9

Co-Occurring Substance Use

Disorders and PTSD
Andrew J. Saxon and Tracy L. Simpson
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P osttraumatic stress disorder (PTSD) and substance use disorders

(SUDs) frequently co-occur (Kessler, Sonnega, Bromet, Hughes, &
Nelson, 1995). When the two do co-occur, considerable psychopathologic
interplay typically emerges, suggesting the need for treatment of both
disorders; however, only a sparse evidence base exists to guide optimal
psycho­pharmacologic or psychotherapeutic treatment for patients with
both PTSD and SUD. This chapter reviews the available evidence on treat-
ment of SUD in the presence of PTSD (Berenz & Coffey, 2012; Petrakis
et al., 2006; Riggs & Foa, 2008), mentions SUD-specific treatments that clin-
ical experience suggests should be provided to patients with both dis­orders
even if not yet well studied, and speculates on some interventions that

This chapter was coauthored by an employee of the United States government as part of official duty
and is considered to be in the public domain. Any views expressed herein do not necessarily represent
the views of the United States government, and the author’s participation in the work is not meant
to serve as an official endorsement.
http://dx.doi.org/10.1037/14522-010
A Practical Guide to PTSD Treatment: Pharmacological and Psychotherapeutic Approaches,
N. C. Bernardy and M. J. Friedman (Editors)
Copyright © 2015 by the American Psychological Association. All rights reserved.

135
 Saxon and Simpson

might serve to treat both disorders simultaneously (Kaysen et al., 2014;

Raskind et al., 2007; Simpson et al., 2009; Yeh et al., 2011). Some aspects
of these topics were recently reviewed in detail (Norman et al., 2012).

DIAGNOSIS
Diagnosis of SUD in patients with PTSD ultimately relies on clinical
assessment using Diagnostic and Statistical Manual of Mental Disorders
(DSM; American Psychiatric Association, 2013) or International Classi­
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fication of Disease (ICD) criteria. Attempts have been made to align the
DSM and ICD criteria, and, although they are quite similar, they are not
identical. Whichever system is used, the criteria for making the diagnosis
of SUD are the same across all substances. Regardless of which substance
has caused the problem, by the time an individual has developed a diag-
nosable SUD, the substance use has adversely affected the person’s overall
level of functioning and his or her physical and mental health and often
caused physiologic destabilization.
Screening instruments exist that can help uncover or point the way
toward a potential diagnosis. It is important to recognize that a positive
screen does not constitute a diagnosis. When individuals screen positive,
the screen should be followed up with a complete clinical assessment
using the DSM or ICD criteria to determine if an SUD is present. For
alcohol use disorders (AUDs), the Alcohol Use Disorders Identification
Test (AUDIT) and the AUDIT—Consumption have been widely validated
as self-report screening measures (Bradley et al., 2007; D. M. Donovan,
Kivlahan, Doyle, Longabaugh, & Greenfield, 2006). A one-item screening
measure was recently validated for drug use disorders consisting of the
single question, “How many times in the past year have you used an ille-
gal drug or used a prescription medication for nonmedical reasons?” A
response of one time or greater yields a positive screen (Smith, Schmidt,
Allensworth-Davies, & Saitz, 2010). In diagnosing PTSD, it is important to
be aware that several PTSD symptoms, most notably those in the arousal
and reactivity cluster, overlap appreciably with common alcohol with-
drawal symptoms (Saladin, Brady, Dansky, & Kilpatrick, 1995) and so

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 Co-Occurring Substance Use Disorders and PTSD

care should be taken to ascertain whether these symptoms are present

when withdrawal is not occurring.
Treatment of SUD saves lives. For example, tobacco use (primarily
smoking) is the number one cause of preventable death resulting in one in
four deaths in the United States, mainly from cancers, respiratory disease,
and cardiovascular disease (Jha et al., 2013). Excessive alcohol use is the
fourth leading cause of death, resulting in an estimated 88,000 deaths and
2.5 million potential years of life lost annually in the United States alone,
typically from liver disease, cancers, and cardiovascular disease (Gonzales
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et al., 2014). Drug overdoses now cause more deaths annually than do
motor vehicle accidents (Centers for Disease Control and Prevention,
2014). SUD co-occurring with other psychiatric disorders including PTSD
is common and often worsens the course of those other disorders (Blanco
et al., 2013; Green, Drake, Brunette, & Noordsy, 2007) and is associated
with higher risk for suicide (Schneider, 2009).

TREATMENT STRATEGY
Once a diagnosis is made, the psychopharmacologic and psychothera-
peutic management of various SUDs sit on a continuum in which each
form of treatment has relatively more or less importance. In the treatment
of cannabis and stimulant (cocaine and amphetamines) use disorders, no
Food and Drug Administration (FDA)-approved pharmacotherapies exist,
and although numerous investigations are seeking effective agents, the
mainstay of treatment is psychotherapy. For AUD, the FDA has approved
three medications—naltrexone, disulfiram, and acamprosate; topiramate,
although not approved, has some demonstrated efficacy. However, for most
patients, these medications have only modest efficacy and act as an adjunct
to a foundation of psychotherapeutic intervention. For tobacco use dis­
orders (primarily cigarette smoking), medications and psychotherapy both
double the odds of quitting and may have additive effects, and both should
be used. Opioid use disorders respond exceedingly poorly to behavioral
interventions in the absence of medications, so pharmacotherapy is the
key treatment component with behavioral interventions as an adjunct.

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 Saxon and Simpson

ALCOHOL USE DISORDERS

Turning first to the pharmacotherapies for AUD, alcohol mobilizes endog-
enous opioids in the brain, which likely contribute to its euphoric effects
(Mitchell et al., 2012). Naltrexone via its antagonism of the mu-opioid
receptor putatively makes alcohol less desirable by blocking this euphoria.
Naltrexone comes in both an oral formulation and an extended-release
intramuscular injection that has activity over a 300-day interval and obvi-
ates concerns over adherence to daily oral medication. Disulfiram inhib-
its the enzyme aldehyde dehydrogenase, a key enzyme in the metabolic
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pathway for alcohol, thereby causing a buildup of acetaldehyde that results

in the unpleasant alcohol-disulfiram reaction if an individual consumes
alcohol. Acamprosate and topiramate are proposed to exert their effects
by stabilizing inhibitory and excitatory networks in the brain that may be
dysregulated by prolonged alcohol use. Both naltrexone and disulfiram
reduce alcohol use compared with placebo in veterans with PTSD and
AUD without causing any adverse effects on PTSD symptoms but also not
exhibiting any particular benefit for PTSD (Petrakis et al., 2006). Acam-
prosate has not been studied among individuals with co-occurring PTSD
and AUD. Although not yet examined in individuals with both disorders,
topiramate did demonstrate efficacy for civilian PTSD in a double-blind,
placebo controlled trial (Yeh et al., 2011) and thus warrants further study
in individuals with co-occurring PTSD and AUD.

TOBACCO USE DISORDERS

Moving to pharmacotherapies for tobacco use disorder, five forms of nic-
otine replacement therapy (NRT) are FDA approved, with three forms—
patch, gum, and lozenge—available over the counter. The nicotine patch
comes in three dosage strengths, 21 mg, 14 mg, and 7 mg, which all have
a 24-hour duration of action. Most regular tobacco users are started on
21 mg, which supplies roughly the equivalent of the nicotine in a pack
of cigarettes, and then use the lower dosage forms to taper off nicotine
once abstinence from tobacco is well established. Lighter users of tobacco
could potentially start treatment with the lower dosage forms. The gum

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 Co-Occurring Substance Use Disorders and PTSD

and lozenge each come in 2- and 4-mg formulations. The 2-mg formula-
tion is for smokers who smoke their first cigarette of the day more than
30 minutes after awakening, and the 4 mg is for smokers who smoke their
first cigarette within 30 minutes of awakening. These products can be used
every 1 to 2 hours with gradual reduction in dosage after tobacco absti-
nence is achieved. The nicotine inhaler is a device that allows the user to
puff and deliver a dose of nicotine to the oral mucosa from whence it is
absorbed. The inhaled nicotine does not go into the lungs. Cartridges each
containing 4 mg of nicotine (of which only 2 mg is absorbed) are placed
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in the device until each cartridge is used up after about 80 inhalations.

Individuals quitting can use six to 16 cartridges per day with gradual
reduction in dosage once tobacco abstinence is achieved. Nicotine nasal
spray delivers about 0.5 mg of nicotine per spray. The user delivers one
spray to each nostril every 1 to 2 hours or even more frequently with a
maximum of 80 sprays per day; dosage is then gradually reduced once
tobacco abstinence is achieved. Nicotine replacement that combines both
long-acting and as needed formulations (e.g., patch plus gum or lozenge)
is strongly recommended as a first-line approach because the combina-
tion has superior efficacy to either alone without any added safety con-
cerns (Fiore, Jaén, & Baker, 2008), and use in hundreds of veterans with
PTSD did not indicate any tolerability issues specific to PTSD (McFall
et al., 2010).
Bupropion is an antidepressant that purportedly blocks the reuptake
of the neurotransmitters dopamine and norepinephrine from the syn-
apse and has antagonist properties at nicotinic receptors. It was evaluated
in a small, double-blind, placebo-controlled trial for smoking cessation
in veterans with PTSD with some promising evidence for efficacy and
no evidence for serious adverse events (Hertzberg, Moore, Feldman, &
Beckham, 2001). Varenicline, the most efficacious approved smoking ces-
sation pharmacotherapy (Fiore et al., 2008), is a partial agonist at the
alpha4-beta2-nicotinic receptor that mimics some of the reinforcing
activity of nicotine while simultaneously blocking nicotine’s access to the
receptor. Varenicline has an FDA-required boxed warning for psychiatric
side effects, although rigorous investigations indicate that, except for sleep

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 Saxon and Simpson

disturbance and abnormal dreams, varenicline does not have an elevated

psychiatric risk profile above other tobacco-cessation medications or pla-
cebo (Garza, Murphy, Tseng, Riordan, & Chatterjee, 2011). Nevertheless,
because sleep disturbance and nightmares are hallmarks of PTSD and a
retrospective chart review suggested an increase in psychiatric symptom-
atology among veterans with PTSD treated with varenicline (Campbell
& Anderson, 2010), varenicline should be used with close monitoring in
individuals with PTSD.
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OPIOID USE DISORDERS

Approved pharmacotherapies for opioid use disorders include metha-
done, buprenorphine, and naltrexone. Methadone acts as a full agonist
at the mu-opioid receptor and stimulates it, thus replacing the opioids
that were misused. In the United States, methadone can only be pro-
vided through federally licensed and accredited opioid treatment pro-
grams and is dispensed daily under observation during the initial stages of
treatment, which offers often-needed structure but does impose lifestyle
limitations. In a randomized controlled trial, methadone, compared with
psycho­social intervention without medication, was significantly better at
reducing illicit opioid use, keeping patients in treatment, and reducing
mortality over a 2-year period (Gunne & Gronbladh, 1981). Preliminary
studies suggest that methadone maintenance is effective in treating opioid
use disorder among individuals with PTSD (Himelhoch et al., 2012).
Buprenorphine is a partial mu-opioid agonist that also binds to the
opioid receptor but does not activate it to the same degree as does a full
agonist such as methadone, yet still serves to replace the misused opioids.
Because of the lower degree of activation, the risk of a fatal overdose on
buprenorphine alone is vanishingly small compared with that risk with
full agonist opioids. For that reason, buprenorphine can be prescribed by
appropriately trained physicians for patients to obtain at a pharmacy and
self-administer. In a randomized controlled trial, buprenorphine main-
tained patients in treatment significantly longer and reduced mortality
in a 1-year period compared with placebo (Kakko, Svanborg, Kreek, &

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 Co-Occurring Substance Use Disorders and PTSD

Heilig, 2003). In the United States, buprenorphine is usually prescribed for

opioid use disorder as a sublingual formulation in combination with the
opioid antagonist naloxone. Naloxone has poor bioavailability by the sub-
lingual route but discourages misuse by injection because anyone intend-
ing to dissolve and inject the sublingual preparation would be injecting an
antagonist. Buprenorphine has not been specifically studied in individuals
with PTSD.
Naltrexone, as noted, is an opioid antagonist. Before receiving it for
an opioid use disorder, patients must be fully withdrawn from opioids, a
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process that may take 3 to 10 days. Once a patient is on naltrexone, any

effects of opioids are totally blocked. Oral naltrexone has not worked well
for most patients with opioid use disorder because they tend to discon-
tinue taking it. This problem may be circumvented by use of the long-
acting injection form (Krupitsky et al., 2011), but it has not yet been fully
investigated in the United States or among individuals with co-occurring
PTSD and opioid use disorder.

PSYCHOTHERAPY
Psychotherapy interventions for co-occurring PTSD and SUD have only
relatively recently begun to be evaluated. A pressing, but still unanswered,
question in the field is whether the two disorders should be treated in an
integrated, concurrent fashion or sequentially with the SUD component
stabilized before engagement in treatment for the PTSD. Most of the psycho­
therapy research in this area has focused on the evaluation of various inte-
grated treatments (e.g., B. Donovan, Padin-Rivera, & Kowaliw, 2001; Mills
et al., 2012; Najavits et al., 2007; Triffleman, Carroll, & Kellogg, 1999), and to
our knowledge sequenced care has not yet been formally evaluated. However,
several studies have compared integrated treatments with standard cogni-
tive behavioral (CBT) SUD treatments, and so it is possible to tentatively
address the question of whether integrated treatment confers benefit beyond
that derived from addressing the SUD.
This literature was recently reviewed by four research teams (Berenz
& Coffey, 2012; McCauley, Killeen, Gros, Brady, & Back, 2012; Torchalla,

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 Saxon and Simpson

Nosen, Rostam, & Allen, 2012; van Dam, Vedel, Ehring, & Emmelkamp,
2012). Torchalla et al. (2012) conducted a meta-analysis on the 17 avail-
able treatment outcome studies, nine of which were randomized clini-
cal trials. Their within-subject results, which included only patients who
received an integrated treatment for PTSD and SUD and compared base-
line values with the longest available follow-up assessment, indicated that
there was a medium overall effect size for SUD outcomes and a large effect
size for PTSD outcomes. However, the between-subjects results involving
only those studies that included a control condition, which typically con-
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sisted of an SUD-only treatment, did not find a reliable difference between

integrated treatment and the control conditions on SUD outcomes and
only a marginally significant difference favoring integrated treatment for
PTSD outcomes.
The reviews by Berenz and Coffey (2012), McCauley et al. (2012), and
van Dam et al. (2012) were all narrative and divided the interventions into
those that did and those that did not involve specific trauma exposure
elements. Each of the reviews concluded that the non–trauma-focused
CBT interventions did not confer added benefit compared with stan-
dard SUD interventions either with regard to substance use outcomes or
PTSD. Only a handful of studies involving trauma-focused interventions
have been published to date, and the consensus across the reviews is that
patients who completed the protocols reported reduced PTSD, although
generally not reduced SUD behaviors relative to control conditions. The
exposure-based interventions were, however, also typically associated with
high dropout.
A recent randomized clinical trial that was not included in the reviews
compared Concurrent Treatment of PTSD and Substance Use Disorders
Using Prolonged Exposure (COPE) plus SUD treatment to SUD treat-
ment alone and also found high dropout rates such that just over half
actually received any exposure sessions and only 18.2% completed all
13 sessions (Mills et al., 2012). There was a significant Group × Time interac-
tion in the intent-to-treat analyses, with those randomized to COPE report-
ing less severe PTSD relative to the standard SUD treatment comparison
group at the 9-month follow-up. There was not, however, a significant

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effect of treatment assignment on substance use outcomes, although both

groups reduced the number of drug classes used, and the rate of sub-
stance dependence fell significantly from baseline to 9-month follow-up.
Two other randomized clinical trials are currently evaluating integrated
trauma-focused exposure-based interventions for PTSD–SUD (Coffey,
Schumacher, & Stasiewicz, 2012; Riggs & Foa, 2008).
All four reviews noted that methodological limitations, including
uncontrolled trials, small sample sizes, and unblinded assessment, ham-
per our ability to determine whether integrated treatments for PTSD–
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SUD hold promise for better outcomes than nonintegrated treatments.

It is noteworthy that SUD treatment alone appears to be beneficial for
both SUD and PTSD outcomes, and Torchalla et al. (2012) suggested that
despite the strong theoretical rationale for integrated treatments, it is
possible that SUD treatments help to alleviate PTSD through a variety of
nonspecific factors (e.g., therapeutic alliance) or perhaps generalization
of SUD-oriented skills to trauma-related issues. There is also early indica-
tion that treatment focused only on PTSD could be beneficial for people
with PTSD–AUD (Kaysen et al., 2014). Preliminary evidence comes from
a large open-trial evaluation of an empirically supported treatment for
PTSD, cognitive processing therapy (CPT; Resick, Nishith, Weaver, Astin,
& Feurer, 2002), in a Veterans Affairs clinical setting that compared veter-
ans with PTSD with no history of AUD, past AUD, and current AUD. The
three groups were not found to differ with regard to the number of ses-
sions attended (average was nine), and all three groups reported signifi-
cant decreases in PTSD and depression severity. Substance use was not
reported. Kaysen and Simpson have a randomized clinical trial underway
comparing CPT, relapse prevention, and an assessment-only waitlist con-
dition for individuals with current PTSD and an AUD. The trial involves
daily symptom monitoring during the treatment phase to evaluate the
sequence of symptom changes associated with the two active conditions
relative to the control condition (National Institutes of Health/National
Institute on Alcohol Abuse and Alcoholism, grant no. R01AA020252-01).
In summary, the empirical literature regarding how best to intervene
psychotherapeutically for individuals with co-occurring PTSD–SUD is in

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 Saxon and Simpson

its infancy. Rigorous, well-designed clinical trials are necessary to deter-

mine whether some form of integrated treatment can succeed in reducing
both PTSD and SUD behaviors or whether treatments focused on SUD
or on PTSD are sufficient. In the meantime, it is noteworthy that standard
SUD treatments appear to be as beneficial for reducing both substance
use and PTSD symptoms as tailored integrated treatments that are not
exposure-based, which offers some measure of assurance that interven-
tions that are already widely available do have some utility in addressing
this commonly seen comorbidity.
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INTEGRATING PSYCHOTHERAPY
AND PHARMACOTHERAPY
The issue of how to combine integrated behavioral interventions plus SUD-
specific medications for co-occurring PTSD and SUD also demands further
investigation. A randomized controlled trial of an eight-session manualized
smoking cessation intervention for individuals with co-occurring PTSD
and tobacco use disorder, which strongly encouraged the use of smoking
cessation medications, demonstrated that prolonged abstinence rates from
tobacco could be effectively doubled by integrating the treatments so that
both are delivered by a single provider, versus sending PTSD patients to a
smoking cessation clinic (McFall et al., 2010). The patients receiving inte-
grated care had reductions in PTSD symptoms equivalent to reductions
achieved by patients with the interventions separated. Patients in integrated
care received significantly more days of smoking cessation medications,
which mediated nearly 10% of the observed treatment effect. This model
of success at integration of PTSD and SUD treatment, along with SUD
pharmacotherapy, encourages investigation of its application to other co-
occurring SUDs.
A recently completed clinical trial enrolled participants with co-
occurring PTSD and alcohol dependence and randomized them to one
of four study conditions: (a) prolonged exposure therapy plus naltrexone
100 mg/day; (b) prolonged exposure therapy plus placebo; (c) support-
ive counseling plus naltrexone 100 mg/day; (d) supportive counseling

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 Co-Occurring Substance Use Disorders and PTSD

plus placebo (Foa et al., 2013). All participants showed large decreases
in number of days using alcohol, with naltrexone-treated participants
using on significantly fewer days than placebo-treated participants. All
participants also showed large decreases in PTSD symptoms without any
noted differences between conditions. This study also supports the idea
that treatments for PTSD and SUD can be successfully delivered in an
integrated fashion.
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SIMULTANEOUS PHARMACOTHERAPY
FOR SUD AND PTSD
In addition to integrating psychotherapies, the notion of using a single
medication or combination of medications for pharmacologic manage-
ment of both disorders simultaneously holds some intrigue. The potential
promise of topiramate has already been mentioned. The antihypertensive
medication prazosin, which blocks alpha-1 adrenergic receptors, has been
studied for more than a decade as a treatment for PTSD-related night-
mares and other symptoms (Raskind et al., 2007) and has come into fairly
widespread use. In a small, double-blind, placebo-controlled trial, prazo-
sin significantly reduced alcohol use in men with alcohol dependence but
without PTSD, suggesting that it may have independent efficacy for alco-
hol dependence (Simpson et al., 2009). Trials are now underway to explore
the efficacy of prazosin for patients with co-occurring alcohol dependence
and PTSD. Sertraline is an FDA-approved pharmacotherapy for PTSD.
Sertraline and naltrexone combined have efficacy for co-occurring depres-
sion and AUD (Pettinati et al., 2010), raising the question of what this
combination might do for co-occurring PTSD and AUD.

CONCLUSIONS AND CLINICAL MANAGEMENT

In conclusion, some promising avenues are being explored to find the
most effective and most parsimonious ways to combine and integrate
pharmacotherapies and psychotherapies for co-occurring PTSD and SUD,
but definitive answers await additional investigation. At this juncture, a

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 Saxon and Simpson

patient with co-occurring PTSD and SUD should receive appropriate

pharmacotherapy for the specific SUD being addressed and appropriate
pharmacotherapy for PTSD. Additionally, the patient should receive an
evidence-based psychotherapy for at least one of the conditions initially,
perhaps determined by patient and provider preference, and then receive
psychotherapy for the other disorder if signs and symptoms of the other
disorder remain poorly controlled.

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