or
improving their academic performance.
• About 24% said they misused or abused these drugs to improve
work performance at a job.
• 1 in 5 college students reported abusing prescription stimulants.
• About 56% of those surveyed said it’s easy to obtain prescription
stimulants not intended for them.
• Among those who have a prescription, 52% said they had been
pressured by friends into sharing or selling their medication
• Of the students with legitimate prescriptions, 28% admit to selling
and/or sharing their pills
Non-Stimulants
Atomoxetine
•
Inhibits presynaptic norepinephrine reuptake, resulting
in increased synaptic norepinephrine and dopamine
•
Modestly more effective than placebo in reducing the
core symptoms of adult ADHD
•
Adverse effects: dry mouth, insomnia, nausea,
decreased appetite, constipation, decreased libido,
erectile dysfunction, urinary hesitancy, dizziness, and
sweating (discontinuation due to adverse effects
compared to placebo = 17.2% vs. 5.6%)
Non-Stimulants
Bupropion
•
Antidepressant with mixed catecholaminergic effects
•
Positive results have been found for both the QD (XL)
and BID (SR) dosed preparations. Compared to
placebo, bupropion led to a higher response rate and
greater reduction in inattentive and overall ADHD
symptoms in adult patients.
•
Adverse effects: dry mouth, insomnia, nausea,
dizziness, anxiety, dyspepsia, sinusitis, and tremor.
May increase risk of seizures, particularly at higher
doses and shorter-acting formulations.
Non-Stimulants
TCAs
•
Have demonstrated efficacy in adult ADHD
•
Advantages: lack of abuse liability, single daily dosing,
efficacy in co-occurring anxiety and depression
•
Less effective and more poorly tolerated compared to
stimulants, atomoxetine or bupropion
•
Administration: Start at a low dose and titrate up slowly
Non-Stimulants
Alpha-2 Agonists
•
Little is known about the efficacy, safety and tolerability
of alpha-2 adrenergic agonists clonidine and guanfacine
in adults with ADHD
•
Considered to be 4th line following stimulants,
atomoxetine and antidepressants
Other Medications
•
Venlafaxine—may be mildly efficacious, only small
studies
•
SSRIs—only small studies, may be effective
•
MOAIs—have shown mixed results, ADHD patients are
likely poor candidates for this drug class
•
Selegiline—no better than placebo
•
Modafinil—little evidence of efficacy in adult ADHD
•
Medication Augmentation—not currently supported
by evidence in adult ADHD
Duration and Continuity
When is the medication needed
•
Vocational activities, educational activities or all
activities
•
Some may benefit or tolerate drug holidays (e.g.
weekends)
•
Some may require treatment for a limited time period,
others may need them indefinitely
Treating ADHD in Co Occurring Disorders
SUD
•
Treatment of ADHD with a stimulant does not appear to
affect the likelihood of subsequent SUD development
•
•
Neither increasing SUD risk nor having a protective effect
Clinical trials of stimulant treatment in ADHD patients
with an active SUD have found mixed efficacy results,
with only 1 of 4 trials showing a reduction in ADHD sx in
the stimulant-treated group compared to placebo
Treating ADHD in Co Occurring Disorders
Depression
•
Bupropion and TCAs have demonstrated efficacy, with
bupropion often better tolerated.
Anxiety
•
Combination stimulant and an SSRI are generally
effective. TCAs provide a secondary alternative.
Treatment Selection
•
Adults with ADHD
•
•
•
ADHD and known h/o SUD
•
Atomoxetine or bupropion is first-line
•
Long-acting stimulants are second-line with careful monitoring
for signs of misuse, diversion or addiction
ADHD and active SUD
•
•
Treat the SUD first prior to initiating pharmacotherapy for ADHD
ADHD and depression
•
•
Stimulants are generally first-line; non-stimulants are secondline
Bupropion is first-line; Stimulant + an SSRI is an alternative
ADHD and anxiety
•
Stimulant + an SSRI
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
Focalin and generic
equivalents
0.5 - 1 hr
5 – 6 hrs
5 mg
bid
Inc total
daily dose
by 10 mg
at weekly
intervals
15 mg bid
(maximum 20
mg bid)
Focalin XR and
generic equivalents
0.5 - 1 hr; a
2nd peak
occurs ~6.5
hrs p dose
12 hrs
10 mg
qd in
AM
Inc daily
dose by
10 mg at
weekly
intervals
30 mg qam
(maximum 40
mg qd)
Dexmethylphenidate
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
3 – 5 hrs
10 mg bid
before
breakfast
and lunch
Inc total
daily dose
by 5 or 10
mg at
weekly
intervals
40 to 60 mg
per day in 2 or
3 divided doses
Methylphenidate—Shorting acting
Ritalin and generic
equivalents
Methylin, chewable
Methylin, oral
solution
< 1 hr;
delayed if
high fat
meal
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
Methylphenidate—Intermediate acting
Ritalin SR and
generic equivalents
< 1 hr
4 – 8 hrs
20 mg qd
in AM
Inc daily
dose by 10
mg at
weekly
intervals
40 to 60 mg
per day in AM
Metadate ER and
generic equivalents
< 1 hr
4 – 8 hrs
10 mg bid
Inc daily
dose by 10
mg at
weekly
intervals
40 to 60 mg
per day in AM
Stimulants
Medication
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
< 1 hr; 2nd
peak occurs
~4.5 hrs p
dose
8 – 12 hrs
20 mg qd
in AM
Inc daily
dose by 10
or 20 mg at
weekly
intervals
40 to 60 mg
per day in AM
< 1 hr
8 – 12 hrs
20 mg qd
in AM
Inc daily
dose by 10
or 20 mg at
weekly
intervals
40 to 60 mg
per day in AM
Onset of
Initial
Effect
Methylphenidate—Long acting
Metadate CD and
generic equivalents
Quillivant XR oral
suspension
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
Methylphenidate—Long acting
Ritalin LA and
generic equivalent
< 1 hr; 2nd
peak occurs
~5.5 hrs p
dose
8 – 12 hrs
10 or 20
mg qd in
AM
Inc daily
dose by 10
mg at
weekly
intervals
40 to 60 mg
per day in AM
Concerta and
generic equivalents
< 1 hr;
plateau at 1
– 4 hrs and
peak at 6
hrs p dose
10 – 12
hrs
18 or 36
mg qd in
AM
Inc daily
dose by 18
mg at
weekly
intervals
54 to 72 mg
per day in AM
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
10 – 12
hrs
30 mg
patch on
for 9 hrs &
off for 15
hrs each
day
Inc to next
higher dose
at weekly
intervals;
Available
strengths:
10 mg, 15
mg, 20 mg,
and 30 mg
per 9 hrs
60 mg patch on
for 9 hrs and
off for 15 hrs
each day
Methylphenidate—Long acting
Daytrana
transdermal patch
< 2 hrs
Apply 2
hrs before
needed
onset
Stimulants
Medication
Onset of
Initial
Effect
Initial
Dose
Titration
Maintenance
Dose
4 – 6 hrs
5 mg bid
Inc total
daily dose
by 5 mg at
weekly
intervals
20 mg bid
6 – 8 hrs
5 mg bid
Inc total
daily dose
by 5 mg at
weekly
intervals
40 mg qd in AM
Duration
of Effect
Dextroamphetamine—Shorting acting
Generics
< 1 hr
Dextroamphetamine—Long acting
Dexedrine spansule
and generic
equivalents
< 1 hr
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
Dextroamphetamine and Amphetamine (mixed salts)—Shorting acting
Adderall and generic
equivalents
< 1 hr
4 – 6 hrs
5 mg qd
or bid
Inc total
daily dose
by 5 or 10
mg at
weekly
intervals
40 to 60 mg
per day in 1 to
3 divided doses
Dextroamphetamine and Amphetamine (mixed salts)—Long acting
Adderall XR and
generic equivalents
< 1 hr
8 – 10 hrs
20 mg qd
in AM
Inc total
daily dose
by 10 mg at
weekly
intervals
40 to 60 mg qd
in AM
Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
< 1 hr;
onset
delayed if
taken with
food
~10 hrs
30 mg qd
in AM
Inc total
daily dose
by 10 or 20
mg at
weekly
intervals
30 to 70 mg qd
in AM
Lisdexamfetamine
Vyvanse
Non-Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
1 to 2
weeks
24 hrs
40mg qd
Inc after 3
or more
days to 80
mg; after 2
to 4 weeks
may
increase to
100 mg per
day
80 mg qd or in
two equally
divided doses
(maximum 100
mg per day)
Atomoxetine
Strattera
Non-Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
12 hrs
0.1 mg qd
at bedtime
Inc daily
dose by 0.1
mg at
weekly
intervals
0.1 to 0.3 mg
qd or in two
divided doses
(maximum 0.4
mg/day)
8 to 14
hrs
1 mg qd
Inc daily
dose by 1
mg at
weekly
intervals
1 to 4 mg qd
Clonidine extended-release
Kapvay
1 to 2
weeks
Guanfacine extended-release
Intuniv
1 to 2
weeks
Non-Stimulants
Medication
Onset of
Initial
Effect
Duration
of Effect
Initial
Dose
Titration
Maintenance
Dose
Wellbutrin SR or
generic equivalents
1 to 2
weeks
12 hrs
150 mg
qd in AM
After 3 days
increase to
150 mg bid
150 mg bid
(maximum
200mg bid)
Wellbutrin XL or
generic equivalents
1 to 2
weeks
24 hrs
150 mg
qd in AM
After 3 days
increase to
300 mg qd
300 mg qd
(maximum 450
mg qd)
Bupropion
The End
Next Week:
TBD