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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5538_Библиотеки_им_академика_М_И_Перельмана
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256 Substance Use in Older Adults
significant results in head-to-head comparisons, being superior to CBT
(OR 2.44, 95% CI 0.02–5.88, P =0.045), noncontingent rewards (OR 3.31,
95% CI 1
wards (OR 4.07, 95% CI 1.13–14.69, P=0.031). The combination of
re
community re
ficacious than CBT alone, contingency management alone, contingency
management plus CBT, or 12-step program plus noncontingent rewards
(ORs 2.50 [P=0.039] to 5.22 [P< 0.001]).
comes in those using stimulants, contingency-based approaches seem
to be mos
remains a concern for many seeking treatment. More research exploring
the implementation and viability of such approaches in community
care settings is warranted. For those with cognitive impairment, therapy would be challenging and potentially less beneficial. Depending on
the level of cogni
with cognitive impairment in activities of daily function can help with
the amount of use (e.g., decreasing the availability of substance or providing distractions).
.32–8.28, P =0.010), and 12-step program plus noncontingent
inforcement with contingency management was more ef-
Although multiple psychosocial treatment options improve out-
t successful. Limited access to contingency-based programs
tive impairment, involving those who assist patients
Pharmacological Interventions for
Methamphetamine Use Disorder
There are no FDA-approved medications for MUD, but studies have
been conducted in several classes of medications. Unfortunately, small
sample sizes and differences in clinical design and outcomes have limited the interpretation of these studies and conclusions reached with
systematic reviews, and more research is needed in this field. Clinicians
should be aware of the existing evidence for treatment, however, which
is summarized in this section by medication class. The literature on
pharmacotherapy treatments is sparse and mostly conducted in a
younger population. There are no specific treatment trials for older
adults, and the evidence we summarize here is extrapolated from the
general adult population.
Antidepressants
One systematic review (Bhatt et al. 2016) and three trials (Colfax et al.
2011; Elkashef et al. 2008; Shoptaw et al. 2006) examining antidepressants found no difference between antidepressants and placebo in abstinence, retention, or adverse effects. Specifically, an RCT comparing
placebo to sertraline with and without continency management found
Stimulant Use Disorder in Older Adults 257
that those receiving sertraline were less likely to remain in and or
achieve abstinence (Shoptaw et al. 2006). A small trial (N = 60) comparing mirtazapine to placebo in men who have sex with men found that
those r
et al. 2011), but further studies are needed. The systematic review and
one RCT (Elkashef et al. 2008) found that bupropion was not different
from placebo in outcomes.
eceiving mirtazapine had more negative urine analyses (Colfax
Antipsychotics
Two RCTs compared aripiprazole to placebo and found no difference in
sustained abstinence, use, retention, or harms (Coffin et al. 2013; Tiihonen et al. 2007).
Psychostimulants
A systematic review of 11 RCTs examining three psychostimulants (dexamphetamine, modafinil, methylphenidate) provided low-strength evidence that psychostimulants provide no benefit over placebo across
tcomes (sustained abstinence, use, retention, adverse effects).
all ou
Modafinil or dexamphetamine were not superior to placebo in any
outcome; methylphenidate had low-strength evidence of less methamphetamine use (Bhatt et al. 2016). Given the varying quality and
hetero
geneity of the trials, these results need further investigation.
Muscle Relaxants and Anticonvulsants
One RCT (N = 140) found lower methamphetamine use in patients
treated with topiramate versus placebo (Elkashef et al. 2012), but this result should be interpreted with caution given lack of replication. A
all trial (N=88) compared baclofen, gabapentin, and placebo and
sm
found no dif
phetamine use disorder (Heinzerling et al. 2006).
ference in outcomes related to methamphetamine/am-
Naltrexone
Four studies on naltrexone had varying trial parameters and showed
mixed results. One United States–based trial (N=100) studying men
who have sex with men given naltr
found no difference in use or retention (Coffin et al. 2018). An Icelandic
trial (Runarsdottir et al. 2017) compared patients transitioning from inpatient to outpatient who received naltrexone injections or placebo and
exone and behavioral interventions
258 Substance Use in Older Adults
found no difference in outcomes. A Swedish trial in newly abstinent patients found that patients with naltrexone had a higher percentage of
negati
ve UDS results (Jayaram-Lindström et al. 2008). A Russian trial
studying patients with comorbid amphetamine and opioid dependence
found a nonsignificant trend favoring naltrexone for negative UDS results (Tiihonen et al. 2012).
Combining Medications
A recent multisite placebo-controlled trial (N=403) evaluated combining extended-release injectable high-dose naltrexone plus an oral maximum dose of bupropion for the treatment of MUD (Trivedi et al. 2021).
Patients r
who did not respond were randomly assigned to receive either the
treatment or placebo for the next 6 weeks. The overall response for the
trial was low, but there was a significant difference in response between
the treatment arm (13.6%) and the placebo arm (2.5%).
eceived the treatment arm or placebo for 6 weeks, and those
Pharmacological Interventions for Cocaine Use
Disorder
Although there has been more research than for MUD, no medications
have been approved to treat cocaine use disorder. The existing evidence
is summarized in this section by medication class. No studies specifically examined older adults, and the available evidence is mainly from
a general adult population.
Antidepressants
The most comprehensive systematic review of 37 trials (N =3,551) covering two major classes (tricyclics and SSRIs) as well as bupropion, nefazodone,
class of pharmacotherapy was not more effective than placebo in cocaine use disorder. No significant differences were found for continuous abstinence, dropout rates, or safety. Average number of weeks in
treatment slightly fa
report scores. New RCTs have been published since then, and one additional systematic review has been published on bupropion.
Sertraline. Recently abstinent patients remained abstinent longer on
se
rtraline than placebo while receiving CBT (Oliveto et al. 2012). Another trial, which compared sertraline and combined sertraline and gabapentin with placebo in r
receiving CBT and contingency management, found that relapse rates
and venlafaxine was published in 2011 (Pani et al. 2011). This
vored antidepressants, as well as depression self-
ecently abstinent patients concurrently
Stimulant Use Disorder in Older Adults 259
were lower in the sertraline group, but not in the sertraline and gabapentin group (Mancino et al. 2014). Retention rates did not differ. For unknown reasons, other SSRIs have not shown a similar level of efficacy.
Venlafaxine. An RCT of patients with comorbid depression showed
that the
placebo (Raby et al. 2014).
Mirtazapine. In a small RCT of patients with comorbid depression, pa-
tients did not differ in cocaine consumption with mirtazapine versus
plac
Bupropion. Evidence regarding bupropion is mixed. A systematic re-
view covering three trials found superiority of bupropion over placebo
for abstinence and
2019). In contrast, one of the largest multisite, placebo-controlled RCTs
evaluating methadone-maintained individuals with co-occurring cocaine dependence found no difference in use, depression, or psychosocial functioning for those treated with bupropion versus placebo
(Margolin et al. 199
re was no difference in relapse or use between venlafaxine and
ebo (Afshar et al. 2012).
no difference in overall cocaine use (Chan et al.
5).
Dopamine Agonists
A 2015 systematic review of 24 trials found no differences between any
dopamine agonist (amantadine, bromocriptine,
golide, cabergoline, hydergine, pramipexole) and placebo on retention,
abstinence, or adverse events (Minozzi et al. 2015a).
L-dopa/carbidopa, per-
Antipsychotics
A systematic review of 14 RCTs studying seven medications (risperidone, olanzapine, quetiapine, lamotrigine, aripiprazole, haloperidol,
and reserpine) showed no difference of antipsychotics over placebo in
terms of cocaine use, cravings, adverse events, side effects, or improved
treatment retention (Indave et al. 2016). An RCT of aripiprazole versus
placebo given to methadone-maintained patients with comorbid cocaine use disorder that also received contingency management and
achieved abstinence within 12 weeks had similar results in abstinence,
time to relapse, retention, and harm (Moran et al. 2017).
Psychostimulants
A 2016 Cochrane Review included 26 trials (N= 2,366) and examined
nine medications (modafinil, mazindol, methylphenidate, dexamphetamine, lisdexamfetamine, methamphetamine, mixed amphetamine
260 Substance Use in Older Adults
salts, selegiline, and bupropion, which we covered earlier in “Antidepressants”) (Castells et al. 2016). Overall, psychostimulants were well
tolerated
had improved sustained abstinence, which was defined as 3 weeks of
nonuse, but the mean days of use and treatment retention did not differ.
Subanalyses showed that methadone-maintained patients with comorbid opioid use disorder and cocaine use disorder, and those without comorbid ADHD, benefited the most. Subsequent studies suggested that
patients with comorbid alcohol use disorder and cocaine use disorder
might need higher doses of psychostimulants. The most promising
medications in the study were dexamphetamine, mixed amphetamine
salts, and bupropion. The authors concluded that further research is
warranted owing to the low quality of the studies included. Mazindol
was underpowered in the studies, and no significant difference was
found. No difference was found regarding methylphenidate, methamphetamine, lisdexamfetamine, selegiline, or modafinil for outcomes.
Dexamphetamine. A few additional studies on psychostimulants have
been con
dexamphetamine in treatment-refractory heroin- and cocaine-dependent
individuals found that dexamphetamine resulted in fewer days of cocaine use compared with placebo (Nuijten et al. 2016).
and did not have serious adverse effects. Experimental groups
ducted since the 2016 Cochrane Review. One RCT using oral
Mixed Amphetamine Salts. A large study showed that mixed amphetamine salts resulted in better sustained abstinence than placebo in patients with comorbid ADHD and cocaine use disorder (Levin et al. 2015)
and that abstinence likely pr
al. 2018).
Modafinil. Studies on modafinil have mixed results. A meta-analysis
studies (N=896) comparing modafinil with placebo found that
of 11
modafi
rates (this was influenced by one negative study) (Sangroula et al. 2017).
The meta-analysis found that modafinil was superior in terms of fewer
days of cocaine use, and a subgroup analysis of United States–based
studies showed that it improved abstinence rates.
nil was well tolerated but did not benefit retention or abstinence
eceded improvements in ADHD (Levin et
Anticonvulsants and Muscle Relaxants
One systematic review (20 RCTs; N =2,068) of anticonvulsant drugs examined carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine,
topiramate,
ences in retention for any anticonvulsant pharmacotherapy except for
ga
bapentin (favoring placebo) and vigabatrin (favoring treatment but
and vigabatrin (Minozzi et al. 2015b). There were no differ-
Stimulant Use Disorder in Older Adults 261
not reaching statistical difference). No differences were found in terms
of cocaine use, craving, severity of substance use, depression, anxiety,
or treatment retention.
Topiramate. Additional studies since that review was published add to
the evidence of treatment options. One small RC
mate significantly improved abstinence and retention (Baldaçara et al.
2016). A meta-analysis of five studies (N= 518) on topiramate found that
y increase continuous abstinence (Singh et al. 2016). An RCT on
it ma
topiramate in treatment of crack cocaine dependence found that topiramate reduced the quantity and frequency of use and the money spent
on cocaine in the first 4 weeks but was equal to placebo by 12 weeks
(Baldaçara et al. 2016).
Vigabatrin. Two RCTs on vigabatrin have been published and found
no differences in outcomes (Oliveto et al. 2011; Somoza et al. 2013).
Baclofen. The only muscle relaxant examined so far was baclofen, which
had no ef
2012; Kahn et al. 2009).
fect on any outcomes compared with placebo (Kablinger et al.
T found that topira-
Cognitive-Enhancing Drugs
Two small RCTs examined memantine and atomoxetine, with contingency management, versus placebo and found no significant difference
in outc
omes (Bisaga et al. 2010; Walsh et al. 2013).
Anxiolytics
One small, multisite RCT compared buspirone to placebo, placebo plus
contingency management, and once-weekly optional individual or
group psychosocial treatment and found no difference in outcomes
(Winhusen et al. 2014).
Pharmacotherapies in Other Substance Use Disorders
Disulfiram. A 2010 systematic review of seven studies on disulfiram
(N=492) for cocaine use disorder found trends favoring disulfiram that
did not re
owing to different outcomes. Other studies found no difference between disulfiram and placebo in terms of abstinence (Carroll et al. 2016;
Schottenfeld et al. 2014) or use (Carroll et al. 2012, 2016; Kosten et al.
2013; Oliveto et al. 2011), but significant difference in retention, with
those receiving disulfiram less likely to be in treatment and having
more side effects, namely elevated liver enzymes and rash.
ach significance (Pani et al. 2010). Studies could not be pooled
262 Substance Use in Older Adults
Acamprosate. One study found no difference between acamprosate
and placebo (Kampman et al. 2011).
Naltrexone. Most studies of naltrexone in cocaine use disorder involved patients with comorbid alcohol use disorder. Several studies
found no dif
Pettinati et al. 2008, 2014; Schmitz et al. 2009). One study of naltrexone
and behavioral intervention on patients with comorbid cocaine use disorder and alcohol use disorder found no difference in cocaine use, and
odds of a heavy drinking
Varenicline. One study found cocaine use to be lower with varenicline,
but the
2012); another conducted in opioid-dependent patients did not find differences in use or retention (Poling et al. 2010).
ference between naltrexone and placebo (Hersh et al. 1998;
day were reduced (Schmitz et al. 2009).
difference did not reach statistical significance (Plebani et al.
Opiate Agonists
Two RCTs compared methadone to buprenorphine in comorbid cocaine
and opioid use, and found, with insufficient strength of evidence, longer abstinence and better retention with methadone (Schottenfeld et al.
1997,
2005). Similarly, an RCT found that 16 mg of buprenorphine (but
not 4 mg) and naloxone resulted in less use than placebo, but with insufficient strength of evidence and no difference in abstinence and retention rates (Ling et al. 2016).
Research around pharmacological treatment for cocaine use disorder has not shown strong evidence for any one therapy to be applied
consistently for
FDA. There are promising results, but much more research should be
done before any pharmacotherapy becomes the standard of care. Familiarity with the available evidence, however, can help clinicians weigh
benefits
evidence for treatment of stimulant use disorders remains psychotherapy treatments.
and risks in treating each individual patient. Currently, the best
clinical use. No pharmacotherapies are approved by the
Other Approaches
There are promising lines of investigation for the nonpsychosocial treatment of stimulant use disorders, but none have been approved by the
TA-CD, an active cocaine vaccine, stimulates antibodies that bind
FDA.
to cocaine and prevent it from crossing the blood–brain barrier. It has
shown positive results in animal models but mixed results in clinical trials. One trial of methadone-maintained patients with comorbid cocaine
use di
sorder had greater abstinence from cocaine in those who had
Stimulant Use Disorder in Older Adults 263
higher IgG antibody levels (Martell et al. 2009). A Phase III clinical trial
in humans showed no difference between TA-CD and placebo regardless of IgG antibody levels (Kosten et al. 2014). TA-CD is being studied
in huma
well-defined complementary/alternative medicine approaches for
stimulant use disorder.
ns but so far has not proven to be clinically useful. There are no
SUMMARY
The rate of stimulant use disorders (namely, methamphetamine and
cocaine) has rapidly increased in the past two decades, and these disorders are associated with serious mental and physical comorbidities.
Clinicians
use and of withdrawal syndromes for proper management. General
screening tools for substance use can be applied to stimulant misuse,
but the diagnosis is made based on DSM criteria. Although there are
no FDA-approved medications for stimulant use disorders, psychosocial interventions have been shown to be effective and are considered
the st
older adults with stimulant use disorder, and much of what we know is
extrapolated from the general adult population. Clinicians should not
assume older adults are less likely to change or benefit from treatment.
In taking care of older adults, providers should consider cognitive and
physical impairments, independence in activities of daily living, and
family involvement.
should be aware of the presentations of acute and chronic
andard of care. There are no specific guidelines or evidence for
KEY POINTS
• Methamphetamine and cocaine use disorders constitute the majority of stimulant use disorders. Methamphetamines are synthetic
drugs
and are the fastest growing drug of misuse worldwide. Cocaine is a natural substance extracted from the coca plant and exists in two forms: cocaine salt (cocaine HCl), a water-soluble
powder that is used in injections; and cocaine base (“crack”), a
water-insoluble rock that is often smoked and is preferred by older
adults.
• Excessive methamphetamine use can lead to death through myocardial infarction, stroke, hypertensive crisis, or hyperpyretic
crisis.
• Regular methamphetamine use leads to poor cognition, poor dentition, psychiatric conditions, sexually transmitted diseases, and
264 Substance Use in Older Adults
cardiovascular pathology. Users who develop psychosis are clinically indistinguishable from those with paranoid schizophrenia.
• Excessive acute use of cocaine can lead to coronary adverse
events, stroke, ar
nary toxicity, and tactile hallucinations. Most cocaine users use low
amounts in low frequencies.
• Long-term cocaine use is associated with increased psychiatric
nditions, decreased libido, male impotence, gastric ulcers, car-
co
diopulmonary dysfunction, and cognitive impairment.
• Stimulant withdrawal is marked by sedation, hyperphagia, dysphoria, and crav
during this time.
• Cocaine supplies can be adulterated by levamisole, which causes
agranulocytosis and vasculiti
amine supplies are increasingly adulterated with fentanyl, which
leads to respiratory depression and has been a driver of deaths
among stimulant users.
• The diagnosis of stimulant use disorder is made using DSM criteria. Urine drug screens are specific for cocaine; methamphetamines are prone to false positives.
• Psychosocial treatment, particularly contingency management,
en shown to be effective and is the standard of care for stim-
has be
ulant use disorders.
• There are no FDA-approved medications for either methamphetamine or cocaine use disorder.
rythmias, headache, hyperthermia, acute pulmo-
ing of substance. Increased suicidality occurs
s. Both cocaine and methamphet-
RESOURCES FOR PATIENTS, FAMILIES,
AND CAREGIVERS
Substance Abuse and Mental Health Services
Administration
The Substance Abuse and Mental Health Services Administration
(SAMHSA) (www.samhsa.gov) is the agency within the U.S. Department of Health and Human Services that leads public health
to advance the behavioral health of the nation. SAMHSA
efforts
has educational resources on stimulant use disorder, resources for
families coping with mental illness or substance use, information
on how to find treatment, and treatment locators.
Stimulant Use Disorder in Older Adults 265
National Helpline: Free 24/7 treatment referral and information ser-
vice available in English and Spanish: 1-800-662-HELP (4357)
24/7 Suicide and Crisis Lifeline:
Call or text 988
National Alliance on Mental Illness
The National Alliance on Mental Illness (NAMI; www.nami.org/
home) is the nation’s largest grassroots mental health organization
dedicated to building better lives for the milli
fected by mental illness. Their website provides mental health education for families and peer-led support groups for individuals and
families. They also have online discussion groups and information
on how to get involved in advocacy.
Helpline: Text “Helpline” to 62640 or call 1-800-950-NAMI (6264)
Mo
nday–Friday 10
trained and can provide information, referrals, and resources.
A.M. to 10 P.M. Eastern time. Volunteers are
ons of Americans af-
Al-Anon Family Groups
Al-Anon (https://al-anon.org) is a mutual support program for
those whose lives have been impacted by a loved one’s substance
use. Their site helps people locate local support groups.
RESOURCES FOR CLINICIANS
National Institute on Drug Abuse
The National Institute on Drug Abuse (NIDA) sites listed here
provide summaries of research regarding cocaine and methamphetamine and their associated use disorders.
Cocaine Research Report: What Is Cocaine? https://nida.nih.gov/
publications/research-reports/cocaine/what-cocaine
Methamphetamine Research Report: https://nida.nih.gov/
publications/research-reports/methamphetamine/overview
REFERENCES
Afshar M, Knapp CM, Sarid-Segal O, et al: The efficacy of mirtazapine in the
treatment of cocaine dependence with comorbid depression. Am J Drug
Alcohol Abuse 38(2):181–186, 2012 22221171
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