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96 Substance Use in Older Adults
dizziness, abdominal pain, diarrhea, dysuria, vision problems, slurring
of speech, or tremors. She did not sustain any other injuries, including
head injuries, in the fall. Before the onset of symptoms, for 2 days, she
had been taking 400 mg of ibuprofen three times a day for migraine
headaches. She had been managing the migraines this way for many
years, and says that she used ibuprofen two to three times a day for 10–
15 days every month. She has a history of hypertension treated with oral
atenolol 50 mg daily and peripheral neuropathy treated with oral gabapentin 300 mg three times daily.
Ms. McGraw reported a history of major depressive disorder and
generalized anxiety disorder. For these conditions, for the past 20 years,
her primary care physician prescribed oral escitalopram 10 mg daily, oral
doxepin 300 mg at night, and oral clonazepam 2 mg twice a day. She
reported no psychiatric hospitalizations or suicide attempts. She was
unable to recall her past medication trials for depression and anxiety.
Ms. McGraw reported drinking two glasses of wine in the evening
for the past 10 years. She agreed that the wine consumption was part of
her coping with anxiety, along with the clonazepam. She denied any
blackouts, withdrawal tremors, or seizures. She did not describe any
memory problems, and she can drive, do the household chores and
cooking, and manage her finances, medications, and physician appointments on her own without any issues. Before the onset of generalized
weakness
ing, or meals. She denied having a history of tobacco, cannabis, or other
recreational drug use. She is a retired teacher by profession who lives in
her home with her husband of 45 years.
the fractur
ideations, intent, or plan. There were no reports of any perceptual disturbances or delusions. Her St. Louis University Mental Status (SLUMS)
examination score was 27. The dose of medications was confirmed by
checking the pill bottles her husband brought in. A check of the prescription drug monitoring system confirmed that she had been refilling
her gabapentin and clonazepam regularly, on time, and not earlier than
prescribed.
electrolytes, thyroid stimulating hormone, vitamin B
folate levels were normal. However, her renal function test demonstrated decreased glomerular filtration rate (28 mL/min/1.73m
elevated creatinine levels (3.2 mg/dL), which were new findings after
normal kidney function results 2 months previously.
reduction and internal fixation. Ms. McGraw’s postoperative pain was
managed with oral oxycodone for 5 mg every 6 hours for 3 days, gradually tapered, and stopped. Oral acetaminophen 500 mg was then provided every 6 hours as needed for pain. Her impaired renal function
was considered due to ibuprofen-induced acute kidney injury (AKI)
and was managed conservatively during hospital stay with hydration
and avoidance of nonsteroidal anti-inflammatory drugs. Oral gabapen-
, she did not need assistance with bathing, dressing, groom-
Physical examination did not reveal any significant findings besides
e on her right wrist. She did not endorse suicidal or homicidal
Laboratory results of complete blood count, hepatic function test,
, vitamin B12, and
1
2
) and
The fracture was surgically treated during hospitalization with open
Safe Prescribing Practices for Older Adults 97
tin was held in case the ataxia and generalized weakness were caused
by possible elevated gabapentin levels resulting from decreased renal
excretion of gabapentin after the AKI.
Her home medications of clonazepam, escitalopram, and doxepin
continued for the hospital stay. During discharge planning, there
were
was concern that polypharmacy might have also been a cause of her fall.
Ms. McGraw’s medical team worried that her high doses of clonazepam
and doxepin might have contributed to generalized weakness and
ataxia along with the gabapentin and alcohol use. When these concerns
were discussed with her, she was very reluctant to change medications.
She claimed that they had kept her stable for many years and worried
that alternative medications for her peripheral neuropathy, depression,
and anxiety might not be as effective.
When Ms. McGraw was educated about the potential problems that
can be caused by the anticholiner
effects of gabapentin and clonazepam on cognition and ataxia, she
agreed to discuss her medications. Ms. McGraw was willing to discuss
changing her medications for anxiety and depression first, as she has not
tried other alternative medications for many years. She agreed to stop
drinking wine. She requested referral to an outpatient psychiatrist and
wanted to continue the same dose of her home medications of clonazepam, doxepin, and escitalopram. She was more concerned about her
neuropathic pain and wanted to continue oral gabapentin. She agreed to
decrease the dose of oral gabapentin to 200 mg three times a day when
her renal function became normal. She was also referred to a neurologist
for management of her migraines and peripheral neuropathy.
After her discharge, Ms. McGraw established care with an outpatient psychiatrist. She had stopped consuming any alcohol, and a gradual taper of clonazepam was planned to help her slowly adapt, with
provided time to le
ication changes were made. Oral clonazepam was decreased to 1 mg in
the morning and 2 mg at night, with a plan to decrease it again to 1 mg
twice daily after 2–3 months. Oral escitalopram was increased to 15 mg
daily to better manage her anxiety, and oral doxepin was planned to be
decreased in future visits. Ms. McGraw was also referred to a psychologist for cognitive-behavioral therapy for anxiety.
arn new coping skills while other psychotropic med-
gic side effects of doxepin and the side
While the focus of this section has been on psychotropic medica-
tions, we note that safety concerns can arise with many other medication categories, including anticholinergic medications for urinary
incontinence, nonster
oidal anti-inflammatory drugs, proton-pump inhibitors, and skeletal muscle relaxants. We refer the reader to the previously mentioned Beers criteria for more details on safety concerns with
nonpsychotropic medications in older adults.
Next, we briefly discuss safely addressing anxiety, insomnia, and
, symptoms that often lead to prescription of potentially inappro-
pain
priate medications to older adults.
98 Substance Use in Older Adults
Safely Addressing Anxiety and Insomnia in
Older Adults
Older adults are often prescribed sedatives, hypnotics, or anxiolytics for
the treatment of anxiety and insomnia. Older adults are also frequent
users of OTC hypnotics such as diphenhydramine. We strongly encourage clinicians to educate patients about safety concerns associated with
OTC hypnotics. Although full discussion of the treatment of anxiety
disorder and insomnia in older adults is beyond the scope of this chap-
ment of anxiety and insomnia, including psychotherapy, rather than
benzodiazepines and other sedative
Benzodiazepines may be considered for older adults with severe
anxiety disor
ever, we note that in the last 30 years, there has been no randomized
lled trial in support of their use (Béland et al. 2011). Before initi-
contro
ating a benzodiazepine, the clinician should carefully weigh risks and
benefits and should check for possible drug–drug interactions. Avoid
benzodiazepines in frail individuals or patients already taking opioid
medications. Long-acting benzodiazepines in older adults should be
avoided for most indications because of lower efficacy and higher risk
of harm. Ask patients to monitor for and immediately report side effects, especially falls and cognitive impairment.
Short-term use of z-drugs may be considered for older adults whose
insomnia has not responded to sleep hygiene and cognitive-behavioral
therapy and whose sleep comorbidities (e.g., REM sleep behavior disorder and obstructive sleep apnea) have been adequately addressed.
Clinicians should remember that z-drugs are not safer or more efficacious than benzodiazepines and are approved only for the short-term
management of insomnia—we re
close monitoring for side effects.
ders that have not responded to other treatments. How-
s or hypnotics.
commend fewer than 30 days, with
Safely Addressing Pain in Older Adults
A detailed discussion of the treatment of pain in older adults is beyond the
scope of this book. However, we briefly cover it here, given how opioids
are inappropriately prescribed to older adults. The treatment of pain
should involve a multidisciplinary approach, including primary care,
psychiatry, and psychology. Clinicians should explore non-opioid treatment options such as acetaminophen, topical agents (lidocaine, capsaicin),
selective noradr
tiepileptic medications (gabapentin, pregabalin), nonsteroidal anti-in-
energic reuptake inhibitors (duloxetine, venlafaxine), an-
Safe Prescribing Practices for Older Adults 99
flammatory drugs (NSAIDs), physical therapy, occupational therapy,
complementary therapies (acupuncture, transcutaneous electrical nerve
stimulation), and psychotherapeutic interventions (cognitive-behavioral
therapy, group therapy, biofeedback). Note, though, that there may be
concerns even with these alternate medications, for example, NSAIDs can
cause gastrointestinal bleeding or renal dysfunction, and antiepileptic
drugs can lead to sedation, cognitive impairment, or falls.
Opioids can be appropriate for short-term use for acute pain. For
chronic pain, such as noncancer pain, non-opioid pain medications or
nonpharmacological pain management options can be appropriate, effective, and well tolerated (Dowell et al. 2016; Gatchel et al. 2014). CDC
opioid prescription guidelines (Dowell et al. 2016) recommend that clinicians use precautions to reduce risks (e.g., recommending naloxone,
which is now available OTC, to
forming functional assessment at appropriate intervals, setting goals
for treatm
scription drug monitoring program before providing prescriptions.
Dosing of opioids in
starting dose in younger adults, with greater intervals between doses
(Naples et al. 2016).
ent, maintaining frequent follow-ups, and reviewing the pre-
older adults should start at only 25%–50% of the
reverse overdose) and encourage per-
Risk of Misuse or Dependence
Most misused medications—pain relievers, stimulants, sedatives, hypnotics, and anxiolytics—are obtained by prescription (Colliver et al.
2006). Ol
somnia, chronic pain, or anxiety and subsequently develop substance
use disord
topic in greater detail in chapters 7, 8, and 9.
with great caution, since there is a real risk that they may be abused or
misused (Ates Bulut and Isik 2022; Schifano et al. 2021):
• Opioid analgesics: oxycodone, hydrocodone, morphine, codeine, fen-
• Benzodiazepines: lorazepam, diazepam, alprazolam, triazolam,
• Stimulants: amphetamine salts, methylphenidate
• Barbiturates: phenobarbital, pentobarbital
• Gabapentinoids: gabapentin, pregabalin
• Z-drugs: zolpidem, zaleplon, eszopiclone
• Antidepressants: venlafaxine, bupropion
der adults may misuse medications prescribed to address in-
ers (Aira et al. 2008; Levi-Minzi et al. 2013). We cover this
We recommend avoiding the following medications or using them
tanyl, meperidine, methadone, hydromorphone, and oxymorphone
clonazepam, a
nd chlordiazepoxide
100 Substance Use in Older Adults
• Antipsychotics: quetiapine
• Dopaminergic medications: levodopa
• OTC medications: dextromethorphan, loperamide, diphenhydramine
SAFETY CONCERNS WITH PSYCHOTROPIC
MEDICATIONS, INCLUDING DRUG–DRUG
INTERACTIONS
Opioids
Opioid prescriptions in older adults have increased fourfold in the past
decade with no significant improvement in prevailing pain or disability
(Rummans et al. 2018; Sites et al. 2014). According to the Centers for
Disease Control and Prevention (2022), 75% of the nearly 92,000 drug
overdose deaths in the United States in 2020 involved an opioid. Synthetic opioids are the primary driver of opioid-related overdose deaths
(82.3%).
According to the Agency for Healthcare Research and Quality
(2019
), opioid pain relievers are one of four medication types that cause
half of emergency department visits for adverse medication side effects
in Medicare recipients; the others are antidiabetic agents, oral anticoagulants, and antiplatelet agents. The number of adults visiting the emergency department because of prescription opioid tramadol increased
1% from 2005 to 2011 (Bush 2013).
by 48
The most common opioids prescribed are hydromorphone, oxyco-
done
, codeine, methadone, fentanyl, meperidine, hydrocodone, and
morphine. Morphine and other opioid medications are metabolized by
the liver before being excreted by the kidneys. Metabolism of most opioid drugs is relatively rapid, and their duration of action is 4–6 hours on
average, although one of the mos
cations, methadone, has the longest half-life at 36 hours. All major
opioid medications
enzymes, particularly CYP3A4 and CYP2D6. Therefore, medications
that induce or inhibit the production of CYP450 isoenzymes can result
in significant drug–drug interactions when combined with opioid
drugs (see Table 4–2). Oxycodone and hydromorphone are less likely
than other opioids to interact
Opioids that should be avoided or used with extreme caution are
meperi
dine and tramadol. They increase the risk for serotonin syn-
are metabolized by cytochrome P450 (CYP450) iso-
t commonly prescribed opioid medi-
with other drugs (Naples et al. 2016).
Safe Prescribing Practices for Older Adults 101
Table 4–2. Commonly prescribed psychotropic medications that have
drug–drug interactions with opioids
CYP3A4 CYP2D6
Inducer Inhibitor Inducer Inhibitor
Buprenorphine Benzodiazepines None Bupropion
Modafinil Alprazolam Haloperidol
Carbamazepine Midazolam Citalopram
Ziprasidone Diazepam Escitalopram
Oxcarbazepine Nefazodone Paroxetine
St. John’s wort Fluvoxamine Chlorpromazine
Nicotine Fluoxetine
Methadone Duloxetine
Oxycodone Codeine
Fentanyl Methadone
Morphine
Source. English et al. 2012; Lynch and Price 2007; Mandrioli et al. 2010.
drome when used along with serotonergic antidepressant medications,
especially in the setting of poor hepatic and renal function (Cheatle and
Savage 2012).
Morphine should be avoided in people with renal impairment, be-
cause the significantly decreased excretion of metabolite morphine-6-
ucuronide increases the risk of seizures and other medical complica-
gl
tions. Fentanyl and methadone are considered safer in renal failure (Gelot and Nakhla
2014). Similarly, compromised liver function can cause
sedation, encephalopathy, and constipation when opioid dosages are
not adjusted appropriately.
Buprenorphine
The World Health Organization (WHO) (2023) has listed buprenorphine
as an “essential medication” (Herget 2005). Certain buprenorphine formulations are approved to treat chronic pain, such as buprenorphine
transd
ermal system; more commonly, buprenorphine is used for opioid
withdrawal or long-term maintenance treatment for opioid use disorder
(Karp et al. 2014). Compared with methadone, data on the efficacy of buprenorphine in older adults are limited, but it still may be preferable be-
102 Substance Use in Older Adults
cause of the lower risk of QTc prolongation, erectile dysfunction, and
withdrawal symptoms (Joshi et al. 2019). In a short-term study on the use
of low-dose buprenorphine in older adults with depression, the medication was found to be safe and well tolerated (Herget 2005). Buprenorphine does not typically require dose adjustment in renal failure, but
there are reports of respiratory and neurologic complications in older
hospitalized patients (Macintyre and Huxtable 2017).
Methadone
Methadone is available through federally certified and accredited opioid treatment programs and is a well-known medication to prevent opioid withdrawal symptoms and reduce cravings (Substance Abuse and
Mental
done, like buprenorphine, an essential drug. Methadone can be used to
treat chr
tion, which can cause a potentially deadly cardiac arrhythmia (World
Health Organization 2023).
and inhibito
half-life and a high risk of QTc prolongation but may be considered safe
in renal failure (Pergolizzi et al. 2008). Given these safety concerns, it is
best prescribed and monitored by a clinician who is experienced in
managing methadone.
Health Services Administration 2020). WHO considers metha-
onic pain in older adults, but it carries a risk of QTc prolonga-
As noted in Table 4–2, methadone may interact with both inducers
rs of cytochrome P450 enzymes. Methadone has a long
Benzodiazepines
Benzodiazepines are prescribed to treat anxiety disorder and insomnia
in older adults. Despite the risk of falls, fractures, confusion, motor vehicle accidents, and overdose, benzodiazepines are often prescribed
long term
al. 2011; Jones et al. 2013; Maust et al. 2016; Tannenbaum et al. 2014).
Moreover, there is growing concern that benzodiazepines may reduce
the benefit of psychotherapeutic interventions in anxiety disorders and
PTSD (Otto et al. 1996; Rothbaum et al. 2014). Additionally, there is limited evidence to support the use of benzodiazepines in managing behavioral symptoms of dementia, except for intramuscular lorazepam
(Meehan et al. 2002), which
bition, confusion, and worsening agitation (Wiechers et al. 2013). In a
study of a private insurance claims database, nearly half of the patients
who received a benzodiazepine did not have a diagnosis of a mental
health disorder or significant psychiatric symptoms to justify its use
(Wiechers et al. 2013).
without a clear need for ongoing treatment (Dassanayake et
might instead increase paradoxical disinhi-
Safe Prescribing Practices for Older Adults 103
The benzodiazepines most commonly prescribed to older adults are
lorazepam, clonazepam, diazepam, and alprazolam. Opioids are the
most commonly coprescribed controlled medications associated with
overdose; 31% of opioid poisoning deaths also involved a benzodiazepine (Chen et al. 2014); see next section. CYP3A4 mainly catalyzes the
metabolism of the benzodiazepines, except for lorazepam, oxazepam,
and temazepam. Therefore, antidepressants such as fluoxetine and paroxetine inhibit the metabolism of alprazolam, midazolam, and diazepam via CYP3A4. The combined use of fluoxetine and alprazolam
increases the concentration of alprazolam by 30%. Fluvoxamine, a potent inhibitor of CYP1A2, can also inhibit the metabolism of alprazolam
and incr
(Fleishaker and Hulst 1994). Sertraline and citalopram are less likely to
have an inhibitory effect. A few widely used medications, such as cimetidine, increase the concentration and prolong the half-life of alprazolam and triazolam (Pourbaix et al. 1985); conversely, omeprazole
reduces the clearance of intravenous diazepam by 27% and increases
the half-life by 36% (Fleishaker and Hulst 1994). Valproic acid increases
the plasma concentration of lorazepam by impairing glucuronidation
(Samara et al. 1997), and carbamazepine reduces the level of alprazolam
as an inducer (Arana et al. 1988) (see Table 4–2). Similarly, CYP3A4 inhibitors such as grapefruit juice, macrolide antibiotics, and antifungals
(k
ease the half-life of alprazolam from 20 hours to 34 hours
etoconazole, itraconazole) can increase benzodiazepine levels.
Coprescription of Benzodiazepines and
Opioids
Coprescribing benzodiazepines and opioids is common in clinical
settings and poses significant morbidity and mortality risks in older
adults. Concomitant use of a benzodiazepine and opioids increases
the risk of overdose death up to fourfold compared with prescription
of opioids alone (Sun et al. 2017).
Combination of benzodiazepines and opioids is associated with a
higher risk of accidental overdose, heightening the risk of medical comorbidities such as obesity, hypoventilation, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and encephalopathy
(Dowell et al. 2016). In light of these concerns, the FDA has issued a
black box warning for potential respiratory suppression and death
caused by coprescribing opioids with other central nervous system
(CNS) depressants, including benzodiazepines (U.S. Food and Drug
Administration 2016).
104 Substance Use in Older Adults
If these medications are used together, the FDA has recommended
limiting the dosages and duration while achieving the desired clinical
effect. As older adults risk experiencing negative effects from opioid
and benzodiazepine medications, clinicians should take even greater
caution in this population.
The FDA has advised against withholding buprenorphine or methadone treatment for opioid use disorder from patients taking benzodiazepines or oth
and CNS depressants must be carefully monitored, but the harm caused
by untreated opioid use disorder may outweigh the risks of this combination (U.S. Food and Drug Administration 2017).
er CNS depressants. Patients who take both buprenorphine
Z-Drugs
Z-drugs (zolpidem, zaleplon, and eszopiclone) have a relatively rapid
onset and short duration of hypnotic action in comparison to benzodiazepines. The half-life of z-drugs ranges from 1 to 5 hours. Z-drugs are
mainly metabolized by CYP3A4 and should not be used concurrently
with drugs that inhibit CYP3A4, such as clarithromycin, erythromycin,
and ketoconazole. The harmful effects of z-drugs are similar to those of
benzodiazepines.
Cannabis
In the past few years, cannabis has been legalized for recreational and
medical use in several American states, although it is still illegal at the
federal level. In older adults, the prevalence of cannabis use in the past
year increased from 2.4% in 2015 to 4.2% in 2018 (Han and Palamar
2020). There is a lack of data regarding interactions of cannabis with
specific medications; however, cannabis itself can worsen memory,
thought process, depression, and anxiety (Bolla et al. 2002; Briscoe and
Casarett 2018). Please refer to Chapter 10 for a detailed discussion of the
cannabis by older adults.
use of
Over-the-Counter Medications and
Dietary Supplements
Herbal products and OTC medications are used for a wide range of reported benefits such as improving concentration, memory, and cognitive dysfunction and for antihypertensive and antilipidemic effects.
Older a
teractions of OTC medications and herbal/nutritional supplements
dults may not be aware of the adverse effects and negative in-
Safe Prescribing Practices for Older Adults 105
with prescription medications. According to national survey data,
nearly 38% of older adults take at least one OTC medication, and >63%
take a dietary supplement (Qato et al. 2016). Between 2005 and 2011, the
use of OTC medications declined from 44.4% to 37.9%, but the use of dietary supplements increased from 51.8% to 63.7% in older adults in the
United States (Qato et al. 2016). Approximately 15.1% of older adults
were found to be at risk for a potential major drug–drug interaction in
2010–2011 compared with 8.4% in 2005–2006 (Qato et al. 2016).
Gingko biloba, garlic, ginseng, aloe vera, chamomile, spearmint,
and ginger are commonly used by older
Souza Silva et al. 2014). Among these herbal medicines, gingko and garlic are most commonly used by community-dwelling older adults, and
both of these supplements interact with anticoagulants and OTC pain
medications (naproxen, diclofenac sodium), increasing the risk of
bleeding and bruises (Borrelli et al. 2007; Herrmann et al. 2022). Gingko
is well known for its interactions with thiazide diuretics; garlic, niacin,
and omega-3 fatty acid can increase the risk of bleeding (Chen et al.
2011). Despite a fourfold increase in the use of omega-3 fatty acid in
older adults in 2011 (Qato et al. 2016), no strong evidence has been
found that it lowers risk of all-cause mortality, cardiac death, sudden
death, myocardial infarction, or stroke (Rizos et al. 2012). Multiple
herb–drug interactions have been identified with St. John’s wort and
ginseng. Ginseng reduces blood levels of warfarin and may induce mania if taken concomitantly with phenelzine. St. John’s wort reduces
blood concentrations of warfarin, digoxin, indinavir, theophylline, cyclosporine, tacrolimus, amitriptyline, and midazolam; it also increases
risk of serotonin syndrome if used along with serotonergic agents, since
it is a monoamine oxidase inhibitor (Chen et al. 2011; Nicolussi et al.
2020).
adults in the United States (de
ADDRESSING POLYPHARMACY
Polypharmacy increases expenditure, the risk of side effects, frequency
of hospital admissions, and noncompliance and decreases quality of
life. The majority of older adults in the United States take at least one
prescription medication—according to National Center for Health Statistics (2019) data, in 2018, 87.5% of older adults had at least one prescribed medication, and 39.8% were taking five or more prescription
cations at the same time.
medi
This increase in use of medications by patients is known as polyphar-
macy,
which is traditionally defined as the concomitant use of five or
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