Assessing and treating mood disorders in individuals with substance abuse

C l i n i c a l r e s e a r c h
Assessment and treatment of mood disorders
in the context of substance abuse
Bryan K. Tolliver, MD, PhD; Raymond F. Anton, MD
Overview: the prevalence of
comorbid mood disorders and
substance use disorders
Affective disorders and substance use disorders
(SUDs) are highly prevalent in the general popula-
tion, and their co-occurrence is common.1-7 In general,
comorbid SUDs are associated with a significantly
worse course of illness in both major depressive dis-
order (MDD)8 and bipolar disorder,9 each of which is
known to be among the leading causes of global bur-
Copyright © 2015 AICH – Servier Research Group. All rights
reserved 181 www.dialogues-cns.org
Keywords: addiction; alcoholism; bipolar disorder; comorbidity;
dual diagnosis;
major depressive disorder; suicide
Author affiliations: Addiction Sciences Division, Department of
Psychiatry
and Behavioral Sciences, Medical University of South Carolina,
Charleston,
South Carolina, USA

Address for correspondence: Bryan K. Tolliver, MD, PhD,
Associate Pro-
fessor, Addiction Sciences Division, Department of Psychiatry
and Behav-
ioral Sciences, Medical University of South Carolina, 67
President Street,
Charleston, SC 29425, USA
(e-mail: [email protected])
Recognition and management of mood symptoms in individuals
using alcohol and/or other drugs represent a daily
challenge for clinicians in both inpatient and outpatient
treatment settings. Diagnosis of underlying mood disorders
in the context of ongoing substance abuse requires careful
collection of psychiatric history, and is often critical for op-
timal treatment planning and outcomes. Failure to recognize
major depression or bipolar disorders in these patients
can result in increased relapse rates, recurrence of mood
episodes, and elevated risk of completed suicide. Over the
past decade, epidemiologic research has clarified the prevalence
of comorbid mood disorders in substance-dependent
individuals, overturning previous assumptions that depression in
these patients is simply an artifact of intoxication
and/or withdrawal, therefore requiring no treatment. However,
our understanding of the bidirectional relationships
between mood and substance use disorders in terms of their
course(s) of illness and prognoses remains limited. Like-
wise, strikingly little treatment research exists to guide clinical
decision making in co-occurring mood and substance
use disorders, given their high prevalence and public health
burden. Here we overview what is known and the salient
gaps of knowledge where data might enhance diagnosis and
treatment of these complicated patients.
© 2015, AICH – Servier Research Group Dialogues Clin
Neurosci. 2015;17:181-190.

den of disease.10 Long recognized clinically, the high
prevalence of SUDs in those with mood disorders has
been confirmed over the past 25 years in three large
epidemiologic studies: the Epidemiologic Catchment
Area (ECA) study,11 the National Comorbidity Study
(NCS),12 and the National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC).1-3 Of
these, the NESARC survey provides the most com-
prehensive, up-to-date data on psychiatric comorbid-
ity. Whereas the ECA (n=20 291) and NCS (n=8098)
surveys were based on DSM-III and DSM-III-R cri-
teria, respectively, and did not measure substance de-
pendence as a syndrome,2 data from NESARC (n=43
093) indicate that the 12-month prevalence of DSM-
IV independent mood disorders in the US popula-
tion was 9.21% (12-month and lifetime prevalence of
major depressive disorder [MDD] were 5.28% and
13.28%, respectively, whereas 12-month and lifetime
prevalence of bipolar disorder were 2.0% and 3.3%)1,2
and the rate of DSM-IV substance use disorders in the
previous 12 months was 9.35%.1 As in the ECA and
NCS studies, the NESARC study found significant
co-occurrence of mood disorders and SUDs whether
considered in terms of lifetime or 12-month preva-
lence.1-3 Among respondents with lifetime MDD, over
40% had an alcohol use disorder; 21% had a history of
alcohol dependence, roughly 2-fold the rate in those
without MDD. Among those with MDD in the prior
12 months, more than 14% had an alcohol use disor-
der, and 8.2% met criteria for alcohol dependence.2
Similarly, among respondents with a past-year SUD,
roughly 19.7% had at least one independent mood

disorder during the same 12-month period.1 Comor-
bid SUDs were particularly high in respondents with
bipolar disorder, consistent with the ECA and NCS
studies, both of which identified bipolar disorder as
the Axis I diagnosis most associated with a co-occur-
ring SUD.11,12
Two additional findings from NESARC were note-
worthy for their diagnostic and treatment implications.
First, fewer than 1% of individuals meeting criteria for
a mood disorder in NESARC were classified as hav-
ing substance-induced mood disorder (SIMD), a distur-
bance of mood that was exclusively attributable to sub-
stance use or withdrawal rather than an exacerbation of
underlying MDD or bipolar disorder.1 This result sup-
ported an earlier finding from the 1992 National Lon-
gitudinal Alcohol Epidemiologic Survey indicating that
prior, but not current alcohol dependence increased the
risk of current MDD more than 4-fold.13 These results
from two separate general population samples contra-
dict previous data, acquired from almost 3000 treated
alcohol-dependent subjects and their relatives, that had
suggested that a significant proportion of mood disorder
diagnoses were largely attributable to alcohol-induced
affective symptoms.14 Second, importantly, the propor-
tion of respondents with independent mood disorders
was significantly higher in treatment-seeking persons
than in the overall sample. Specifically, among respon-
dents with DSM-IV SUDs who sought substance abuse
treatment in the past 12 months, the 12-month preva-
lence of co-occurring independent mood disorders was
over 40%.1
The clinical implications of these findings from
NESARC and earlier epidemiologic studies are clear
and important. Independent mood disorders are com-

mon in individuals who use alcohol and drugs, espe-
cially in those seeking substance abuse treatment,
and in many individuals the mood disturbance cannot
be attributed to the acute effects of substance use or
withdrawal. These results indicate that clinicians in
addiction treatment settings must address co-occur-
ring mood disorders, just as clinicians in primary care
and mental health settings should assess for SUDs.
This suggestion, however, does not mitigate the diffi-
culty of differentiating between a substance-induced
comorbid-state vs two independent but exacerbating
conditions in the assessment of the dual-diagnosis
patient. Further, the findings from NESARC suggest
that treatment should not be withheld from substance-
dependent individuals whose independent mood dis-
orders are in remission on the assumption that mood
symptoms are, or were, attributable to intoxication
or withdrawal and thus must have resolved with ab-
stinence.1,2 The present review will further address
these clinical implications separately with regard to
their significance for diagnosis, course of illness and
prognosis, as well as treatment. It is not intended to
systematically compile and compare all literature on
various SUDs (eg, alcohol use disorders vs cocaine,
opioid, sedative, or cannabis use disorders), but rather
will instead focus on current knowledge gaps and op-
portunities for advancement of research priorities, as
well as improvement of clinical care as they pertain
to assessment and treatment of mood disorders in the
context of comorbid substance abuse.
182
Mood disorders and substance abuse - Tolliver and Anton

Dialogues in Clinical Neuroscience - Vol 17 . No. 2 . 2015
Diagnostic challenges
Controversy regarding diagnosis has been a persis-
tent impediment to progress in understanding the re-
lationships between mood disorders and SUDs. Given
the absence of validated clinical biomarkers for either
MDD or bipolar disorders,15 misdiagnosis of mood dis-
turbance in the context of active substance abuse is a
legitimate concern. It has long been appreciated that af-
fective symptoms are common in substance-dependent
patients in treatment but often change or resolve over
time with lengthening abstinence.16,17 This observation,
as well as the fact that intoxication and/or withdrawal
from alcohol and other drugs of abuse can induce states
that mimic symptoms of independent mood disor-
ders18,19 complicate the diagnosis of MDD and bipolar
disorders in patients with SUDs who are actively abus-
ing substances at the time of assessment. Consequently,
the importance of distinguishing independent (prima-
ry) mood disorders from substance-induced (second-
ary) mood disorders has long been emphasized19 as
both over- and underdiagnosis of mood disorders have
been shown to occur in patients with SUDs.20,21
A traditional approach to the diagnostic dilemma
is to withhold pharmacologic treatment for depression
for a period of time after abstinence is established in
order to determine whether, and to what extent, mood
symptoms are attributable to substance use. By con-
vention, treatment delay is often at least 1 month, con-
sistent with the DSM-IV course specifier for early full
remission from substance dependence and as described
in Criterion C for Substance-Induced Mood Disorder
in DSM-IV.22 Unfortunately, delaying treatment for
mood symptoms can be problematic for a number of

reasons. First, patients may be unable to establish or
sustain abstinence for a month or longer. In the case of
substances like alcohol or benzodiazepines, establish-
ing abstinence may require medically managed inpa-
tient detoxification due to potentially life-threatening
withdrawal. While this generally requires only a rela-
tively short time in acute care settings depending on the
complexity of withdrawal, after discharge patients often
return to their home environment where the risk of re-
lapse in the first 30 days is high. For instance, Kiefer and
colleagues found that following inpatient detoxifica-
tion (typically much longer in Europe than in the US),
65% of untreated subjects had consumed alcohol and
50% had returned to heavy drinking within 2 weeks of
discharge.23 Patients with untreated depression are at
higher risk to return to drinking or drug use and tend to
do so more quickly.
In a cohort of patients hospitalized for alcohol de-
pendence who were followed monthly for 1 year after
discharge, Greenfield and colleagues found that a diag-
nosis of major depression at inpatient treatment entry
was associated with a shorter time to first drink (38 days
vs 125 days) as well as a shorter time to full relapse (41
days vs 150 days) compared with patients without major
depression at admission.24 Furthermore, depressed al-
cohol-dependent subjects who were discharged without
antidepressants were likelier to return to drinking than
were their antidepressant-treated counterparts. Where-
as virtually all depressed subjects discharged without
antidepressants had relapsed in the first 100 days after
discharge, 20% of those depressed subjects discharged
on antidepressants remained abstinent at 1 year.24 In-
terestingly, no statistically significant differences were
found in time to first drink or relapse in depressed sub-
jects who were initially classified as having independent

MDD vs those classified as having substance-induced
depression.24 Similarly, Hasin and colleagues followed
250 inpatients with cocaine, heroin, or alcohol depen-
dence at 6, 12, and 18 months after discharge from index
hospitalization, roughly 60% of whom were diagnosed
with co-occurring depression. Depressed patients were
retrospectively classified into three subgroups: those
with premorbid MDD prior to the development of sub-
stance dependence, those meeting criteria for MDD
during sustained abstinence during follow-up, or those
considered to have exclusively substance-induced de-
pression.25 The subjects with premorbid MDD or sub-
stance-induced depression were significantly more like-
ly to meet criteria for substance dependence during the
follow-up period. Of the patients (n=133) who did not
use any substances for at least 26 consecutive weeks,
those who experienced a major depressive episode dur-
ing this time were subsequently three times as likely to
relapse into dependence during the follow-up period.25
Given these findings, it is especially concerning that
substance-dependent patients with a history of major
depressive episode(s) are significantly likelier to have
attempted suicide regardless of whether the depression
first occurred before or during substance use.26 These
data underscore the importance of collecting a compre-
hensive psychiatric history that addresses relative onset
of mood symptoms and substance abuse in all patients
183
with SUDs, and also suggests that caution is warranted
in withholding or delaying treatment in these patients.

Conversely, many people who have underlying alco-
hol and other substance use disorders present to primary
care and/or mental health professionals with complaints
of depression, anxiety, and insomnia. Here again a good
history of alcohol and substance use is crucial but, as
most clinicians recognize, many patients will not provide
accurate information regarding the drinking and sub-
stance use, reducing diagnostic accuracy. Fortunately, in
this case, laboratory tests including urine drug screens
and urine/serum biomarkers of alcohol use can be help-
ful in establishing the appropriate diagnosis. While this
is beyond the scope of this review, suffice it to say that
there are three tests available that are useful to estab-
lish any recent alcohol use (urinary ethylglucuronide
[EtG]), moderate to heavy use (phosphatidyl ethanol),
and heavy harmful use,(carbohydrate deficient transfer-
rin [%CDT]). Readers are referred to a salient review of
this topic by Litten and colleagues.27 In addition to these
laboratory aids, clinicians should be suspicious of alcohol
or drug abuse underlying psychiatric complaints when:
(i) there is a past history of substance abuse; (ii) there
is a family history of substance abuse; (iii) there are co-
occurring or past medical disorders associated with alco-
hol or substance abuse (eg, GI conditions, trauma, HIV,
HCV, macrocytic anemia, high uric acid, smoking); (iv)
there are chronic pain complaints; (v) multiple relation-
ship problems; (vi) numerous job changes; (vii) legal dif-
ficulties such as DUIs, public intoxication charges, and
assault arrests including domestic violence.
Course of illness and prognosis
The interrelationships of diagnosis, prevalence, illness
course, and treatment are fundamental to all medical
practice but are especially important in the realm of
psychiatric comorbidity. Accurate diagnosis is essential

to understanding a given individual’s prognosis as well
as for formulating a treatment plan. Conversely, under-
standing the natural history of a given disease, and its
likely responsiveness to treatment, may aid in diagnos-
ing it accurately as individuals with the disorder(s) are
longitudinally monitored and treated over time. For
example, given the high prevalence of both depression
and SUDs, it is reasonable to expect high rates of mood
episodes that are attributable primarily or exclusively
to substance use and that do not recur unless active
substance use is resumed. However, this has not been
found to be universal in either clinical samples28,29 or
in epidemiologic studies.1,30 For instance, Ramsey et al
found that over 25% of treatment-seeking alcoholics
first diagnosed with SIMD at baseline were reclassified
as having MDD over the following year of follow-up.28
Similarly, in inpatients with alcohol, cocaine, or opioid
dependence followed for 1 year after discharge, Nunes
and colleagues reported that 57% met DSM-IV criteria
for a major depressive episode.29 Whereas 51% of the
sample had initially been classified as having SIMD at
admission, only 14% of depressed patients were clas-
sified as having SIMD at follow-up. Patients initially
classified as having substance-induced depression at
baseline were equally likely to have a major depressive
episode during follow-up compared with those initially
classified as having MDD; in the group of depressed
patients as a whole, the mean number of weeks spent
depressed over 12 months was 25.6 (SD 15.3).29 Recent
analysis of data from Wave 2 of NESARC, conducted
approximately 3 years after the original survey, has
allowed this question to be addressed in a nonclini-
cal sample of over 2000 respondents who met lifetime
criteria for MDD and SUD at Wave 1. Of the 106 re-
spondents classified as having SIMD in Wave 1 (only

0.26% of depressed respondents with SUDs), 88 were
resurveyed in Wave 2; of these, 95% of those who had
experienced a depressive episode between Waves 1 and
2 were reclassified as having MDD.31
In the case of bipolar disorders and comorbid
SUDs, the situation is particularly complex because:
(i) the mood and substance illnesses are likely to ex-
ert bidirectional influences on each other; and (ii) they
rarely occur alone in the individual patient in the ab-
sence of other comorbid psychiatric conditions, any of
which may contribute to illness severity. For example,
in bipolar disorder comorbid SUDs are associated with
early age of onset,32 high rates of smoking,33 and fre-
quent co-occurrence of anxiety disorders,34-37 attention
deficit/hyperactivity disorder,38 and personality disor-
ders,39 each of which is associated with a more severe
course of affective illness. Accordingly, it is difficult to
know to what extent comorbid SUDs are contributory
per se, but it is well established that alcohol and drug
dependence are associated with poor clinical outcomes
in patients with bipolar disorder. Though exceptions
have been reported,40,41 comorbid SUDs are associat-
ed with poor treatment adherence,42 longer, more fre-
184
quent mood episodes,43 more mixed manic-depressive
episodes,44-46 and lower functional recovery, even during
abstinence,47 suggesting that SUDs may be a marker
rather than a determinant of bipolar illness severity. As

a result, bipolar patients with SUDs have higher utili-
zation of emergency services,48 and more hospitaliza-
tions49,50 compared with bipolar patients without SUD.
Comorbid SUDs also predict poor response to lithium,
a standard mood-stabilizing treatment of bipolar disor-
der.46,51,52 Of particular concern, SUDs are often accom-
panied by increased impulsivity and suicidality in those
with bipolar disorder53,54; in fact the risk of attempted
suicide in bipolar alcoholics is almost twice that of non-
alcoholic bipolar patients.55-58 Tragically, 14% to 16%
of those with bipolar disorder and co-occurring SUDs
complete suicide.59
Despite the high prevalence of comorbidity of mood
disorders and SUDs, prospective data regarding prog-
nostic factors for either mood or substance use out-
comes are sparse and somewhat inconsistent. Whereas
most early prospective studies found that substance
abuse was associated with increased syndromal mood
recurrence and shorter time in remission in bipolar dis-
orders,60-64 other investigators have noted that spacing
of follow-up visits in these studies tended to be long and
quite variable, and that actual amounts of substance in-
take received little or no attention.41
Results of subsequent prospective research have
been mixed. The 3-year course of 51 patients with bipo-
lar disorder and comorbid SUDs enrolled in the New
Hampshire Dual Diagnosis Study was characterized by
substantial improvement in substance abuse outcomes
(61% in full remission at 3 years) and functional sta-
tus but only modest improvement in bipolar symptoms,
with weak relationships among outcome domains.65 In
contrast, van Zaane and colleagues reported wide vari-
ability in alcohol use with no appreciable association
with psychiatric symptoms or functional status among a
cohort of bipolar alcoholics followed prospectively for 1

year.41 More recently, Farren and colleagues found that
drinking outcomes improved and depression severity
generally lessened in alcohol-dependent patients with
either MDD or bipolar disorder (as did mania severity
in bipolar alcoholics) who were followed over 5 years.66
This group found that there was no correlation between
either depression severity (as measured by the Beck
Depression Inventory [BDI]) or mania severity (as
measured by the Young Mania Rating Scale [YMRS])
and abstinence or number of drinking days at 5 years,
but that both BDI and YMRS scores were positively
correlated with units of alcohol consumed per drink-
ing day.66 In this cohort, drinking outcomes at 5 years
were best predicted by drinking outcomes at earlier
time points and were not associated with age, gender, or
mood diagnosis.
Unfortunately, these studies are unable to address a
question that is likely to be relevant to clinicians treat-
ing patients who are early in recovery67,68: specifically,
what are the relationships between the trajectories of
mood symptoms and substance use in the near term?
If patients remain abstinent, will mood outcomes im-
prove automatically? Conversely, if mood stability is
achieved, are substance use outcomes necessarily im-
proved? Stated another way, does substance abuse pre-
cede depression69 or vice versa? To address this ques-
tion, two analyses of data from an 8-week randomized
placebo-controlled trial of acamprosate in alcohol-de-
pendent subjects with bipolar disorder were conducted
by Prisciandaro and colleagues.70,71 In the first analysis,
comorbid anxiety disorders were prospectively associ-
ated with increased depressive symptoms and alcohol
use over the 8-week trial period, as were the use of ei-
ther antipsychotic or anticonvulsant medications.70 In
the second analysis, this group applied a novel statisti-

cal method (hidden Markov modeling) to assess week-
to-week prospective relationships among depressive
symptoms, alcohol craving, and alcohol use.71 Contrary
to previous work suggesting that depression is likely to
be precipitated by alcohol use,69 the latter study found
that depressive symptoms and alcohol craving predict-
ed proximal alcohol use 1 week later, whereas the re-
ciprocal relationship was not observed.71 Though these
results were limited to alcohol use and require indepen-
dent replication in a larger sample, they underscore the
importance of addressing mood symptoms in addition
to emphasizing abstinence in patients with co-occurring
mood disorders and SUDs.
In summary, the relationship between the respective
course of illness of co-occurring mood disorders and
SUDs appears to be complex and incompletely under-
stood at this time. As such, it may be wise to question
assumptions about how mood and substance use disor-
ders influence each other in given individuals or clinical
populations as a whole. Considerably more research re-
garding course of illness is warranted given the obvious
implications for treatment.
185
186
Treatment of co-occurring mood and
substance use disorders
Traditionally the approach to treating SUDs in the
Unites States has been psychosocial counseling, usu-

ally in a combination of group and individual settings.
Though progress has been made in the development
of integrated group therapy72 and in application of es-
tablished behavioral approaches such as contingency
management73 in patients with co-occurring SUDs and
mood disorders, the present review will restrict the
discussion to the current evidence base for pharma-
cotherapy in these patients. A number of critical ques-
tions encountered regularly in clinical practice remain
unanswered regarding pharmacotherapy for comorbid
mood and substance use disorders. For example, is it
essential that the mood disorder be independent (pri-
mary) to benefit from mood-stabilizing medications or
can those that also have substance-induced (secondary)
mood symptoms benefit from these medication(s)?
Should treatment of affective symptoms and substance
abuse proceed simultaneously or in staged/sequenced
fashion? If sequenced, in what order should treatment
proceed? Can depression and/or mania be treated suc-
cessfully in patients who continue to drink or use drugs
heavily? Conversely, can patients with severe substance
use disorders establish and maintain sobriety without
adequate treatment of mood instability? Can any in-
dividual medications effectively treat both conditions,
or are combinations of medicines necessary? Unfortu-
nately, empirical data that may help address these im-
portant questions are sparse, in part because individuals
with SUDs are traditionally excluded from medication
trials for MDD and bipolar disorder, and likewise most
clinical trials of agents for treating SUDs exclude other
Axis I psychiatric conditions.5-7
In the case of patients with MDD and comorbid
SUDs, the majority of previous research has focused
on the use of antidepressants.5 In the era predating the
development of selective serotonin reuptake inhibitors
(SSRIs), safety concerns regarding the potential for fa-

tal overdose on tricyclic antidepressants or monoamine
oxidase inhibitors impeded both research and clinical
use of these drugs in depressed patients with comorbid
SUDs. A 2004 meta-analysis by Nunes and Levin found
that of clinical research focusing on comorbid SUD and
mood disorders conducted at the time, only one third
(14 of 44) of studies met criteria as adequately place-
bo-controlled, double-blind, randomized prospective
clinical trials.74 This meta-analysis found evidence for
a modest beneficial effect of antidepressants on mood
symptoms in depressed subjects with SUDs but noted
high heterogeneity of effects across studies, with virtu-
ally no effects evident on substance use outcomes ex-
cept in trials with depression effect sizes >0.5. As Nunes
and Levin noted, a number of moderators of depression
outcomes (eg, placebo response, sample characteristics,
time of depression diagnosis, etc) were found, thereby
preventing extrapolation between antidepressant ef-
ficacy and effects on substance use outcomes in these
trials, either within or between studies included in the
meta-analysis.74 Pettinati reported similar findings in
a review of antidepressant trials in depressed alcohol-
ics, with 75% of the trials finding benefit for reduction
of depressive symptoms but only a minority reporting
beneficial effects on drinking outcomes.75 Interestingly,
a large multisite trial of sertraline (50 to 150 mg) that
enrolled 345 alcohol-dependent subjects with MDD
found no superiority of sertraline over placebo for ei-
ther depression or drinking outcomes.76 Importantly,
this trial randomized based on secondary versus inde-
pendent depression distinction and generally found no
differences based on this classification.
More recently, Pettinati and colleagues reported a
significant effect of the combination of sertraline with
the opioid antagonist naltrexone, one of 3 FDA-ap-

proved medications for the treatment of alcohol depen-
dence, in reducing drinking in depressed alcohol-depen-
dent subjects.77 In this trial, subjects were randomized
to sertraline, naltrexone, the combination of sertraline
plus naltrexone, or double placebo for 14 weeks while
receiving weekly cognitive behavioral therapy. The
group receiving the combination of sertraline and na-
ltrexone had a significantly higher rate of abstinence
(53.7%) that was in fact double that of the comparison
groups (21.3% to 27.5%).77 In addition, subjects in the
combination group exhibited a significantly longer de-
lay to relapse to heavy drinking than those in any of the
comparison groups. Though differences in the improve-
ment of depression scores among groups fell just short
of statistical significance, this outcome also tended to
favor sertraline plus naltrexone combination treatment.
The combination therapy was well tolerated relative to
the other treatment groups. The study by Pettinati et
al77 is a landmark in dual-diagnosis treatment research
that may have immediate impact on clinical practice,
suggesting that treating both MDD and alcohol use
disorder simultaneously with medications indicated for
each condition should be a treatment standard—again
emphasizing the need for good assessment and diagno-
sis. Also, while Pettinati et al did not investigate the psy-
chotherapeutic/counseling component, it is likely that
more than routine medication visits might be needed to
successfully treat these comorbid patients. In another
comorbid alcohol and MDD study, Moak et al78 found
that sertraline in combination with CBT (similar to that

used in the Pettinati study) reduced drinks per drinking
day compared with placebo and was particularly useful
in reducing depression in women.
In the case of patients with bipolar disorder and co-
morbid SUDs, even less is known about optimal treat-
ment because few randomized controlled medication
trials have been conducted. At present, only nine clini-
cal trials that assessed substance use as the primary out-
come measure in this population have been published.
Three of these trials evaluated subjects with bipolar
disorder and stimulant dependence: one positive trial
of lamotrigine for treatment of bipolar disorder and co-
caine dependence79 and one trial each of the nutritional
supplement citicoline for treatment of bipolar disor-
der and cocaine dependence80 and methamphetamine
dependence,81 respectively. The six other randomized
controlled trials have studied subjects with bipolar dis-
order and co-occurring alcohol dependence, the SUD
most commonly diagnosed in patients with bipolar dis-
order.1,11
Of these six trials, only one has demonstrated ef-
ficacy in reducing drinking. Salloum and colleagues
found that valproate significantly reduced the propor-
tion of heavy drinking days and drinks per drinking day
in alcohol-dependent subjects with bipolar I disorder
when added to lithium and counseling.82 Three trials of
quetiapine,83-85 one trial of naltrexone,86 and one trial
of acamprosate87 did not support the efficacy of these
medications in bipolar alcoholics. Whether this is due to
sample size effects, compliance issues, variability of con-
comitant mood stabilization treatment, or the nature of
the comorbid illness (including genetic and other co-
morbid psychiatric symptoms) is unclear.
Finally, it is worth noting that the paucity of data
from randomized clinical trials is not the only obstacle

to advancing pharmacotherapy of comorbid mood dis-
orders and SUDs. The potential use of addiction main-
tenance therapies such as buprenorphine for treat-
ment-resistant depression has been of interest for over
20 years,88 but has received little empirical study due in
large part to concerns about abuse liability and physical
dependence. Indeed, prevailing opinion of many treat-
ment providers, patients themselves, and society as a
whole continues to impede the use of any drug treat-
ments for addiction in general. Consequently, adoption
of medication-assisted treatment of SUDs in individu-
als with or without mood disorders remains disappoint-
ingly low in the United States.89 Available data suggest
that this is especially the case for patients with comor-
bid mood and substance use disorders. For example, of
the large number of bipolar patients with SUDs who
were enrolled in the Systematic Treatment Enhance-
ment Program for Bipolar Disorder (STEP-BD) study,
only 0.4% were prescribed approved drug therapies
for alcohol or opioid dependence at the time of enroll-
ment.90 Similarly, patients with bipolar disorder tend to
have high rates of cigarette smoking and low rates of
quit attempts,91 yet few psychiatrists discuss smoking
cessation with their patients and a notably smaller pro-
portion combine counseling with approved treatments
for nicotine dependence.92,93
Conclusions
Co-occurring mood disorders and SUDs are common,
and tend to have an adverse impact on both mood and
substance use outcomes. Diagnostic challenges remain
common, though longitudinal clinical studies and large-
scale epidemiologic studies conducted over the past
two decades have begun to elucidate the prevalence
and course of independent vs substance-induced mood

disorders in patients with SUDs and have begun to
pose questions about the appropriateness of withhold-
ing treatment in these patients. Much more research on
prognosis and treatment of comorbid mood and sub-
stance use disorders is urgently needed. o
Acknowledgements: Dr Anton‘s research was supported by K05
grant
number AA017435. Dr Tolliver’s research was supported by
K23 grant
AA017666.
187
188
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Evaluación y tratamiento de los trastornos del
ánimo en el contexto del abuso de sustancias
El reconocimiento y manejo de los síntomas anímicos
en los sujetos que emplean alcohol y/u otras drogas es
un desafío diario para los clínicos en el tratamiento tan-
to de pacientes ambulatorios como hospitalizados. El
diagnóstico de los trastornos del ánimo que están a la
base de un abuso de sustancias requiere de una recopi-
lación cuidadosa de la historia psiquiátrica, y a menu-
do es clave para lograr una planificación terapéutica y
resultados óptimos. Una falla en el reconocimiento en
estos pacientes de la depresión mayor o de los trastor-
nos bipolares puede traducirse en un aumento en la fre-
cuencia de recaídas, recurrencias y episodios anímicos,
y un riesgo elevado de suicidio consumado. Durante la
última década la investigación epidemiológica ha clari-
ficado la prevalencia de los trastornos del ánimo comór-
bidos en sujetos con dependencia de sustancias, dando
un vuelco en los supuestos previos acerca de que la
depresión en estos pacientes era simplemente un arte-
facto de la intoxicación y/o de la abstinencia, y que por
tanto no requería de tratamiento. Sin embargo, aun es

limitada nuestra comprensión acerca de las relaciones
bidireccionales entre los trastornos del ánimo y el abu-
so de sustancias en cuanto a los cursos y pronósticos de
la enfermedad. Asimismo, llama la atención que existe
poca investigación terapéutica para guiar la toma de
decisiones clínicas cuando co-ocurren trastornos del áni-
mo y por uso de sustancias, dada su alta prevalencia y la
carga para la salud pública. En este artículo se repasa lo
que se sabe y los vacíos más destacados del conocimien-
to donde los datos podrían mejorar el diagnóstico y el
tratamiento de estos pacientes complicados.
Évaluation et traitement des troubles de l’humeur
dans le cadre de la toxicomanie
La reconnaissance et la prise en charge des troubles de
l’humeur chez les personnes consommant de l’alcool et/
ou d’autres substances sont des défis quotidiens pour
les médecins, que ce soit dans le cadre hospitalier ou
ambulatoire. Le diagnostic des troubles de l’humeur
sous-jacents dans le contexte d’une toxicomanie exis-
tante nécessite un recueil soigneux des antécédents psy-
chiatriques ; il est souvent déterminant pour une orga-
nisation et des résultats optimaux du traitement. Une
absence de reconnaissance de la dépression majeure ou
des troubles bipolaires chez ces patients peut entraîner
une augmentation des taux de rechute, une récidive des
troubles thymiques et un risque élevé de suicide réussi.
Ces 10 dernières années, la recherche épidémiologique
a clarifié la prévalence des troubles comorbides de
l’humeur chez les personnes dépendantes d’une subs-
tance, infirmant les hypothèses antérieures considérant
la dépression chez ces patients comme un simple arté-
fact de l’intoxication et/ou du sevrage, ne nécessitant
donc aucun traitement. Cependant, notre compréhen-
sion des relations bidirectionnelles entre troubles de

l’humeur et troubles de l’usage d’une substance en
termes d’évolution de la maladie et de pronostic reste
limitée. De même, le peu de recherche thérapeutique
pour guider la décision clinique en cas de troubles
concomitants de l’humeur et de l’usage de substances
est marquant, compte tenu de leur haute prévalence et
de leur poids dans la santé publique. Nous analysons ici
ce qui est connu ainsi que les lacunes importantes dans
nos connaissances dans ce domaine ; des résultats de
recherche pourraient améliorer le diagnostic et le trai-
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190
Family Treatment for Bipolar Disorder and Substance Abuse in
Late Adolescence
David J. Miklowitz
UCLA School of Medicine
The initial onset of bipolar disorder occurs in childhood or
adolescence in about 50% of patients.
Early-onset forms of the disorder have a poorer prognosis than
adult-onset forms and are frequently
characterized by comorbid substance abuse. Clinical trials
research suggests that family psychoeduca-
tional approaches are effective adjuncts to medication in
stabilizing the symptoms of bipolar disorder
in adults and youth, although their efficacy in patients with
comorbid substance use disorders has not
been systematically investigated. This article describes the
family-focused treatment (FFT) of a late
adolescent with bipolar disorder and polysubstance dependence.
The treatment of this patient and
family required adapting FFT to consider the family’s structure,
dysfunctional alliance patterns, and
unresolved conflicts from early in the family’s history. The case

illustrates the importance of conduct-
ing manual-based behavioral family treatments with a
psychotherapeutic attitude, including addressing
unstated emotional conflicts and resistances that may impede
progress. C© 2012 Wiley Periodicals, Inc.
J. Clin. Psychol: In Session 68:502–513, 2012.
Keywords: expressed emotion; family-focused treatment; drug
abuse; lithium; psychoeducation; struc-
tural family therapy
Bipolar disorder (BD) often has its first onset in late childhood
or adolescence. Although there is
substantial evidence for the effectiveness of pharmacotherapy in
early-onset BD, many children
and adolescents have multiple recurrences and psychosocial
impairment, as well as substantial
medication side effects. There is increasing evidence for the
efficacy of adjunctive psychosocial
treatments for both adult and pediatric bipolar disorder
(Miklowitz, 2008).
Approximately 50%–67% of adults with BD report onset of
their first episode before the age
of 18 years and between 15% and 28% before the age of 13
years (Perlis et al., 2004). Patients with
early onset (before 18 years of age) have more severe courses of
illness, more switches of mood
polarity, longer episodes, more comorbid disorders, and more
mixed episodes than adult-onset
BD patients. Each of these clinical features bodes poorly for
long-term outcome (Post et al.,
2010).
There has been a dramatic increase in the community diagnosis
of early-onset BD in the past

10 years, leading some to question whether the diagnosis is a
fad. There is indeed a fair amount
of slippage in the use of the Diagnostic and Statistical Manual,
Fourth Edition (DSM-IV)
diagnostic criteria in the community. However, contrary to
popular belief, clinical studies find
that pediatric-onset BD is equally prevalent across countries
and is not elevated in frequency in
the United States, with a worldwide prevalence of 1.8% (Van
Meter, Moreira, & Youngstrom,
2011).
Adolescents with BD are approximately five times more likely
to also develop substance abuse
disorders (SUDs) than healthy controls. Those with both BD and
SUD are at an increased risk
for suicide attempts, more frequent relapses of mood disorder,
and poor psychosocial functioning
(Goldstein et al., 2008). In some cases, the SUD comes before
the initial onset of mood symptoms,
and in other cases (such as the present case), the reverse. It can
be quite difficult to determine
Support for the preparation of this article was provided by
National Institute of Mental Health Grant Nos.
MH073871 and MH077856.
Please address correspondence to: David J. Miklowitz,
Department of Psychiatry and Behavioral Sciences,
UCLA Semel Institute Rm 58-217, David Geffen School of
Medicine at UCLA, 760 Westwood Plaza, Los
Angeles, CA 90024-1759; e-mail: [email protected]
JOURNAL OF CLINICAL PSYCHOLOGY: IN SESSION, Vol.
68(5), 502–513 (2012) C© 2012 Wiley Periodicals, Inc.
Published online in Wiley Online Library
(wileyonlinelibrary.com/journal/jclp). DOI: 10.1002/jclp.21855

Bipolar Disorder and Family 503
whether an adolescent’s symptoms are the result of mood
disorder, drugs, or both: It appears
that each disorder worsens the other.
This article focuses on family-focused treatment (FFT) with an
adolescent suffering from
both BD and substance abuse disorder. The treatment was
conducted in conjoint sessions with
the patient, his parents, and siblings. As in all cases of FFT, the
structure involved sessions of
psychoeducation about BD, communication enhancement
training, and problem-solving skills
training. To effectively administer these components, the
clinicians had to be flexible and sensitive
to a number of underlying emotional conflicts in this family,
which, they believed, stood in the
way of real change.
Family-Focused Treatment
The treatment of pediatric-onset BD parallels the treatment of
adults, although medication
dosages (typically, mood stabilizers and/or atypical
antipsychotics with adjunctive antidepres-
sants or anxiolytics) are adjusted for age and body weight. FFT,
which is provided in conjunction
with pharmacotherapy, aims to teach patients and family
members about the causes, prognosis,
and self-management of bipolar disorder; how to communicate
more effectively and learn skills
to solve family problems; how to accept the necessity of

ongoing treatment; and how to maximize
the patient’s likelihood of success in reengaging with the
community, school, or workplace.
FFT is conducted in four stages: an engagement phase, in which
the objective is to connect with
the patient and parents (and, where possible, siblings) and relay
information about the treatment’s
structure and expectations; psychoeducation, in which therapists
lead the family in discussions
of the nature, causes, and management of BD symptoms;
communication enhancement training,
in which patients and family members rehearse effective
speaking and listening skills (e.g., how
to give praise and constructive criticism and how to listen
actively); and problem-solving skills
training, in which patients and family members define, generate
and evaluate, and implement
solutions to problems in the family’s or the patient’s life. The
treatment is given in 21 sessions
(12 weekly, 6 biweekly, 3 monthly) over 9 months. When
practiced in the community, clinicians
and families sometimes opt for shorter versions or longer
intervals between sessions.
FFT has been recognized as an empirically supported treatment
for BD by the Ameri-
can Psychological Association’s Society for Clinical
Psychology, and it is listed as the only
one of five therapies to have strong research support for the
treatment of bipolar depression
(www.div12.org/PsychologicalTreatments/index.html). It has
also been included in a shortlist
of exemplary empirically supported treatments (Baker, McFall,
& Shoham, 2008) and is cited as
a preferred psychosocial intervention in most of the psychiatric

treatment guidelines for BD in
adults or children. There are four randomized trials supporting
the effects of FFT in combination
with pharmacotherapy in preventing recurrence or stabilizing
symptoms (Miklowitz & Scott,
2009) after an episode of BD I or II. One large-scale community
effectiveness study indicated the
benefits of adjunctive FFT, interpersonal and social rhythm
therapy, and cognitive-behavioral
therapy in hastening time to recovery and elongating periods of
wellness in adults with bipolar I
or II depression relative to brief care (Miklowitz et al., 2007). A
two-site trial of adolescents with
BD indicated that FFT and pharmacotherapy were more
effective than brief psychoeducation
and pharmacotherapy in reducing time to recovery from
depressive symptoms, the amount of
time in depressive episodes, and the severity of inter-episode
depressive symptoms over 2 years
(Miklowitz et al., 2008).
Theoretical Basis of FFT
The symptoms of BD affect the emotional responses of
caregiving family members, and these
emotional responses affect the reactions of the bipolar family
member and ultimately the course
of the illness. As in other disorders, high expressed emotion
(EE) attitudes (high levels of criticism,
presence of hostility, or high levels of emotional
overinvolvement) in parents of patients with
BD are associated with higher rates of recurrence and more
severe symptoms compared with
low EE attitudes in parents (Miklowitz, 2007).

504 Journal of Clinical Psychology: In Session, May 2012
Figure 1. Developmental pathways to improvement versus
adverse outcomes among youth at risk for
bipolar disorder.
Note. BD-NOS = bipolar disorder, not otherwise specified;
MDD = major depressive disorder; EE =
expressed emotion.
High-EE attitudes among parents of bipolar offspring may have
their roots in childhood
dyadic interactions. As shown in Figure 1, people who later
develop BD, especially those who
grow up with a parent with BD I or II, were often irritable,
aggressive, and emotionally reactive as
children, and they may have been paired with parents with
whom there was a poor temperamental
fit. The caregiving parent may or may not have the disorder, but
usually finds it increasingly
difficult to deal with the child’s temper outbursts, inability to
self-soothe, violence, poor school
performance, and low social competence. Even though these
childhood features may reflect the
early expression of a genetic vulnerability, the dyadic
interactions between parents and the at-risk
child may become increasingly negative over time, especially as
the child reaches adolescence
and strives for more autonomy. When he or she first develops
mood disorder symptoms, or even
difficulty with emotional self-regulation, the stage has been set
for increasingly volatile family
interactions that contribute to the onset and subsequent cyclic
course of BD.
We postulate a similar bidirectional relationship between

parental EE and patients’ bipo-
lar mood symptoms after the onset of the illness (Miklowitz,
2007). The pathway begins
with postepisode residual symptoms in the patient, such as
depression, withdrawal, impul-
siveness, low functioning, or irritability, all of which contribute
to the intensity of the pa-
tient’s reactions to caregivers who are attempting to help the
patient manage the illness. Es-
calating negative family interactions reduce the threshold for
caregivers to react with fear,
frustration, and hopelessness; recall and exaggerate negative
experiences from prior illness
episodes; and make attributions of controllability and negative
predictions about the future
(e.g., ‘‘He’s doing this to hurt me’’; ‘‘I’ll always have to take
care of her”). This cogni-
tive reactivity of the parent may fuel his or her expression of
high-EE attitudes toward the
patient, which creates an aversive, stressful environment for the
patient and contributes to
temporary exacerbations of mood symptoms and a worsening
pattern of dyadic interaction.
In combination with biological and genetic vulnerability
factors, repeated exposure to neg-
ative family interactions may contribute to the patient’s overall
liability to new episodes or
recurrences.
As indicated in Figure 1, the optimal time to intervene in these
processes may be when a
child is showing early signs of the disorder. Typically, this

means that the child has only had
one or two episodes of mania or, more frequently, has had
depression and several brief periods
of mania or hypomania that are impairing or at least noticeable
to others but do not meet the
duration criteria for full episodes. Intervening before the onset
of the disorder or even after the
first or second episode may reduce the frequency of subsequent
episodes and their severity.
FFT assists the parents, child, and available siblings in how to
identify early warning signs
of new episodes and develop strategies for preventing the
episode or limiting its effects on
functioning (psychoeducation). It also includes skill training to
improve day-to-day interactions
and solve problems in the current family environment. These
skill-based components may lead
to the greater use of emotion regulation strategies in the patient.
To encourage acceptance of the disorder and foster effective
emotional communication,
clinicians administering FFT must adopt a psychotherapeutic
attitude, a sensitivity to underlying
emotional conflicts. This aspect of treatment was apparent to us
from the beginning, when
we discovered that the rule-governed, skill-training tasks
typical of behavioral treatments for
schizophrenia were unwelcome to bipolar patients and their
families. Interactions in these
families were highly emotionally charged and members seemed
to thrive on chaos, humor, and
unpredictability. Early on, we hypothesized that highly
emotional family interactions, especially
when members were discussing seemingly minor problems,
signaled underlying conflicts that

needed to be brought into the open and discussed. This case
below illustrates a family with one
such emotional conflict: anger about paternal neglect in
childhood.
To address these family processes, we have incorporated several
structural therapy strategies
(Minuchin & Fishman, 1981) into FFT, such as strengthening
the alliances between the child
and the more disengaged parent or emphasizing the boundaries
between the parental and child
subsystems. We also incorporate the use of reframing and
relabeling. For example, we often label
the aversive behavior of the child as uncontrollable when
parents believe it to be controllable, or
the high level of parent-offspring conflict as normative when a
close relationship is disrupted by
the challenges of the postepisode recovery period.
The version of FFT used in the case illustration also reflected
adaptations suggested by our
colleague, Ben Goldstein, M.D., of the University of Toronto,
who has re-manualized FFT
for dual-diagnoses adolescents with BD (Goldstein et al., 2008).
The goals of the FFT-SUD
approach are as follows: (a) promoting substance-free homes in
which drug or alcohol use by
parents is addressed as a risk factor; (b) challenging the notion
that substance abuse in BD is
self-medication and framing it instead as a health-compromising
behavior; and (c) using problem
solving to identify high-risk situations in which the adolescent
may be exposed to substances
and develop strategies for avoiding these situations or managing
the resulting cravings.

Case Illustration
Presenting Problem and Client Description
Drew, an 18 year old, lived with his mother Angie, age 42,
sister Maddy, 20, and older brother
Daniel, 22, in a suburban, middle-class community. He was
referred to a pediatric mood disorders
clinic for severe drug abuse that his therapist had said might be
masking BD. The original referral,
made just as the school year was ending, requested only a
diagnostic evaluation, although the
family made it clear from the outset that they wanted treatment.
In the prior 3 months, Drew had
been on “lockdown” at his mother’s house pending verification
of several months of sobriety, as
revealed by home-based urinary assays. The event that
stimulated the referral was a relapse of his
marijuana use and increased verbalization of suicidal thoughts.
His biological father Aaron, age
42, was a musician and lighting specialist who lived in another
city and was only intermittently
involved in his life. Aaron attended the intake sessions.
In separate individual interviews, Drew and his parents
described a highly destructive pat-
tern of drug abuse involving oxycontin, cocaine,
methamphetamine, and marijuana. He began
smoking marijuana and using methamphetamine at age 14,
although his worst patterns of drug
abuse had occurred in the year prior to intake. Before his
lockdown, he had been disappearing

late at night to look for fixes; his urinary drug screens were
consistently positive for opiates and
marijuana.
Drew presented as an insightful and agreeable but depressed and
tearful young man. He
mourned the damage he had done to his life and expressed
shame and guilt for hurting his
mother, father, and siblings. His parents agreed that Drew had
always been moody, but that
his moodiness had been much worse in the past 6 months. He
had received minimal treatment.
Individual sessions with a psychotherapist at a city clinic, he
said, had been “OK, helpful at
times.” He had attended a few Narcotics Anonymous meetings
but complained that he could
not relate to them; no one was his age and “the ‘addiction is an
illness’ thing doesn’t really fit
me.” He had never taken a psychiatric medication.
The diagnostic assessment included the Kiddie-Schedule for
Affective Disorders and
Schizophrenia-Present and Lifetime Version (KSADS-PL),
administered by a psychologist and
social worker that separately interviewed Drew and each of his
parents. Drew described a 6-
month period of depression that had begun the previous fall and
included intensely sad mood,
social withdrawal, suicide preoccupations, fatigue,
hypersomnia, loss of appetite, and feelings of
worthlessness. During the majority of this interval, he had been
using marijuana but no harder
drugs. According to his mother, his mood and energy level had
shifted in the spring, during which
he experienced a 1-month period of high mood, rapid thinking

and speech, increased energy,
decreased need for sleep, and grandiose thinking (consumed
with plans concerning elaborate
money-making schemes for nuclear waste storage). He
acknowledged this manic period as out
of the ordinary for him and denied taking any drugs at first,
although he had begun taking
benzodiazepines (obtained on the street) after going several
weeks with minimal sleep. After
multiple truancies during this period, he was expelled from
school in the second semester of his
junior year and began a home-schooling program.
A pharmacological evaluation by a staff psychiatrist revealed a
similar clinical picture, al-
though the psychiatrist was particularly struck by his current
level of depression, which did
not appear related to any drug abuse. His urine toxicology
screen came out negative on the
day of the interview. The psychiatrist agreed that the manic
episode in the spring did not ap-
pear to be precipitated by drugs, although it may have been
worsened by his subsequent drug
abuse.
Drew’s father felt that many of Drew’s problems stemmed from
his relationship with his
girlfriend, Vida, a Latino young woman 3 years older than him.
Vida had her own problems
with drugs and alcohol and came from a small, fractured, inner-
city family. Angie, Drew’s
mother, was less convinced of Vida’s role, and was more prone
to blaming his biological father
for not being accessible enough. Drew agreed that his father had
been inaccessible but did not
feel this was related to his drug abuse or mood swings. When

asked if he thought he had bipolar
disorder, Drew shrugged and said “Probably. Doesn’t
everybody?”
Aaron warily described Drew’s relationship with his mother as
“close but full of tension.”
Angie, who had recently closed her jewelry business and was
pursuing a career in real estate,
acknowledged that she’d felt less effective as a parent of late.
She described Drew’s father as
being “helpful but distant . . . he always keeps Drew at arm’s
length.” Aaron agreed with this
characterization: He had put his emphasis in recent years on his
new marriage and his musical
career.
In the separate interviews, Aaron described his own history of
bipolar I disorder, marked by
repeated and lengthy periods of depression and intermittent
periods of mania or hypomania,
usually sparked by new musical interests and often involved
buying, repairing, and attempting to
re-sell expensive instruments. Surprisingly, he was being
treated only with Effexor, an antidepres-
sant, without a mood stabilizer. He admitted having had
problems with marijuana in the past,
which he said was “part and parcel of being a musician,”
although he denied consistent drug
and alcohol abuse. Angie described herself as having periods of
severe depression alternating
with long-term periods of dysthymia.
Drew’s brother and sister seemed quite protective of him.
Daniel said that his parents had
“turned a blind eye” to Drew’s increasing drug abuse, and that
he had talked to Drew about it

on a number of occasions, to little effect. His sister Maddy, who
had herself been arrested twice
for marijuana possession, saw Drew as “trying hard to fool
himself.”
Case Formulation
Drew received two diagnoses based in part on the KSADS-PL:
bipolar I disorder (currently
depressed) and polysubstance dependence disorder. The
rationale for the bipolar diagnosis was
that he had had both a full manic and a depressive episode in
the absence of significant drug
abuse; he also described periods of depression during his teen
and preteen years, even when
he wasn’t using hard drugs. Although it is possible that these
episodes were accompanied by
substance abuse to which he was not admitting, it is unlikely
that they would have lasted as long
as they did (in the most recent depressive episode, 6 months).
The initial case formulation took account of both biological and
psychosocial factors. Drew
had a strong genetic loading for mood disorder and substance
abuse on both sides of the family.
The family dynamics associated with Drew’s problems became
an early focus of treatment. The
clinicians observed that neither parent seemed clear on what BD
was, although they had both
read about it. Understandably, neither Drew nor his parents
knew how depressive and manic
episodes were different, how to recognize the escalation of new

episodes, or what treatments were
available to them. More salient was the enmeshed relationship
between Drew and his mother
and his stated desire to become closer to his father.
An initial hypothesis was that he was abusing drugs to distance
himself from his mother.
An alternative hypothesis, not mutually exclusive, was the
possibility that his drug abuse and
depression brought him in closer contact with his biological
father who, in his mother’s words,
“always swooped in to clean up a mess, and then swooped out
again.” Drew’s history was rife
with examples of problems that had caused his father to
immediately come to his aid, after which
Aaron disappeared again.
The clinicians offered the family a course of FFT (weekly and
then biweekly), with the stated
goal of helping Drew stay substance-free, maintain a stable
mood, and finish high school. His
psychiatrist recommended a course of lithium, with a target
dosage of 1500 mg. The treatment
regimen also required regular serum lithium assays and urinary
toxicology screens to supplement
those being conducted at home.
Course of Treatment
In the beginning of FFT, the two clinicians scheduled dyadic
sessions separately with Drew and
his mother and with Drew and his father. The initial goal was
similar in both dyads: to educate
the family about BD and substance abuse and develop a relapse
prevention plan. Each dyad
developed a list of Drew’s symptoms of depression (becoming

more socially withdrawn, letting
his appearance go, and looking “angry, lonely and tired”),
mania (decreased need for sleep, an
“electric feeling” throughout his body, more conflict with
family members), and substance abuse
(being “glib” about how he was spending his time, “talking
‘round and ‘round about things,”
impulsive laughter, and behaving like a “caged animal”
[mother’s words]). They were asked to
identify which of these symptoms appeared in muted form
before the onset of a full episode. For
example, irritability appeared to presage the onset of his major
depressive episode, and behaving
like a caged animal antedated an increase in his marijuana use.
In the second step of relapse prevention planning, they
developed a list of potential psychoso-
cial triggers (conflicts with his brother Daniel, excessive
contact with Vida, feeling “boxed in”
by his mother, contact with certain friends with whom he had
used drugs before). In the third
step, they listed a series of prevention and health-promoting
strategies when early warning signs
and triggers were present (talking over his distressed feelings
with his father, talking to Vida by
phone, getting his lithium level tested, arranging an emergency
therapy session, using relaxation
techniques he had learned previously). Drew’s primary concern
in these sessions was getting his
parents to clarify when and under what conditions they would
take him off lockdown and allow
him out of the house. Neither parent was willing to offer such
clarifications.
During the father-son sessions, Aaron was encouraged to share
as much of his own history

as he could with Drew, including how he had coped with his
own mood disorder and intermit-
tent substance abuse. Drew was instructed in active listening, a
communication skill involving
nonverbal attentiveness, asking clarifying questions, and
paraphrasing.
Drew met his own diagnosis and the associated
psychoeducational material with relative
equanimity, saying it explained a lot. He felt validated by his
father’s admission of his own
disorder. He began to read online about BD and was intrigued
by how neural circuits worked
and how medications might alter preexisting neural imbalances.
The clinicians explained the
ways in which BD and substance abuse can negatively interact,
and the importance of keeping
a substance-free home. Indeed, Drew and his father bonded in
educating each other about the
disorder and discussing their individual problems with
substance use, including how to avoid
situations that would lead to use (e.g., parties, certain friends’
houses) and how to manage
cravings (e.g., distraction to delay automatic responses). This
increased understanding was
accompanied by spending more time together, often doing low-
key manual projects (e.g., building
musical instruments, fixing sprinkler systems).
About five sessions into the FFT, Drew requested that the
sessions be focused exclusively
on his relationship with his father. Although his mother and he

had developed a useful relapse
prevention plan and had begun practicing the communication
skills with one another, he felt that
those sessions had taken on a stereotypical quality, in which his
mother lectured him on what it
would take to trust him again, and he gave her hollow
assurances. In his words, the sessions were
“like hearing the same joke over and over again.” The clinicians
decided to honor his request,
and his mother, who felt that Drew would be hurt by returning
to the distant relationship he
used to have with his father, agreed.
After a brief period of communication enhancement training for
Drew and his father, the two
began to spontaneously discuss their relationship, especially
events from the past. The clinicians
had reached a decision point: Should they continue with skill
training in the step-by-step fashion
outlined in the FFT protocol, or depart from the protocol to
address historical events and the
associated feelings? Their decision to do the latter reflected two
conclusions. First, Drew seemed
stable enough to tackle more personal conflicts and seemed to
want to do so. Second, neither
member of the dyad was likely to adopt the new communication
skills until these issues were
addressed.
Drew held considerable resentment toward Aaron for having
“abandoned” [his words] the
family when Drew was 6 years old. Aaron’s response was
apologetic, but he also used the
opportunity to clarify how complex his life had been early on.
As he described it to Drew in a
communication exercise, he had been “young, dumb, 25 years

old with no job, three kids, and a
failing marriage.” At the time, he believed that separating from
the family and giving his ex-wife
maximal control over the children was better for them, given
how confused he felt about his
own future. Drew and his father spent several sessions
discussing events from Drew’s childhood
and early adolescence. His sister and older brother attended
several of these sessions and seemed
equally motivated to discuss key events in the family’s history.
Although anger and tears were
often generated by these discussions, all agreed that the format
allowed them to talk about things
they had never discussed before.
About 3 months into treatment, Drew got an afternoon and
weekend job at a dairy farm,
which got him out of the house and gave him plenty of exercise.
His mood gradually improved
and he became euthymic by the Christmas holidays. Throughout
the fall, his urinalyses were
consistently negative, and his lithium levels were within the
therapeutic range. He complained
of lithium’s side effects, including increased urination, a hand
tremor, and a blunting of his
emotions. He did admit, however, that his mood felt more
stable. He remained adherent to
treatment, completed a home-schooling curriculum, and did
quite well despite taking demanding
math and science classes.
Increasingly, Drew wondered whether his prior drug abuse
reflected “self-medication” of his
depressive and manic symptoms. This possibility, he felt, was
bolstered by his positive response
to lithium, which had reduced his cravings significantly. The

clinicians warned against this view,
noting that substance use is likely to aggravate rather than
control mood swings and often
temporally precedes mood disorder recurrences (Strakowski,
Delbello, Fleck, & Arndt, 2000).
Nonetheless, as the treatment transitioned into the problem-
solving phase at approximately
6 months, it was easy for everyone, including the clinicians, to
believe that Drew’s drug abuse
and mood swings were now a thing of the past.
Relapse. After the holidays, and after a 2-week break from FFT,
Drew’s mother decided
to resume his urine assays because “his behavior was getting
strange again.” She had lifted the
lockdown approximately 3 months earlier, under the condition
that he stay sober and continue
to take his lithium. His first urine assay came back positive for
marijuana and opiates. His
psychiatrist checked his lithium level, which was 0.4 mmol/L,
well below the therapeutic level.
During a family session which included Drew, his parents, and
both siblings, he admitted that he
had been gradually cutting back on the lithium over the prior
month and was now down to one
300 mg pill per day. His mood and behavior were mildly
hypomanic, with increased irritability
and decreased sleep over the prior 2 weeks; his thinking had
taken on a grandiose quality. He
had continued working and completed his fall school
assignments, although with difficulty.

Drew explained that he did not fully believe he had BD, and
that he wanted to test this belief
by going off of his lithium. He wanted to know “what my mind
is capable of without drugs in
my system.” He was less clear on why he had begun smoking
marijuana and using opiates again,
except to say that they relaxed him, made him feel more social,
and made him less combative
with his family. His mother and father were quite upset; his
mother wondered aloud if he needed
residential substance abuse treatment. Daniel, who had held the
view that nothing was wrong
with Drew except stubbornness and immaturity, expressed anger
that “he’s got all of us on a
string.”
The clinicians conducted a behavioral analysis to determine
what sequence of events had led
to Drew’s drug use and lithium discontinuation. They asked him
to recreate the details of his
most recent use, his thoughts and feelings at the time, and the
interpersonal events or stressors
that had precipitated and followed the use. His marijuana use
was largely related to wanting to
reconnect with friends, believing that these friendships
depended on marijuana use. He denied
that his girlfriend Vida had been involved in his decision to use,
and in fact she was quite angry
with him about it.
Drew’s decision to stop the lithium had been brewing for some
time, although it was hastened
by a comment one month earlier from Daniel, who had said in
the heat of an argument, “Your
brain is wired all wrong. Maybe you should take more of that
damn medication.” He rationalized

his decision to stop lithium with, “My mind isn’t working
anymore. Now everything I do feels
like it’s because of the medications I take. I want to clear my
mind of all the toxins I’ve put in
it.”
It is quite common for young patients with BD to test the waters
by discontinuing their
medications. This is part of the natural developmental process
in accepting a long-term ill-
ness. In the vignette below, the clinicians framed Drew’s doubts
about the bipolar diagnosis as
healthy and expectable for his age. They also pointed out the
contradiction between wanting to
have a substance-free mind to determine his capabilities and
also wanting to smoke marijuana
regularly.
Drew : I wouldn’t be surprised if it turned out I didn’t even
have bipolar
disorder.
Clinician : It’s understandable that you’d have that question.
You’ve only had the
one manic and one depressive episode. Most people who’ve just
been
diagnosed have that same question.
Drew : Yeah, and I wonder if I would’ve even had those if I
hadn’t been using
before. I guess I don’t really even know what I’m like. Maybe
without
the lithium I’d know.
Clinician : How would stopping your lithium tell you if you
were bipolar or not?

Drew : Maybe it wouldn’t. But I would like to know what it’s
like to have a
clear head without any drugs in it.
Clinician : I can certainly understand wanting to know that. But
then why would
you want to smoke weed? That’s not a very good test of what
your
mind is like without drugs.
Drew : Good point.
Mother : In fact, it fogs your mind and your feelings even more
than lithium.
Drew (defensive) : No it doesn’t. You don’t know what it’s like
inside my head.
Clinician (redirecting) : Neither do I. But I think your questions
about the bipolar diagnosis are
healthy. It’s good to ask questions before you accept any
diagnosis. But
let me ask you again—how will going off your lithium and
smoking
weed instead tell you whether you’re bipolar or not?
The clinicians pointed out that Drew’s marijuana and oxycontin
use could increase the
likelihood of a manic relapse and, at minimum, would interfere
with any therapeutic effects of
the lithium in his system. They challenged the notion that
marijuana is a medical treatment for

BD. (In fact, the research literature suggests the opposite,
namely, that increased marijuana use
and the worsening of mania symptoms become intertwined with
time; Strakowski et al., 2000.)
Drew responded thoughtfully to these points and agreed to
resume the urinalyses, but made no
further commitments about taking lithium or remaining sober.
Postrelapse course of treatment. It is critical to resume FFT as
soon as possible after
a mood or substance abuse relapse, to communicate that the
treatment’s objectives can still be
achieved despite setbacks. Families are often frustrated at this
point with the recurrent nature
of mood and substance use disorders and are eager to get on
with their own lives. Sometimes,
family members will interpret a relapse as meaning that the
treatment did not work and that
the patient should instead be treated individually. Clinicians in
FFT emphasize that relapses are
an expected part of the course of mood and substance use
disorders. In this case, they pointed
out that Drew’s relapse was less severe than it might have been
without medication and FFT
sessions. Although we sometimes do recommend adjunctive
individual sessions to supplement
family sessions, Drew’s therapists were convinced of the
centrality of family dynamics in the
course of his substance use disorder. In addition, Drew
preferred the family format.
After a session of problem solving, in which the problem of
Drew’s lithium nonadherence
was addressed, Drew reluctantly agreed to go back on his
medication “for a few months.” His
parents reintroduced drug testing, and the FFT sessions, which

had been tapered to biweekly,
resumed at a weekly pace. The clinicians decided to broaden the
sessions to include his siblings
on a more regular basis. One session with his mother and father
also helped clarify rules to be
kept consistent across the two households.
In the family sessions with Drew and his siblings, Aaron began
to share more of his own history
of BD. At the urging of his psychiatrist (who had been in
contact with the FFT clinicians), he
had begun taking divalproex sodium (Depakote), a mood
stabilizer, and felt that his mood was
more stable than it had been in years. He described several prior
manic episodes during which
he had lost jobs, and compared them to Drew’s most recent
relapse. Drew recalled one prior
episode where his father showed up at his mother’s house late
on a school night, asking Drew to
drive out to the desert with him to climb on some wind turbines.
In a session that did not involve his mother, and within the
context of a structured commu-
nication exercise, Drew’s older brother and two sisters
expressed anger at Aaron for his role in
their fractured family life. Maddy felt that she had been
invisible to her father for most of her
life, and that her own drug abuse had been a “cry for help” from
her father. In fact, her arrests
had succeeded in bringing him back into her life for short
periods of time, after which she ex-
perienced feelings of abandonment that led to more drug abuse.
Daniel, never big on emotional
expression, said simply that “It’s like supply and demand . . .
Dad is a limited quantity.”

After listening to his children’s pain, Aaron admitted that
closeness with his children fright-
ened him and made him worry that he was not up to the task of
being a father. He recalled
his feelings of helplessness when his children were born, and he
did not feel he could support
them financially or emotionally. Drew and his siblings were
encouraged to paraphrase their
father’s statements and ask him to clarify any
misunderstandings they had about his role in
family events. In the end of this segment of treatment, the
clinicians praised the young adults for
their courage in confronting their feelings about Aaron, and
Aaron for his openness to hearing
his children’s painful recollections. They reframed Drew’s
recent relapse as having served the
purpose of bringing these elements of the family’s history into
focus.
In sessions with his mother, the clinicians encouraged Drew to
examine his own role in their
enmeshed relationship. He fought her protectiveness with angry,
somewhat childish attempts
at independence (smoking marijuana in his room with the
window open and leaving the house
and not telling her where he was going). The clinicians made
clear the bidirectional, reciprocal
relationship between these actions, his mother’s response,
Drew’s attempts to further establish
his independence, and her attempts to control the situation
further. They rehearsed with Drew

several response styles that might alter these predictable
interaction patterns. For example, Drew
role-played with his mother how he might reassure her
regarding his whereabouts and how she
might respond if she wasn’t satisfied. A single session with
Drew and Daniel helped develop a
common perception of what Drew’s bipolar disorder was and
wasn’t and how to understand the
causes of his substance abuse.
Toward the end of treatment, the clinicians encouraged Drew to
integrate Vida into his
growing relationship with his father. Aaron and Vida had never
trusted each other, yet both
realized they would have to forge a connection to keep Drew
from compartmentalizing his life
with Vida. Eventually, Drew and Vida invited Aaron and his
wife to have dinner with them. The
evening was not cozy but proved to be an important first step in
bridging important gaps within
this family.
Outcome and Prognosis
At a follow-up session one year after intake, Drew had
discontinued his lithium but also had
stopped smoking marijuana and showed no evidence of other
drugs on his toxicology screens.
His mood had been stable for 3 months, and he had retained his
job at the dairy farm. He finished
high school and was taking classes at a local community
college. His relationship with his father
had become closer, and with his mother, brother and sister,
more civil. In the final session, the
clinicians reminded Drew and Aaron that their relationship
needed ongoing maintenance, much

like the musical instruments they had built together. They used
the problem-solving format to
plan at least one casual contact per week during the upcoming
school year.
Clinical Practices and Summary
Although the basic structure of FFT—psychoeducation,
communication training, and problem
solving—was retained in Drew’s case, the clinicians went well
beyond the manual to include
elements of structural family therapy. In particular, they
concentrated on the restructuring of
alliances, such that Drew’s enmeshed, interdependent processes
with his mother were interrupted,
and his tenuous, disengaged relationship with his father was
bolstered. To accomplish these goals,
painful events from the past (notably, Drew’s and his siblings’
resentments of their father’s limited
role in their upbringing) were discussed within the format
provided by communication training.
Structural interventions may be especially relevant when
treating children in divorced families
in which disruptions to healthy patterns of intergenerational
alliance (e.g., connections between
a biological father and his children) contribute to a child’s
presenting problems.
Had Drew been in a controlled study, the clinicians would have
had less flexibility in structuring
the sessions and would have been discouraged from
emphasizing active listening to the neglect of
other communication skills such as positive requests for change
or offering positive feedback. The
problem solving tended to focus on larger problems such as how
to maximize contact between

Drew and his father, rather than daily hassles that might have
been more easily solved (e.g.,
his mother’s complaints about his cleanliness). Departures from
a treatment manual are more
problematic in controlled research studies than in actual
practice, especially if they occur more
in one treatment than another. We do not know whether
departures from the FFT manual have
a negative effect on the prognosis of patients, or whether the
complexity of certain patients or
family situations requires such departures.
We have been continually impressed, however, that departing
from the skill-training agenda to
focus on the history of conflicts between people, interrupting
enmeshed relationships in certain
dyads and encouraging alliances in others, or strengthening
boundaries between individuals or
subsystems can often unlock a family’s resistances to learning
new skills or incorporating illness-
related coping strategies. The clinician must decide early on
whether the patient is stable enough
to address problematic relational processes or interactional
patterns or whether addressing them
should occur later, once the patient has recovered and is capable
of handling high emotional
intensity. The key, as it is in other evidence-based treatments, is
to balance fidelity (to the
treatment manual) with fit (to the particular circumstances and
family).

Assessing and treating mood disorders in individuals with substance abuse

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