Bipolar and Substance Use Disorder

8 S E P T E M B E R 2 0 1 8P S Y C H I AT R I C T I M E S w w w . p s y c h i a t r i c t i m e s . c o m CLINICAL

» Ming Ma, Alexandria S. Coles, and Tony P. George, MD

Ms Ma is an undergraduate student in psychology at the University of Toronto; Ms Coles is research coordi- nation in the Biobehavioral Addictions and Mental

Health Laboratory, Addictions Division, Centre for

Addiction and Mental Health; Dr George is Professor, Department of Psychiatry, University of Toronto and

Chief, Addictions Division, Centre for Addiction and

Mental Health.

B ipolar disorder is a disabling psychiatric disor-

der that presents in approximately 1.5% to

2.5% of the population.1 It is characterized by

mood instability (hypomania/mania), depression, or

mixed manic and depressive episodes. Fluctuations

in mood are frequently accompanied by changes in

energy levels and sleep patterns.

Substance use disorders (SUDs) are common

among individuals with BD. Findings from a large

meta-analysis indicate that the lifetime prevalence of

alcohol and cannabis use disorders in BD is 42% and

20%, respectively.2 The lifetime prevalence of tobac-

co smoking in BD is as high as 60% to 80% compared

with approximately 15% in the general US popula-

tion.3,4 Co-occurring substance use is associated with

earlier illness onset, suicidality, rapid cycling and

mixed features, and more severe symptoms.5-7 Fur-

thermore, there can be serious societal and economic

consequences, including higher rates of violence,

crime, homelessness, and health care costs. A better

understanding of this comorbidity is important for

diagnosing and treating these dual diagnosis patients.

CASE VIGNETTE

John is a 22-year-old white single male with a history of

bipolar I disorder. He was a student at a local communi-

ty college until a month ago when he dropped out

abruptly. Since age 16, he has been taking valproate

sodium (1000 mg daily) and sertraline (100 mg daily),

but he is only partially responsive to these medications

(frequent mood instability, currently experiencing de-

pressed mood). Over the past year, he admits to regular-

ly drinking beer (3-4 times per week, 2-3 standard

drinks per session). Although he rarely drinks to intoxi-

cation, his parents and friends consider him increasing-

ly unreliable. He has also been smoking cannabis and

crack cocaine in the past 6 weeks and says that he has

“never felt better.” He thinks that he has no real drug

problems and regards drinking as his way of coping.

Possible explanations for co-occurring BD and SUDs A bidirectional relationship exists between BD and

SUDs. Compared with individuals without psychi-

atric disorders, those with bipolar illness may be

more vulnerable to initiating substance use; moreo-

ver, chronic substance users may be at greater risk of

mood disorders than non-substance users.6 Although

the exact mechanism underlying these co-occurring

disorders remains largely unclear, several different

explanations have been offered.

First, there appear to be genetic associations be-

tween BD and SUDs. A recent study estimated that

47% to 57% of the genetic variance in bipolar illness

predisposition is linked to alcohol use disorder,

which supports the idea that the two disorders may

be genetically correlated.8

Second, BD and SUDs share common neurobio-

logical pathways, and behavioral sensitization (eg,

“kindling”) may be a common mechanism. Repeat-

ed exposure to alcohol and drugs sensitizes neurons

and is associated with increasingly rewarding ef-

fects. Interestingly, the course of BD follows a sim-

ilar pattern (ie, episode sensitization). Therefore,

individuals with a tendency to sensitization may be

at greater risk of developing both bipolar illness and

SUDs. This has led to the proposal that co-occurring

BD and SUDs may respond better to anticonvulsant

mood-stabilizers rather than lithium.6

Third, certain traits associated with BD may ele-

vate the risk for patients to engage in substance use.9

These include impulsivity, poor coping strategies for

stress, and excessive pleasure-seeking associated

with the manic or hypomanic phases of the illness.

These findings are compatible with the hypothesis

of addiction vulnerability in patients with psychiat-

ric disorders.10

An alternative explanation for co-occurring BD

and SUDs is the self-medication hypothesis, which

proposes that patients use substances to help allevi-

ate BD symptoms. Empirical evidence regarding

this hypothesis is mixed. Notably, mood symptom

improvement is generally observed once abstinence

is initiated, which is inconsistent with the self-med-

ication hypothesis of SUDs in bipolar illness.11

Assessing and diagnosing co-occurring BD and SUDs Assessment and diagnosis of patients with co-occur-

ring BD and SUDs can be challenging for a number

of reasons. First, bipolar illness itself is a heteroge-

neous disorder with different subtypes and presenta-

tions. In fact, it is not uncommon for it to be misdi-

agnosed as unipolar depression.

Second, symptoms of alcohol and drug intoxica-

tion and withdrawal may resemble BD symptoms,

making it often difficult to distinguish between the

two. For instance, acute administration of central

nervous system stimulants such as cocaine and am-

phetamines can lead to euphoria and increased ener-

gy, which overlap with symptoms of mania and hy-

pomania.

Alternatively, misuse of alcohol and benzodiaze-

pines can mimic depressive symptoms. Symptoms

of withdrawal (eg, depression, dysphoria, sleep dif-

ficulties) also parallel BD symptoms in the de-

pressed or mixed phases. Moreover, there is some

evidence that BD comorbid with SUDs more com-

monly presents clinically with rapid cycling (eg, > 3

cycles per year between mania and depression) and

mixed (dysphoric) manic features, which further

complicates the diagnostic process.

Integrated treatment for co-occurring BD and SUDs Diagnosis is the first challenge in the care of patients

with co-occurring bipolar illness and SUDs; finding

effective treatment is arguably just as challenging.

Although there is no one single optimal treatment

strategy, the management of these co-occurring dis-

orders should integrate both pharmacological and

psychosocial interventions.

A number of different pharmacotherapies have

been efficacious in treating co-occurring BD and

SUDs. In early studies, lithium was found to im-

prove BD symptoms and reduce levels of substance

use.12 Valproate has also been found to be effective

at improving affective symptoms, decreasing sub-

stance craving, and reducing alcohol and drug

use.13,14 Compared with valproate, lithium is associ-

ated with lower suicide risk during treatment, but it

may be less effective in treating bipolar illness asso-

ciated with SUDs.15

A number of studies have examined quetiapine in

treating patients with co-occurring disorders. While

quetiapine may reduce depressive symptoms, it did

not reduce alcohol use.16 Findings indicate that lamo-

trigine and topiramate are not particularly useful in

treating comorbid bipolar illness and SUDs.15,17 Thus,

while the use of anticonvulsant mood stabilizers and

second generation antipsychotics for co-occurring

bipolar disorder and SUDs is an attractive concept

and may have some clinical utility, further research to

substantiate these observations is warranted.

In addition to mood-stabilizing agents, adjunc-

tive addiction pharmacotherapies should also be

considered in treating dual diagnosis patients. Nal-

trexone has been shown to significantly reduce both

manic and depressive symptom severity and de-

crease alcohol use in patients with bipolar disorder

and alcohol dependence.18

Psychotherapy should also be included in the

treatment plan to support pharmacotherapies. Psy-

chosocial interventions are important for addressing

issues such as diagnosis acceptance, treatment com-

pliance, and relapse prevention. Integrated group

therapy, for instance, has been shown to be effective

at reducing drug problem severity, encouraging ab-

stinence, and decreasing the risk of mood episodes.19

This type of group therapy typically consists of five

to eight patients for approximately 20 weekly ses-

Understanding and Treating Co-Occurring Bipolar Disorder and Substance Use Disorders

Treatment should integrate pharmacotherapy (eg, mood stabilizers, adjunctive addiction medication) and psychotherapy (eg, integrated group therapy, CBT, psychoeducation, MI).

S E P T E M B E R 2 0 1 8 9P S Y C H I AT R I C T I M E S w w w . p s y c h i a t r i c t i m e s . c o mCLINICAL

sions, and focuses on themes common to both

BD and SUDs, such as identifying and deal-

ing with triggers.

Cognitive behavioral therapy (CBT), which

involves identifying and changing biased

thoughts and beliefs, also shows promise in the

treatment of co-occurring BD and SUDs. Pa-

tients who received CBT treatment had re-

duced symptom severity, decreased substance

use, and longer abstinence periods.20

Psychoeducation is effective at improving

mood symptoms and reducing relapse in pa-

tients with bipolar illness. Because it enables

patients to develop a more objective under-

standing of the disorder and learn strategies to

manage mood symptoms, it should also be

suitable for individuals with co-occurring dis-

orders. Finally, motivational interviewing (MI)

should be used to engage patients with co-oc-

curring BD and SUDs into initial treatment.

Conclusions Co-occurring bipolar illness and SUDs are

associated with adverse clinical, social, and

economic consequences. They are not only

difficult to diagnose, but are linked to in-

creased symptom severity, poorer treatment

outcomes, and greater suicide risk. Treatment

should integrate pharmacotherapy (mood sta-

bilizers and adjunctive addiction medication)

and psychotherapy (integrated group therapy,

CBT, psychoeducation, MI).

Neuromodulation methods such as repeti-

tive transcranial magnetic stimulation (rTMS)

and transcranial direct current stimulation

(tDCS) have shown promise in treating mood

disorders and SUDs.21 While many challeng-

es remain in the accurate and timely assess-

ment and treatment of patients with co-occur-

ring BD and SUDs, considerable progress

has been made towards improving the care of

these complex patients.

More research into this important area,

particularly on clinical differences in bipolar

illness with and without SUDs, and on match-

ing treatments to SUD comorbidity (eg, phar-

macological, behavioral), is needed if we are

to make further improvements in treatment

outcomes and quality of life for patients.

ACKNOWLEDGMENTS—This work is supported in part by

NIDA grant R21-DA-043949 to Dr George.

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