Download Are Stimulants Appropriate in the Elderly?

7/15/2015
Are Stimulants Appropriate in
the Elderly?
Cherry W. Jackson, Pharm.D., BCPP, FASHP
Professor of Pharmacy, Auburn University
Professor of Psychiatry and Behavioral Neurobiology
University of Alabama, Birmingham
Disclosure/Conflict of Interest
• I, Cherry W. Jackson, have not actual or
potential conflict of interest in relation to this
program.
• Programming offered by Auburn University
Harrison School of Pharmacy shall exhibit
balance, providing the audience information
of different perspectives from which to
develop an informed professional opinion
Objectives
• Describe indications for the use of stimulants
in the elderly
• Discuss prescribing limitations for stimulants
in the elderly population
• Identify comorbid medical conditions that
warrant concern when using stimulants
• Specify possible drug interactions that should
be monitored for in patients taking stimulants
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Question 1
• Which of the following are unapproved but
accepted reasons for using stimulants in
elderly patients?
A.
B.
C.
D.
Schizophrenia
Anxiety
Apathy
Insomnia
Question 2 and 3
• Mr. Z. is admitted to the hospital post stroke. He has
depression and apathy and he is not eating or drinking
currently and he will not be able to go to rehab until he
is able to eat on his own. His other illnesses include
ventricular arrhythmia, myocardial infarction, and
chronic renal failure. His current height is 6 foot,
weight is 142 pounds, blood pressure is 180/100,
heart rate is 110, respiratory rate is 22. Current
medications are: digoxin, warfarin, lisinopril, losartan,
lasix, and sertraline. Mr. Z’s physician would like to
initiate methylphenidate 2.5 mg so that the patient can
be moved to rehab.
Question 2 (cont.)
• Which of the following medical conditions warrant concern
when using stimulants?
• A. Stroke
• B. Depression
• C. Apathy
• D. Ventricular arrhythmia
• E. Chronic Renal failure
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Question 3
• If a stimulant were initiated in Mr. Z. which of the
following might you be concerned about causing
a drug interaction?
• A. Digoxin
• B. Warfarin
• C. Lisinopril
• D. Losartan
• E. Lasix
• F. Sertraline
Stimulants
• Stimulants release dopamine from the brain
• Methylphenidate increases dopamine
transport
• Dextroamphetamine binds the dopamine
transporter.
• Stimulant effect occurs in 30-45 minutes
• Increased alertness, insomnia, euphoria,
decreased appetite
Chukwujekwu CC. Geriatric Medicine.
2009 430-431.
Use of Stimulants in the Elderly
• Stimulants in the elderly:
– Promote wakefulness
– Increase energy
– Improve attention
• Pharmacists should be aware of possible side
effects/safety concerns
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Use of Stimulants in the Elderly
• The elderly patient’s changing physiology
presents treatment challenges
• Decreased response to antidepressants
• Stimulants may benefit the medically ill
Franzen JD, et al. Current Psychiatry. 2012;11(1)23-32.
Stimulants
• Starting doses in older adults
– Methylphenidate 5 mg/day
– Dextroamphetamine 5 mg/day
•
•
•
•
Peak 2-4 hours
Vital signs evaluated 2-4 hours after dose
“Failed trial” no response after 20 mg/day
Response that wanes can be repeated
Chukwujekwu CC. Geriatric Medicine. 2009 430-431.
Use of Stimulants in the Elderly
• Stimulants are used to treat:
– Attention Deficit Hyperactivity Disorder (ADHD)
– Apathy
– Fatigue
– Falls
– Depression
Franzen JD. Current Psychiatry. 2012; 11(1) 23-32.
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Indications for Stimulants
• Attention Deficit Hyperactivity Disorder
(ADHD)
– 8% of children, 4% of adults
– Characterized by impulsivity, motor restlessness,
inattention
– Societal burden
– Lack of data on ADHD in older adults
Lazare J. ADHD in Older Adults. Todays
Geriatric Medicine. 2014
Indications for Stimulants
• Attention Deficit Hyperactivity Disorder
– Stimulants are first line treatments for ADHD
– Improvement in symptoms compared to placebo.
– Benefits of treatment often outweigh risks
– Screen carefully
Lazare J. ADHD in Older Adults. Todays
Geriatric Medicine. 2014
Forgetfulness or ADHD?
• Mr A., age 68 is an attorney who presents for
evaluation after he identified common features in
friends that have attention-deficit/hyperactivity
disorder (ADHD). In grade school, Mr. A’s teacher
told him that he employed very little effort and
was not meeting his potential, although he
performed exceptionally well. He reports similar
experiences throughout his education and says
he was careful to select classes that were
interesting, but did not required demanding
projects or burdensome homework.
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Forgetfulness or ADHD?
• In law school, he felt academically challenged for
the first time but realized he had limited study
skills. Mr. A. graduated in the top 26th percentile
of his class using “an unbelievable amount of
effort compared with other students.”
• Mr. A. describes significant impairment in
organizational skills and ability to keep track of
time, procrastination, completion of tasks, and
substantial distractibility during conferences. He
says he has difficulty reading briefs depending on
his emotional connection to the subject matter.
Forgetfulness or ADHD?
• Family history revealed that his mother likely had
undiagnosed ADHD. He recently married and his wife
encouraged him to seek treatment for “forgetfulness”.
Mr. A. maintains a busy, successful law practice but has
become increasingly frustrated by his inability to follow
through on simple tasks that could help grow the
practice and generate revenue.
• Mr. A. has an elevated score on the ADHD Symptom
Rating Scale. He is referred to his primary care
physician to evaluate his general health before
beginning medication. At follow-up, Mr. A was started
on lisdexamfetamine 20 mg/d titrated to 40mg/d.
Forgetfulness or ADHD?
• On subsequent visits he reports improved
symptoms without side effects. His vital signs
are normal and he reports feeling more
productive in his work and achieving
significant improvement in the day-to day
operations of his practice.
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ADHD and Stimulants
• Patients tend to be:
– High functioning
– Professional success
– Academic success
– Inefficient learning
– Distraction
Franzen JD, et a. Current Psychiatry
2012; 11(1) 23-32.
ADHD and Stimulants
• Diagnosis and treatment of ADHD improves
– Functional impairment
– Quality of life
Franzen JD. Current Psychiatry .2012;11(1) 2332.
Indications for Stimulants
• Apathy
– Apathy is a loss of motivation, interest, or
initiative
– Common in dementia of Alzheimer’s type (DAT)
– Impairment in activities of daily living
– Increased burden for caregiver
Ishii S, et al. J Am Med Dir Assoc 2009;
10:381-93.
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Apathy vs. Depression
• Apathy is not depression
• Apathy and depression symptoms overlap
• Significant decrease in glucose metabolism
with apathy
• Depression was associated with
hypometabolism
Franzen JD, et al. Current Psychiatry. 2012;
11(1):23-32.
Apathy vs. Depression
• Apathy may be more prominent in the elderly
• Treatment with SSRI’s may lead to apathy
• Symptoms include:
– Fatigue, inattentiveness, forgetfulness, wordfinding difficulty, mental slowing
Mehta M et al. Int J Geriatr Psychiatry 2008;
23:238-43.
No Interest in Life
• Mr. B., age 76, has dementia of the Alzheimer’s
type. His family brings him to a psychiatrist
because Mr. B. exhibits a generalized loss of
interest. His history reveals a gradual onset of
memory problems with a steady decline. Current
deficits include problems with forgetfulness,
misplacing items, increasing difficulty with
names, occasional repetitiveness, and mild word
finding difficulty. His family complains that Mr. B
does not take care of himself, sits all day long, is
not interested in his favorite TV shows, is
indifferent to his physical health, is not interested
in catching up with friends and has been doing
very little from day to day.
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No Interest in Life
• He does not seek food but cleans his plate when
served. His family became concerned when Mr. B
showed no excitement in going to his grandson’s
baseball games, which he had previously enjoyed. Mr.
B. denies any concerns and scores a 3 out of 15 on the
Geriatric Depression Scale. Mr. B’s family rated him 4
on the same scale.
• On the Apathy Evaluation Scale (AES), he scores 46
(moderate severity). We start methylphenidate, 5 mg
administered in the morning and early evening (5 pm).
Subsequent conversations 2 weeks later with Mr. B’s
family reveals Mr. B’s interest levels have improved and
reported no side effects.
No Interest in Life
• Methylphenidate increased to 10 mg twice a
day. Mr. B has remarkably improved hygiene
one month later and is more engaged in the
interview. He scored a 32 (mild severity) on
the AES and the family notes that he is
interested in watching his grandson play
baseball. During this treatment, we did not
change Mr. B’s other medications-donepezil,
10 mg/day, and bupropion, 150 mg/day.
Apathy and Stimulants
• Open label study of patients with DAT
– Methylphenidate 10 – 20 mg/day
– Improvement in AES Scores
• Hermann et al.
– Methylphenidate 20 mg/day vs placebo
– Improvements in AES scores
• Double-blind, placebo-controlled crossover study
– Dextroamphetamine 20 mg/day
– Improvement in NPI-apathy subscales
Padala PR, et al. Ann Pharmacother. 2010; 44(10):1624-32. Herrmann N
et al. J Clin Psychopharmacol. 2008; 28(3):296-301. Huey ED et al. J Clin
Psychiatry2008;69(12)1981-82.
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Stimulants and Depression
• Depression
– Affects more than 6.5 million Americans over age
65
– Treat depression acutely
– Rapidly acting
– Medically ill/medically fragile
Huffman JC et al. Prim Care Companion J
Clin Psychiatry. 2004; 6(1):44-46.
Stimulants and Depression
• Monoamine hypothesis-depression results
from decreased norepinephrine and
serotonin.
• Increasing these neurotransmitters in the
prefrontal cortex could improve depressive
symptoms
Chukwujekwu CC et al. Geriatric Med. 2009;
430-431.
Depression in the Medically Ill
• Mr. C. is a 71 year old man with a history of
chronic obstructive pulmonary disease (COPD),
hypertension, and hypercholesterolemia who was
admitted to the hospital for the treatment of a
COPD exacerbation. When his symptoms of
COPD worsened on the third day of
hospitalization, he was transferred to the
intensive care unit and intubated. He remained
intubated for 6 years, and his respiratory function
improved enough to allow for extubation.
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Depression in the Medically Ill
• Mr. C slowly recovered, but by the fifth day of
hospitalization, he appeared withdrawn,
apathetic, and dysphoric. His appetite had
waned, as had his participation in his daily
regimen of chest physical. Psychiatric
consultation was requested for evaluation of
depression. Finding symptoms of major
depressive disorder, poor oral intake, and limited
participation in his medical and rehabilitative
care, the consultant psychiatrist considered
prescribing a psychostimulant.
Depression in the Medically Ill
• Mr. C. would be a good candidate for
psychostimulant treatment of his depressive
symptoms based on the information presented.
He had no obvious contraindications to the use of
stimulants, and he would most likely have
benefited from their rapid onset of action. This
rapid effect would have been particularly
important for him because his poor appetite and
inability to participate in his care were
contributing to a suboptimal medical outcome.
Depression in the Medically Ill
• He could have been started at either 2.5 or 5
mg of dextroamphetamine or
methylphenidate. His vital signs should have
been monitored closely (especially during the
first few hours following a dose), given his
medical fragility. Both the literature on
psychostimulants and our experience suggest
that he would have tolerated this treatment
well and had an excellent change of
responding rapidly to treatment.
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Stimulants and Depression
• Randomized placebo-controlled trial of
methylphenidate in the elderly
• Three case studies of methylphenidate as an
antidepressant in elderly patients -no
significant side effects
• Case reports with adjunctive venlafaxine,
mianserin, citalopram, and fluoxetine
Kaplitz S. J Am Psych. 1975; 23:271-76.
Jansen IH. J Am Geriat 2001;149:474-76.
Katon W. Am J Psychiatry 1980;137:963-65.
McLeod . J Pain Symptom Manage 1988; 16:193-98.
Lingam V. J Clin Psychiatry 1988;149:151-53.
El-Mallakh R.Bipolar Disorders. 2000;2:56-59.
Bader G. J Clin Psychopharmacol 1988; 18:255-56.
Sekine Y. J Clin Psychopharmacol 2000;20:584-85.
Lavretsky H. J Clin Psychiatry 2003;64:1410-14.
Stimulants and Depression
• Double-blind, placebo controlled trial of
methylphenidate and citalopram
• 143 patients, average age 69.7 yo
– Methylphenidate plus placebo (48)
– Citalopram plus placebo (48)
– Citalopram plus methylphenidate (47)
• Citalopram dose 20-60 mg; Methylphenidate
5-40 mg
Lavretsky H, et al. Am J Psychiatry:, Feb 2015
Stimulants and Depression
Scale (HAM-D) Score Over Time, by Treatment Condition,
Among Patients Receiving Citalopram, Methylphenidate, or
Their Combination
25
Citalopram plus placebo
HAM-D Score
20
Methylphenidate plus placebo
a
Citalopram plus methylphenidate
15
b
b
b,c
10
b,c
c
c
b,c
c
b,c
5
0
a
Baseline
1
2
3
4
6
8
10
12
14
16
Study Week
Statistically significant difference between citalopram plus placebo and
methylphenidate plus placebo, p,0.05.
b
Statistically significant difference between citalopram plus placebo and
citalopram plus methylphenidate, p,0.05.
c
Statistically significant difference between methylphenidate plus placebo and citalopram plus methylphenidate, p,0.05.
Lavretsky H. Am J Psychiatry 2015
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Stimulants and Depression
• Patients who might benefit from stimulants
– Terminal cancer and depression
– Post-stroke depression
– Bipolar depression
– HIV
– Poor weaning from mechanical ventilation
– Medically fragile patients
– Poor nutritional intake
– When rapid recovery is needed
Franzen JD. Current Psychiatry. 2009;11(1)23-32.
Huffman JC.Prim Care Companion J Clin Psychiatry. 2004;6(1):44-46.
Chukwujekwu CC. Geriatric Med 2009. 430-431.
Indications for Stimulants
• Fatigue
– Frequently seen in patients with medical illnesses
• Mood disorders
• Sleep disturbances
• Side effect of interferon alpha
– Rule out:
• Hypothyroidism
• Anemia
• Electrolyte disturbances
Franzen JD. Current Psychiatry. 2009; 11(1):23-32.
Indications for Stimulants
• Falls
– Decreased cognition
– Decrease in gait stability
– Double-blind placebo-controlled trial
• Methylphenidate 20 mg/day
• Improves executive function
• Improves gait stability
Franzen JD. Current Psychiatry. 2009; 11(1):23-32
J American Geriatrics Society. 2008;56(4):695-700.
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Safety Concerns with Stimulants
• The FDA issued warnings in 2007 concerning
cardiovascular effects
• Stimulants can increase heart rate and blood
pressure
• The FDA reversed its warning in 2011
Westover AN. BMC Cardiovascular Disorders 2012;12:41-51.
Safety Concerns
Author
Year
Study Type/Drugs Data
Source
Population
Holick
2009
Retrospective,
matched cohort/
atomoxetine,
methyphenidate,
amphetamine,
mixed salts
18 years or
1. CVA
older,
2. TIA
atomoxetine
initiators
(n=21,606)
matched to
ADHD
medication
initiators
(n=21,606)
Health
insurance
database
(Ingenix
Research
DataMart)
Outcome
Variable
Result/
Conclusion
No increased risk of
CVA or TIA with
atomoxetine
compared to
stimulants.
Increased risk of TIA
with ADHD
medication
compared to general
population (hazard
ration 3.44, 95%
confidence interval
1.13-10.6).
Holick CN. J Clin Psychopharmacol 2009;29:453-460.
Safety Concerns
Author
Year
Study Type/
Drugs
Habel
2011
Retrospective
matched cohort/
amphetamines,
methylphenidate,
pemoline,
atomoxetine
Data Source
Population
Outcome Result/
Variables Conclusion
Tennessee
Medicaid,
health insurance
databases
(Kaiser
Permanente
California and
Optimum
Insight
Epidemiology)
HMO Research
Network, state
death records,
National Death
Index
Adults 2564 years
old, ADHD
medication
users
matched to
nonusers
(806182
personyears)
1.MI
2.Sudden
Cardiac
Death
3.Stroke
No increased risk
of serious
cardiovascular
events
(MI/SCD/stroke)
for current users
compared to
nonusers
(adjusted rate
ratio 0.83,95%
confidence
interval 0.72-0.96)
Habel LA. JAMA 2011;306:2673-2683.
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Author
Year
Schelleman
2012
Study Type
Drugs
Data Source
matched cohort/
methylphenidate
states) and
health
insurance
database
(HealthCore)
Population
Outcome
Variable
Safety
Concerns
Retrospective
Medicaid (5
18 years and 1.Sudden
older
methylpheni
date users
(n=43,999)
matched to
nonusers
(n=175,955)
death/vent
ricular
arrhythmia
2.Stroke
3.MI
4.Stroke
Result/
Conclusion
Increased risk
of sudden
death or
ventricular
arrhythmia for
current users
(adjusted
hazard ratio
1.84 95%
confidence
interval 1.33 to
2.55). No
increase risk of
stroke MO or
composite
stroke/MI.
Schelleman H. Am J Psychiatry 2012; 169:178-185.
Side Effects
• Less common side effects include:
– Anxiety
– Insomnia
– Hallucinations
– Anorexia
– Delirium
– Palpitations
– Headache
– Glaucoma
Chukwujekwu CC. Geriatric Med. 2009 430-431.
Drug Interactions
• Drug-drug interactions
– MAOI:methylphenidate
– Warfarin:methylphenidate
– Tricyclic antidepressants:stimulants
Chukwujekwu CC. Geriatric Med. 2009 430-431
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Prescribing Limitations
• Stimulants are schedule II controlled
substances
• DEA allows 90 day supply
• Prescription is for legitimate medical purpose
• Must provide written instructions
• Must indicate the earliest fill date
• Multiple prescriptions are permissible in state
laws
Franzen JD. Current Psychiatry. 11(1):23-32.
Controversies
• Efficacy yesterday vs. today
• Interest in completing new research?
• Precautions
– Stimulant misuse
– Careful use
– Balance of risks and benefits
Chukwujekwu CC. Geriatric Med. 2009 430-431
Controversies
• Low risk of misuse and dependence
• Drug dependence
– 18-29 years
– 30-40 years
– 45-64 years
– 65 and over
4.1%
3.5%
1.9%
0.2%
Chukwujekwu CC. Geriatric Med. 2009 430-431
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Conclusion
• Use stimulants with care
• Balance risks and benefits
Chukwujekwu CC. Geriatric Med. 2009 430-431
Question 1
• Which of the following are unapproved but
accepted reasons for using stimulants in
elderly patients?
A.
B.
C.
D.
Schizophrenia
Anxiety
Apathy
Insomnia
Question 2 and 3
• Mr. Z. is admitted to the hospital post stroke. He has
depression and apathy and he is not eating or drinking
currently and he will not be able to go to rehab until he
is able to eat on his own. His other illnesses include
ventricular arrhythmia, myocardial infarction, and
chronic renal failure. His current height is 6 foot,
weight is 142 pounds, blood pressure is 180/100,
heart rate is 110, respiratory rate is 22. Current
medications are: digoxin, warfarin, lisinopril, losartan,
lasix, and sertraline. Mr. Z’s physician would like to
initiate methylphenidate 2.5 mg so that the patient can
be moved to rehab.
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Question 2 (cont.)
• Which of the following medical conditions warrant concern
when using stimulants?
• A. Stroke
• B. Depression
• C. Apathy
• D. Ventricular arrhythmia
• E. Chronic Renal failure
Question 3
• If a stimulant were initiated in Mr. Z. which of the
following might you be concerned about causing
a drug interaction?
• A. Digoxin
• B. Warfarin
• C. Lisinopril
• D. Losartan
• E. Lasix
• F. Sertraline
Questions
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