2011 ICBD Conference - Practical Applications of New Research in Bipolar Disorder

8/2/2019 2011 ICBD Conference - Practical Applications of New Research in Bipolar Disorder

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2011 ICBD Conference Coverage: Practical

Applications of New Research in Bipolar

Disorder

Paul King, MD (Series Editor)

Medical Director, Parkwood Behavioral Health System, Olive Branch, Mississippi

Bipolar disorder is a leading cause of disability worldwide,1

and the lifetime prevalence

of this condition is about 1% in community populations.2

This activity presents

highlights from 4 presentations given at the 2011 International Conference on Bipolar

Disorder (ICBD), a conference dedicated to sharing research results and clinical

experience to help clinicians improve the lives of those with bipolar disorder.

Medical Lifestyle Management: Theory and

Interventions

Patients with bipolar disorder and metabolic syndrome have more manic and depressive

episodes, longer duration of depressive episodes, more psychiatric hospitalizations and

suicide attempts, higher medical costs, and greater symptom severity and functional

impairment.3

Despite the high prevalence, burden, and dire consequences of metabolic

disorders in bipolar disorder, these conditions remain underrecognized and undertreated.

AV 1. Barriers to Implementing Guideline-Concordant Medical Monitoring in Mental

Health Care (00:23)
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Cardiometabolic conditions. Most deaths in bipolar disorder occur from natural causes,

with the most frequent being cardiovascular mortality.4

In fact, patients with bipolar

disorder are likely to have cardiovascular disease 5 times as often and almost 15 years

earlier than their healthy counterparts.5

Even in pediatric bipolar disorder, youths have

excessive obesity, hypertension, and diabetes, as well as an increased metabolic

sensitivity to mood stabilizers.6

Even though cardiometabolic conditions are common

and can be fatal, many mental health care providers do not implement guideline-

concordant care with respect to medical monitoring (AV 1AV 1).7

The risk for cardiometabolic conditions is increased in mood disorders for several

reasons, and patients with bipolar disorder often have multiple risk factors. Medical

factors, such as inflammation, genetics, poor circulation, diabetes, and hormonal
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dysregulation, as well as modifiable lifestyle factors, such as being overweight or obese,

smoking, and having poor dietary and exercise habits, substantially contribute to

cardiovascular risk.811

Medications to treat bipolar disorder can also contribute to an

increased risk of cardiovascular disease and metabolic disorders.

When clinicians provide comprehensive care, patients with bipolar disorder experiencenot only improvement in mental and physical status, but also a reduction in risk of

cardiovascular events, more attention from healthcare providers, an improved quality of

life, and a greater satisfaction with care.12,13

Implementing a bipolar disorder medical

care model such as that provided by Kilbourne et al14

establishes a framework for

physicians to provide quality, comprehensive care.

Health benefits of sleep. Sleep disturbance is a cardinal symptom of bipolar disorder

and leads to inadequate recovery and relapse risk.15

Patients with mania have a

decreased need for sleep, while those with depression often have insomnia or

hypersomnia.16

As with cardiovascular disease, obesity, poor diet, and lack of exercise

negatively impact sleep hygiene.11,17,18 To improve sleep for patients with bipolardisorder, the presenters stated that clinicians can combine principles from CBT for

insomnia, interpersonal and social rhythms therapy, and chronotherapy.1921

Real-time interventions. Bipolar disorder has a tremendous medical illness burden and

high mortality rates associated with poor lifestyle choices, including smoking, substance

use, and obesity. The presenters stated that, from the outset of treatment, clinicians

should be aware of these common health risks in patients with bipolar disorder and

implement interventions to effectively address them.

Unfortunately, many barriers exist that impede successful smoking cessation, including

a lack of provider buy-in and insurance reimbursement, long-standing attitudes about

smoking in the mentally ill, and the lack of awareness of available resources.

Additionally, barriers to successful behavioral changes to reduce cardiac risks include

misconceptions about medical treatments, lack of integrated mental and medical health

care, and lack of treatment by nonspecialty physicians. Also, in a misguided effort to

promote a good quality of life, caregivers and family members may resist healthful

interventions and enable their loved ones to continue unhealthy behaviors.

To overcome these barriers and help patients lead healthy lifestyles, the presenters

recommended that clinicians systematically identify risk factors, educate patients about

the hazardous effects of an unhealthy lifestyle, and implement interventions to promotehealthy behaviors such as quitting smoking, eating healthy foods, and managing weight

gain. Further, motivational interviewing, CBT, and pharmacotherapy are specific

therapies that can aid patients in leading healthier lives.

For clinical use. Integrated management of psychiatric and medical care is necessary to

help ensure optimal outcomes for patients. Based on the presentations, the following

recommendations were made for clinicians to use in their practice:

Screen patients with bipolar disorder for metabolic abnormalities, including diabetes, dyslipidemia, andhypertension

Complete a risk/benefit assessment of treatment for each patient and then tailor appropriate therapies to thatpatient

Educate patients about bipolar disorder and the common co-occurrence of medical illnesses


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Systematically identify risk factors and address unhealthy behaviors, including poor sleep hygiene,smoking, poor diet, and lack of exercise

Bipolar Disorder and theDSM

TheDSMis currently being updated, and the fifth edition is slated to be published in2013. In revising the currentDSMcriteria, the goals were to:

Clearly differentiate between psychiatric disorders to be as useful as possible to clinicians duringassessment and treatment

Be evidence-based and provide a foundation for future research Consider comorbidities that may affect treatment Be easy to use, clinically applicable, and valid across disciplines Preserve the continuity achieved with the other versions of theDSMwhile having no a priori limitations on

the degree of change

When proposing new disorders or retiring disorders, the work groups have been chargedto articulate the reasons and present supporting evidence for the change, as well as

consider the need for the category, the disorders relationship with otherDSMdisorders,

and available treatments for the disorder.

Mixed episodes. To meet theDSM-IVcriteria for a mixed episode, both the manic

episode and the depressive episode criteria must be met nearly every day for at least 1

week.2

The mood disturbance must cause impairment and must not be due to a

substance or medical condition. These restrictive criteria do not reflect the current use of

the term "mixed," which can cause confusion and inaccuracy, and using these criteria

results in a lack of suicide risk awareness, inappropriate treatment, and unsuccessful

identification of the likelihood of progression from unipolar to bipolar disorder.

AV 2. ProposedDSM-5 Criteria for a Mixed Episode Using a Specifier(00:32)
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To be more consistent with clinical use as well as in the literature, the DSM-5 Mood

Disorders Work Group is revising themixed episode criteria. Using a mixed episode

"specifier" allows for subthreshold symptoms of one pole to be present during a full

episode of the opposite pole; this criteria could be used for both unipolar and bipolar

disorders (AV 2AV 2).22

Validators of the proposed mixed specifier criteria include

having a family history of mixed states, early illness onset, multiple episodes,

suicidality, comorbidities, traumatic brain injuries, poor treatment outcomes, mood

instability, and progressing from unipolar to bipolar disorder.

Hypomanic episodes. To meet theDSM-IVcriteria for a hypomanic episode, criterion A

currently states that a patient must have "a distinct period of persistently elevated,

expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different

from the usual nondepressed mood."2(p368)

When reviewing thiscriterion, the presenters

recommended the addition of "activity or energy." Although inferred in the current

criteria, inserting this language reinforces that increased activity and energy is a cardinal

symptom of mania and hypomania.

The presenters also examined the arbitrary 4-day duration ascribed for a hypomanicepisode, a critical definition for bipolar II disorder and bipolar spectrum disorders,
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which has been a major point of contention. Although some patients have hypomania

that lasts fewer than 4 days, decreasing the 4-day duration criterion would substantially

increase the number of people with bipolar II disorder, and the literature simply does

not support this change at this time. So, those who do not meet criterion A for

hypomania typically fall into the catchall diagnostic category of bipolar disorder NOS.

The problem with this diagnostic entity is that subcategories are not defined, coded, ortrackable. To improve the NOS specificity for each diagnostic group, the presenters

recommended adding the subcategories "subsyndromal," "other specified," and

"unspecified due to insufficient information." Subsyndromal hypomania, then, would

include "short duration" of 2 to 4 days and "insufficient symptoms" qualifiers.

The international BRIDGE study23

used a bipolar specifier (ie, adaptedDSM-IV

criterion A to allow for increased activity for mania and hypomania, and no minimum

duration for hypomania) to assess the occurrence of bipolar disorder in MDD. Of 5,635

patients diagnosed with MDD, 16% met the criteria for bipolar disorder. When the

specifier was used, 47% met the criteria for bipolar disorder (AV 3AV 3). Patients with

bipolar I disorder had higher recurrence rates, suicidality, psychosis, hospitalizations,and family history of mania, while those with bipolar II disorder had higher rates of

comorbid psychiatric disorders. The specifier criteria was more sensitive thanDSM-IV

criteria regarding validators and provided the opportunity for earlier and more accurate

diagnoses.

Changing the NOS category will impact classification codes and insurance billing,

targets for drug development, and clinicians understanding of the bipolar spectrum as

well as research opportunities in bipolar disorder. The rest of the criteria for a

hypomanic episode would remain unchanged.

For clinical use. Clinicians should be aware of potential changes to theDSMcriteria for

bipolar disorder, including:

Using a specifier for mixed episodes that requires either a full manic or depressive episode with eithersubthreshold manic or depressive symptoms

Using a specifier for hypomanic episodes (under the category NOS) to add "activity or energy" as asymptom and to shorten the required duration for symptoms.

Current Status of Child and Adolescent Bipolar

Disorder

Diagnosis. Bipolar disorder is prevalent in youth and commonly has an early age at

onset.24,25

Having bipolar disorder adversely affects the normal development of children

and substantially increases the risk of suicide, substance use, and psychosocial

problems. Further, young patients who have elevated mania, which often results in poor

functioning, severe mood symptoms, disruptive behavior, and anxiety, often do not

meet the diagnostic criteria for bipolar disorder or receive a bipolar disorder NOS

diagnosis.26

AV 4. Developmental Differences in the Clinical Presentation of Bipolar Disorder for Children

and Adolescents (00:21)
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The presenters noted that diagnosing pediatric bipolar disorder is difficult due to

varying clinical presentations, developmental problems, and symptom overlap with

other disorders (AV 4AV 4). Further, even defining the disorder for this population can

prove problematic, eg, irritability versus elation, acute versus chronic course, rapid

cycling, and narrow versus broad criteria. The rates of bipolar diagnoses are rising,

particularly in the United States, which may be due to the use of a broader definition of

the disorder, including NOS.27

In the longitudinal course, children with bipolar disorder

have worse prognoses, more subsyndromal recurrences, and more mood variation

within episodes than adults.28

Further, almost half of youth with bipolar disorder NOS

are likely to convert to bipolar I or bipolar II disorder, and a fourth of those with bipolar

II disorder are likely to convert to bipolar I disorder.28 A main predictor of developingbipolar disorder is having a family history of the condition.

29

Treatment. Several therapies are available to effectively manage bipolar disorder in

children and adolescents. Concerning pharmacotherapy for young patients with bipolar

disorder, divalproex was not shown to be superior over placebo for acute mania30

and

SGAs were more effective than mood stabilizers for acute manic and mixed

episodes.31,32

However, youth are sensitive to metabolic adverse events associated with

some SGAs, including weight gain and increased triglycerides and cholesterol.33

Overall, long-term placebo-controlled studies are needed to further assess medication

efficacy in this population.

For psychotherapy, multifamily psychoeducational psychotherapy plus treatment as

usual has been shown to improve mood for children with mood disorders, including

those with bipolar spectrum disorders.34

Additionally, family-focused therapy has

helped to reduce depressive and manic symptoms in adolescents through moderating

parental expressed emotion.35

For clinical use. Diagnosing and treating bipolar disorder in children and adolescents

can be challenging. To aid in this process, the presenters recommended that clinicians:

Understand the burden and effect of having bipolar disorder for children and adolescents

Recognize the varying presentations of bipolar disorder
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Be aware of the side effect profiles of SGAs and the efficacy of SGAs over mood stabilizers for acute manicand mixed episodes

Consider implementing psychosocial interventions for young patients with bipolar disorderDebates in Bipolar Disorder: Antidepressants Are

Ineffective for Bipolar Depression

AV 5. Agents Initially Prescribed for Bipolar Disorder (0:30)

Antidepressants continue to be the most commonly prescribed class of psychotropic

medications.36

Even in bipolar disorder, antidepressants are prescribed twice as often as

mood stabilizers (AV 5AV 5).37

Although not recommended as a first-line treatment,

the presenters stated that antidepressant agents can have both benefits and harms when

treating bipolar depression; however, evidence of antidepressant efficacy in bipolar

disorder is limited.

Benefit. One benefit may include response to treatment in acute and maintenance

phases, although the evidence is not overwhelming. In the short-term treatment of

bipolar depression, one meta-analysis38

found that, in addition to mood stabilizers or

atypical antipsychotics, antidepressants were more effective than placebo, while anothermeta-analysis

39found a small but insignificant difference favoring antidepressants; both

reported that antidepressants did not increase the risk of manic switch. The presenters

noted that almost all efficacy studies on antidepressants present positive results, but

upon further analysis by the FDA, only about half of those studies are actually

positive.40

In studies41,42

of the long-term treatment of bipolar depression, antidepressants either

alone or with a mood stabilizer did not substantially prevent depressive relapse or

increase a manic switch, reinforcing that mood stabilizers are the mainstay of

prophylactic maintenance treatment. However, in those who achieve remission with an

adjunctive antidepressant, the longer the antidepressant is continued, the less likely it is

to lead to a depressive relapse.43

On the other hand, patients with rapid-cycling may
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have worse outcomes when continuing antidepressants. Other types of depression that

have poor antidepressant response include mixed depression, neurotic depression,

melancholia, and mixed or melancholic bipolar depression.

Harms. Harms of antidepressants in bipolar disorder include inducing a switch to acute

mania, mood destabilization, and suicide risk. Regarding a switch to mania,antidepressants have not been shown to clearly increase this risk,

38,39,44although

switching may be more common in bipolar I than in bipolar II disorder.45,46

Also, using

antidepressants over the long term may lead to treatment refractory bipolar disorder and

mood destabilization, particularly with TCAs, which contribute to rapid cycling.42

For

suicidality, factors such as illness severity and chronicity and age must be considered,

and patients on antidepressant treatment should always be monitored for suicidal

thoughts and behaviors.47,48

For clinical use. Based on the evidence presented, recommended antidepressant

strategies are that clinicians should:

Use mood stabilizers as first-line treatment, except for patients who have suicidality or severemelancholia

Avoid antidepressants for depressive mixed states or rapid cycling Be more cautious when using antidepressants in bipolar I than in bipolar II disorder Use SRIs before TCAs and MAOIs, and administer at half the dosage used for MDD Taper antidepressant treatment after remission has been achieved for 2 months

Abbreviations

ADHD=attention-deficit/hyperactivity disorder; BRIDGE=Bipolar Disorders:Improving Diagnosis, Guidance, and Education; CBT=cognitive-behavioral therapy;

DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition;

FDA=US Food and Drug Administration; MDD=major depressive disorder;

MAOI=monoamine oxidase inhibitor; NOS=not otherwise specified;

ODD=oppositional defiant disorder; SGA=second-generation antipsychotic,

SRI=serotonin reuptake inhibitor; TCA=tricyclic antidepressant

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2011 ICBD Conference - Practical Applications of New Research in Bipolar Disorder

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