Bipolar Disorder Current Psychiatry

7/29/2019 Bipolar Disorder Current Psychiatry

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supplement to

Challenge in recognition,clinical management, andtreatment of bipolar diorderat the interface of pychiatric

medicine and primary care

This supplement to Current PsyChiatry was developed by

The HWP Group and supported by Pfzer Inc. It has been

edited and peer reviewed by Current PsyChiatry.

Authors

> Henry Chung, MD

> Larry Culpepper, MD, MPH

> Jerey N. De Wester, MD

> Robert L. Grieco, MD> Neil S. Kaye, MD

> Mack Lipkin, MD

> Sherryl J. Rosen, APRN, BC

> Ruth Ross, MA



Challenge in recognition,

clinical management, andtreatment of bipolar diorderat the interface of pychiatricmedicine and primary care

Part 1

Defning the challenge: Recognizingand treating bipolar disorder whereverpatients present . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . s3

Part 2

Challenges in diagnosing bipolar disorder:Identiying mixed episodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . s5

Part 3

Clinical management o bipolar disorder:Achieving best outcomes through acollaborative care model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . s11

Part 4

Treatment by phase: Pharmacologicmanagement o bipolar disorder . . . . . . . . . . . . . . . . . . . s19

Part 5

Recognizing bipolar disorder oninitial presentation: A case study withdecision points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . s28

Dr Chung is Clinical Associate

Proessor in the Department o Psychiatry

at New York University School o Medicine

in New York, NY NY

Dr Culpepper is Proessor and

Chairman in the Department o FamilyMedicine at Boston University School

o Medicine and Chie o the Department o

Family Medicine at Boston University

Medical Center in Boston, MA

Dr De Wester is on the Teaching Faculty

at St. Francis Family Practice Residency

and Hospital Center, and is afliated with

De Wester Family Medicine Treatment

and Research in Indianapolis, IN

Dr Grieco is afliated with Trinity Family

Practice in Beaver Falls, PA, and is coauthor

o The Other Depression: Bipolar Disorder

Dr Kaye is Assistant Clinical Proessor

o Psychiatry and Human Behavior and

Assistant C linical Proessor o Family

Medicine at Jeerson Medical College

in Philadelphia, PA

Dr Lipkin is Proessor o Medicine

and Director, Division o Primary Care,

at New York University School o Medicine,

and Attending Physician at Bellevue Hospital

Center, New York University Medical Center

in New York, NY

Ms Rosen is Vice President and

Psychiatric Clinical Nurse Specialist

at Psychiatric Associates o Lynn, PC,

in Lynn, MA

Ms Ross works with Ross Editorial in

Independence, VA

DISCLOSURE: The above aculty received an

honorarium rom Pzer Inc in connection with

the development o this supplement. Editorial

support was provided by The HWP Group and

was unded by Pzer Inc.

Copyright © 2007 DowDen health MeDia



s Crrnt Psychtry n nvbr 2007 S

Defning the challenge: Recognizingand treating bipolar disorder whereverpatients present

Bipolar disorder oten goes unrecognized by primary care pro-

viders (PCPs) because patients typically present with what

appears to be a major depressive episode and PCPs think it

unlikely that they will see bipolar illness.1-3 In psychiatric settings, too,

bipolar disorder may be undetected or may be recognized only ater

a long delay, possibly because o evolving criteria or diagnosing the

disorder.3, 5-7

There is increasing recognition that bipolar disorder has a spec-

trum o symptom expression rom subthreshold to meeting ull crite-

ria, indicating that bipolar I disorder, at least, may be more common

than the 1% prevalence usually cited in population surveys.1-3,8,9

Further, there is evidence that mixed episodes are not uncommon in

bipolar I and II disorders.4,6,10 In considering the whole spectrum o

bipolar illnesses (bipolar I disorder, bipolar II disorder, cyclothymic

disorder, and bipolar disorder not otherwise specied), some authors

have, controversially, suggested that the prevalence rate may be as

high as 5% in the population.1,3,5

th brd ciiciaPsychiatric clinicians and primary care clinicians may be expected to

meet a patient presenting with bipolar disorder, take a history, di-

agnose the patient’s condition, prescribe drug treatment or it, and

monitor the overall physical health eects o that treatment—all in

brie oce visits.

Frequently, patients are treated or concurrent psychiatric and gen-

eral medical conditions. Medication management o psychiatric treat-

ments may have a direct impact on a patient’s other medical conditions

PaRt 1



S nvbr 2007 n s Crrnt Psychtry

—and vice versa. Mental health care proessionals and

general medical proessionals need to consult and col-

laborate to optimize outcomes or the patient.11-13

priary carAs mentioned, patients with bipolar disorder oten ini-

tially present in a primary care setting with symptoms

o depression. They are less likely to report their manic

and mixed symptoms, such as little need or sleep, in-

fated sel-esteem, or increase in risky or goal-directed

activity.9,10,14,15 Diagnosis o bipolar disorder requires

the compilation o a detailed history o symptoms, be-

haviors, treatment responses, and amily illness, which

presents challenges in the primary care setting.1,16

ma hah carSignicant challenges arise in identiying bipolar pre-

sentations that do not involve the “classic” combination

o pure manic and pure depressive episodes.6,10 Once ac-

curately diagnosed, patients with bipolar disorders re-

quire drug treatments that may have an eect on their

physical health. Patients will benet i mental health

care and primary medical care are viewed collabora-

tively to ensure that psychiatric drug treatment does not

cause or exacerbate other medical conditions, and thatunwanted drug eects are treated medically.17

This journal supplement, along with the compan-

ion supplement to The Journal of Family Practice, is

the end result o a meeting o an expert panel o pri-

mary and psychiatric care clinicians. These clinicians

met to address the issues associated with the diagnosis

and management o patients with bipolar disorder in

various settings. These supplements are a response to

the seminal concerns identied at that meeting and in

subsequent communications.

The chapters that ollow provide practical advice

on recognizing and collaboratively caring or patients

with bipolar disorder, as well as a review o available

pharmacologic treatments or phases and expressions

o the illness. A case presentation examines decision

points about assessment and reerral o a patient who

presents in a primary care setting. We hope that you

nd this inormation helpul in treating your patients

with bipolar disorder. n

Defning the challenge

1. Kay ns. I yr drd ai biar? J Am Board Fam Pract . 2005;18:271-281.

2. Brk m, Ddd s, Brk l. th aag biar dirdr i riary car: a rviw x-iig ad rgig hrai. Psychiatry ClinNeurosci . 2005;59:229-239.

3. Ag J. th rgig idigy hy-aia ad biar II dirdr. J Aect Disord .1998;50:143-151.

4. mar o, si K, lääki s, a.th ciica characriic Dsm-IV biarI ad II dirdr: bai dig r hJrvi Biar sdy (JBs). Bipolar Disord .2004;6:395–405.

5. Brk m, Ddd s, mahi G. ‘Biar ida’: h diagi ad ciica aic biar ixd a. Aust N Z J Psychiatry .2005;39:215-221.

6. mcery sl, Kck pe Jr, p HG Jr, a.Ciica ad rarch iicai h diag-i dyhric r ixd aia r hya-ia. Am J Psychiatry . 1992;149:1633-1644.

7. Bazzi F, Akika H. Irriab-hi dr-

i: rhr vaidai a a biar drivixed ae. J Affect Disord . 2005;84:197-207.

8. mrikaga KR, Akika Hs, Ag J, a.lii ad 12-h rvac biarcr dirdr i h naia Crbid-iy srvy Ricai. Arch Gen Psychiatry .2007;64:543-552.

9. Hirchd RmA, Caabr JR, Wiamm, a. scrig r biar dirdr i hciy. J Clin Psychiatry . 2003;64:53-59.

10. Akika Hs, Brgi ml, Ag J, a. R-vaaig h rvac ad diagiccii wihi h brad ciica c-r biar dirdr. J Aect Disord.

2000;59( 1):s5-s30.11. Bar ms, mcBrid l, Wiird Wo, a. C-abraiv car r biar dirdr: par II. I-ac ciica c, ci, ad c.Psychiatr Serv . 2006;57:937-945.

12. Krah DD, Bar sJ, Caky e, a. pRIsm-e: cari igrad car ad -hacd ciay rrra d i dric. Psychiatr Serv . 2006;57:946-953.

13. uzr J, schba m, Dr BG, a. trarig a hah car a hirac wih gra dici: rr rh rid’ cii. Psychiatr Serv .2006;57:37-47.

14. Hirchfeld RmA, Ca AR, Hol DC, e al.screening for bipolar diorder in paienreaed for depreion in a faily edicineclinic. J Am Board Fam Pract . 2005;18:233-239.

15. Hirchd RmA. Why car ab biardirdr? A riary car ciicia’ gid crig ad rrra. Adv Stud Med .2003;3:223-227.

16. maig Js, Cr pD, sahai A. th bi-

ar cr: a rviw crr ccad iicai r h aag dri i riary car. Arch Fam Med .1998;7:63-71.

17. Fracii lp, Kar s, chair. mig: Advacig h ra wiha i: a ca aci i h aag- abic i. J Clin Psychiatry .2005;66:790-798.

Rrncs




psychiatric clinicians requently encounter patients who pres-

ent with fuctuating and complex mood states, such as de-

pression together with agitation, irritability, and racing

thoughts. These patients may appear restless and driven, but they

do not exhibit the euphoria and grandiosity characteristic o pure

mania. Rather, they may be preoccupied by a dark and distressing

view o the world and o themselves. Their symptoms may swing

rapidly—perhaps over the course o a ew hours—rom depression

to mania and back. In striving to establish the most appropriate di-agnosis and treatment or such patients, the clinician may nd only

limited guidance in the mood disorders section o the Diagnostic

and Statistical Manual of Mental Disorders, Fourth Edition, Text

Revision (DSM-IV-TR™).1

prvac ixd idBipolar mixed episodes may be ar more common than was once

believed. A review o the literature by McElroy et al ound that

rates o mixed symptoms ranged rom 5% to 70% in patients who

have acute mania (due in large part to variations in the criteria

used to dene a mixed episode), with a mean prevalence o 31%.2

It has also been reported that an average o 40% o patients with

bipolar disorder present with a mixed state at some point during

their lietime.3

The prevalence o mixed symptoms is o particular clinical sig-

nicance since mixed bipolar presentations appear to be associated

with poorer short- and long-term outcomes, more protracted epi-

sodes, higher rates o recurrence, and greater risk o suicide than

pure manic episodes.1,2

Challenges in diagnosing bipolardisorder: Identiying mixed episodes

PaRt 2




Dig ixd idThe DSM-IV-TR describes 4 types o mood episodes:

major depressive, manic, hypomanic, and mixed.1 The

diagnostic criteria or a mixed episode are that the con-

ditions or both a manic and a major depressive epi-

sode (MDE), except or duration, must be met nearly

every day or at least 1 week. However, these criteria

do not ully account or cases in which patients display

a mix o symptoms that do not qualiy as a ull mood

episode.2,4,5 Thus, new eorts are being made to denemixed mood states in a clinically relevant way, one that

will encompass the wide range o symptom proles and

patterns that occur.2

Emil Kraepelin originally dened manic-depres-

sive insanity, including a description o multiple mixed

mood states, in 1921.6 Three o the mixed-state sub-

types he described are especially relevant today: (1)

depression with fight o ideas, (2) excited or agitated

depression, and (3) depressive or anxious mania.2,3 Dr.

Kraepelin noted that any combination o mood symp-

toms including both polarities (ie, mania and depres-

sion) would constitute a mixed state.2,4-6

Thus, recent researchers have proposed a model

in which mood disorders are conceptualized as occur-

ring along a continuum (FiguRe 1).2,4,7-10 In this model,

presentations that involve episodes o pure mania or

pure depression would appear at the extreme ends o

the spectrum. Mixed depressive episodes would meet

criteria or MDE but have some manic eatures as well.

Dysphoric mania episodes would meet criteria or man-

ic or hypomanic episodes but present some depressive

symptoms as well.3 This question o how mood disor-

ders are conceptualized has implications beyond mere

psychiatric nosology, since treating patients with bipo-

lar spectrum disorders as i they had purely unipolar

mood disorders can have serious clinical consequences

(as discussed in the section “Clinical implications o

misdiagnosis”).

ty ixd idDysphorc mn

In 1992, McElroy et al proposed operational criteria

or dysphoric (mixed) mania or hypomania, (ie, mania

or hypomania accompanied by prominent depression)

(Table 1).2 According to these criteria, dysphoric or

mixed mania should be diagnosed when a ull manic

or hypomanic episode is accompanied by 3 or more

symptoms o major depression; the presence o 2 de-

pressive symptoms is considered sucient to justiy a

probable diagnosis. At the same time, the researchers

acknowledged the possibility that mixed aective epi-

sodes may represent a heterogeneous condition with

numerous etiologies.2

Mxd dprssv stts

Focusing on the other end o the mood disorder spec-

trum, a number o researchers have described major

depressive episodes characterized by manic or hypo-

manic symptoms (eg, agitation, racing thoughts, ir-

ritability, hostility) that do not meet ull criteria or

mania or hypomania.4,7-11 (The characterization o

Challenges in diagnosing bipolar disorder

Unipolarity Bipolarity

Dsm-IV mixd driv Dsm-IV ixd Dyhric aia† Dsm-IVid* id

majr driv maic rid hyaic id

m criria r a m criria r m criria rmDe b a ha bh a aic id a aic r hyaic aic r ad a mDe (xc id b a hahyaic y r drai) (2 3) driv

y

*Bad dcrii ixd biar a,7 driv ixd a,8 agiad dri,4 irriab-hi dri,9 iar dri wih racig hgh.10

†Bad raia criria rd by mcery sl, a. 1992. 2

Th contnm vw o mood dsordrs

FiguRe 1




Avaiab a www.crrntpsychtry.com

these equivocal episodes as “bipolar” is speculative

and somewhat controversial, since ear o inducing

mania with an antidepressant may lead some clinicians

to withhold antidepressant treatment when it would beappropriate.) Besides these symptoms, mixed depressive

episodes may also have associated eatures characteris-

tic o bipolarity, including high rates o comorbid sub-

stance use and anxiety disorders, suicidality, psychotic

symptoms, postpartum presentations, amily histories

o bipolar disorder, and drug-induced manic symptoms

in response to antidepressant monotherapy.1,3,12,13

evovn crtr

Although researchers continue to debate exactly

what criteria should be used to dene a mixed state,

the psychiatric eld is moving toward a ar more in-

clusive view o the bipolar spectrum o disorders. For

example, in a study published in 2000, participants

were categorized as having a mixed mood episode i

they had either mania or hypomania together with an

MDE—even though the DSM-IV criteria do not con-

sider hypomania with a major depressive episode to be

diagnostic o a mixed state.1,14 The continuing debate

notwithstanding, it is important that psychiatrists rec-

ognize the variety o mixed mood states that can occur,because primary care providers are especially likely to

reer patients with these types o complex presenta-

tions or “treatment-resistant” or “treatment-rerac-

tory” depression due to adverse consequences rom

antidepressant monotherapy. Kaye has suggested that

psychiatrists consider the issue o cycling as opposed

to the issue o polarity when trying to distinguish be-

tween unipolar depression and bipolar disorder/bipo-

lar depression (N. Kaye, written communication, June

2007). Preventing the next cycle, as opposed to simply

treating the current episode, is necessary to appropri-

ately treat this lielong disorder.15

Diria diagi biar raiundrrconton o por prsnttons

Given the potential risks associated with treating bi-

polar disorder with antidepressant monotherapy (as

discussed below), it is essential to determine whether

a patient presenting with depression has a unipolar or

a bipolar mood disorder (Table 2).15-21 Since patientswith bipolar disorder seek treatment or depression 2

to 3 times more oten than or manic symptoms, it is

not surprising that as many as 60% o patients with

bipolar I disorder are misdiagnosed as having unipolar

depression.22,23 Patients with bipolar disorder tend to

have depressive episodes more requently and or lon-

ger periods o time than they experience mania or hy-

pomania.24 And, as indicated, these patients requently

present with mixed mood states. Because a mixed epi-

sode can include elements o depression, and because

the manic aspect o the episode may be characterized

more by restless energy and irritability than by pure

mania, it can be dicult to distinguish a mixed state

rom a simple depressive episode.25 In both cases, pa-

tient history may be the key to a correct diagnosis.

But patients with bipolar disorder are oten unreliable

historians and may not have recognized previous epi-

sodes, especially hypomania, as problematic.15,20,24

Even in psychiatric settings, bipolar disorders o-

ten go undetected or are recognized only ater a long

delay. For example, Mantere et al recently screened

Oprton dnostc crtr or

dysphorc mn or hypomn

Table 1

I. A aic r hyaic ydr by Dsm-III-R criria

II. sia rc a a 3 aciaddriv y r h i bw*

1. Drd d

2. markdy diiihd ir r ar i a,r a a, acivii

3. sbaia wigh gai r icra i ai

4. Hyria

5. pychr rardai

6. Faig r rgy

7. Fig wrh r xciv riarria gi

8. Fig h r h

9. Rcrr hgh dah, rcrr icidaidai, r a cic a r ciig icid

*Three symptoms indicate a defnite diagnosis, 2 symptoms indicate a probable

diagnosis, and 1 symptom indicates a possible diagnosis o dysphoric mania or hypomania.

Adapted rom McElroy SL, et al. Am J Psychiatry . 1992;149:1633-1644; reprinted with

permission.




a median delay o 7.8 years rom

rst episode to diagnosis. In this

study, mixed episodes were de-

tected in 16.7% o patients withbipolar I disorder and depressive

mixed states in 25.7% o those

with bipolar II disorder.8

Cnc mpctons

o msdnoss

Unipolar major depressive dis-

order and bipolar disorder di-

er substantially in their clinical

course and recommended treat-

ment.15 Treating bipolar de-

pression or mixed states with

antidepressant monotherapy may

lead to worsening symptoms, in-

creased mood cycling, unctional

impairment, and even a higher

risk o suicide.15-18 The most re-

cent data show that the use o

antidepressants plus mood stabi-

lizers in bipolar depression con-

veys no additional beneft overmood stabilizers alone.27 Treat-

ment with antidepressants alone

can be particularly risky or pa-

tients with mixed episodes, am-

pliying both the mania and the

depression.25 Mixed episodes

may also be less likely to respond

to antimanic agents.22,24

assssmnt or por dsordr

An assessment or bipolar disorder should be a routine

part o any workup or patients who present with de-

pressive symptoms or report a history o depression.15,24

Because it may be difcult to distinguish unipolar rom

bipolar depression or mixed states on the basis o cur-

rent clinical eatures alone, dierential diagnosis rests on

a disciplined approach to obtaining key history that will

place the patient in or out o the bipolar spectrum. One

approach is to ocus on 5 areas in an orderly manner25:

• Fmy hstory. One rst-degree relative with bipo-

lar disorder or 3 with major psychiatric illness; amily

1630 psychiatric patients with the Mood Disorder

Questionnaire (MDQ) and identied 191 patients

with possible bipolar I and II disorders.8,26 O the 90

patients with bipolar I disorder, a quarter had pre-

viously been undiagnosed. O the 101 patients with

bipolar II disorder—which included patients with bi-

polar disorder not otherwise specied who had hy-

pomania o 2 to 3 days or depressive mixed states,

as well as those who met DSM-IV-TR criteria or

bipolar II—hal had not previously been diagnosed.8

Among the patients in the sample who had previously

been diagnosed with bipolar disorder, there had been


Cnc trs tht sst porty

Table 2

Cors o nss Diriv bhavir i chidhd (ai-dci dirdr,cdc dirdr)

eary ag a ajr driv id (<25 yar)

eary bhavira r ychiaric rb

saa id (r c i wir)

par dri

mi ajr driv id hr drai (<3

h)

Symptomtc pro pychic y

Ayica driv y (g, xciv i,

vraig, wigh gai, ychr rardai)mixd driv id (rc hyaic

y drig driv id)

prid icrad rgy r aciviy wih dcrad

d r ha cad rb v i rcgizd

a i

Fmy hstory Biar dirdr i r-dgr raiv

Aciv dirdr i i grai raiv

Comordty Crr bac ab r hiry bac ab

prb rgaig cr i

Axiy dirdr

Trtmnt rspons Aidra-idcd aia r hyaia

Aidra “war-”

lack r 3 r r adqa aidra ria

Kaye NS. Am Board Fam Prac . 2005;18:271-281.

Ghaemi SN, et al. J Psychiatr Pract. 2005;7:287-297.

Swann AC, et al. Prim Care Companion J Clin Psychiatr. 2005;7(1):15-21.





history o suicide, electroconvulsive thera-

py, mental breakdowns, or drug or alcohol

abuse.

• Spcc sp normts. Decreasedneed or sleep or inability to sleep secondary

to racing thoughts.

• Prson hstory. Early age o symptom

onset, highly recurrent symptoms, ailure to

respond to antidepressants, multiple careers or

marriages, promiscuity, or substance abuse.

• Mood nstty. Mania, hypomania, irri-

tability, sudden mood changes, anxiety, panic,

obsessive-compulsive disorder, eating disorder.

• Dprsson. Atypical, seasonal, postpar-

tum, sudden onset, highly recurrent, melan-

cholic, mixed eatures; suicidality.17,20

Screening tools can help clinicians cor-

rectly identiy bipolar disorder.28 An ideal

tool or use in clinical practice should be brie

and easy or patients to complete without as-

sistance. The MDQ, a brie sel-report orm

consisting o 13 questions plus items assess-

ing the clustering o symptoms and unction-

al impairment, can be completed by patients

in about 5 minutes (FiguRe 2).26 This toolis helpul in screening or current and past

symptoms that suggest bipolarity. It has been

ound to be more sensitive in a psychiatric

(73%) than in a general (58%) population,

and its specifcity has been validated in both

psychiatric (90%) and general medical (93%)

patients.26,28,29 Having a amily member com-

plete the MDQ may be helpul in identiying

symptoms, especially hypomania, that the

patient might not consider a problem.15 O

course, while screening tools may help raise

suspicion or bipolar disorder, they cannot

replace the psychiatrist’s careul assessment

needed to make a clinical diagnosis.

Idiyig crbidychiaric iComorbid anxiety, substance use, and eating

and impulse disorders occur at elevated rates

in patients with bipolar disorder and may

Mood Dsordr Qstonnr

FiguRe

To vw ths Fr, s th

sprt PDF, “md Dirdr

Qiair.”



S10 nvbr 2007 n s Crrnt Psychtry

all be associated with a undamental dysregulation o

mood, behavior, and impulse control.1,30,31 For example,

the National Comorbidity Survey Replication (NCS-R)

ound that among patients who had been diagnosedwith bipolar I disorder, 86.7% had a co-occurring anxi-

ety disorder at some point in their lives; 71.2% had a

co-occurring impulse control disorder; and 60.3% had

a substance-use disorder.30 Comorbid substance use dis-

orders are o particular concern because they can pro-

duce signs and symptoms that mimic depressed, manic,

or mixed states.1 Although most substance-induced

symptoms are short-lived and resolve with sustained

abstinence ater withdrawal, it is not always clear what

role the substance use is playing in the current presenta-

tion o mood symptoms.3,32 Because comorbidity is the

rule rather than the exception in patients with bipolar

disorders—and it is requently the comorbid problem

with which the patient presents—it is important to be

aware o these conditions and to consider their rami-

cations in developing a treatment plan.31

CciPatients with bipolar disorder may have a variety

o mixed presentations, including dysphoric mania,

mixed depression, or a “classic” DSM-IV-TR–dened

mixed episode. Such patients are especially likely to be

reerred or specialized psychiatric care. In these situa-

tions, clear communication among treating clinicians is

the key to successul collaborative care and improved

outcomes or patients. Strategies or such collaborative

care are outlined in Part 3 o this supplement. n


1. Arica pychiaric Aciai. Diagnostic and Statistical Manual o Mental Disorders, 4th ed. Text Revision (Dsm-IV-tR). Wahig-, DC: Arica pychiaric Aciai;2000:345-428.

2. mcery sl, Kck pe Jr, p HG Jr, a.Ciica ad rarch iicai h diag-i dyhric r ixd aia r hya-ia. Am J Psychiatry. 1992;149:1633-1644

3. Akika Hs, Brgi ml, Ag J, a. R-vaaig h rvac ad diagiccii wihi h brad ciica cr biar dirdr. J Aect Disord. 2000;59:5-30.

4. Bazzi F, Kk A, Akika Hs. twarda vaidai a w dii agiad d-ri a a biar ixd a (ixd d-ri). Eur Psychiatry. 2004;19(2):85-90.

5. Akika Hs. Cx biariy: c -ra ad ixd a. Medscape. 2000.

6. Krai e. Manic-Depressive Insanity and Paranoia. 1921. Birigha: Caic md-ici library; 1989.

7. sa t, Bdr R, schrör A, a. Fr-qcy aic y drig a dr-iv id ad iar “driv ixda” a biar cr. Acta Psychiatr

Scand. 2003 Ar;107(4):268-274.8. mar o, si K, lääki s, a.

th ciica characriic Dsm-IV biarI ad II dirdr: bai dig r hJrvi Biar sdy (JBs). Bipolar Disord .2004;6(5):395-405.

9. Bazzi F, Akika H. Irriab-hi dr-i: rhr vaidai a a biar drivixd a. J Aect Disord. 2005a;84(2-3):197-207.

10. Bazzi F. uiar dri wih racighgh: a biar cr dirdr? Psy-chiatry Clin Neurosci. 2005b;59(5):570-575.

11. maj m, pirzzi R, magia l, a. Agiad“iar” ajr dri: rvac, h-gy, ad c. J Clin Psychiatry. 2006;67:712-719.

12. Akika Hs, Bazzi F, prgi G, a. Agiad“iar” dri r-ccaizd a adriv ixd a: iicai r haidra-icid crvry. J Aect Disord. 2005;85:245-258.

13. Caa GB, Rcci p, Frak e, a. th dcr i iar ad biar dirdr: ar-g r a iary arach. Am J Psychia-try. 2004;161:1264-1269.

14. Bar ms, Vja C, Kiia B, a. th Ir-a sa sca: ricai i dicriiaigabiii i a ii, bic cr a.Bipolar Disord .2000;2(4):340-346.

15. Kay ns. I yr drd ai biar? J Am Board Fam Pract. 2005;18:271-281.

16. Ghai sn, Bia ee, Gdwi FK. Di-agig biar dirdr ad h c aidra: a araiic dy. J ClinPsychiatry 2000;61(10):804-808; qiz 809.

17. lib e. Diagig biar dirdr iriary car. Adv Stud Med. 2006;6(6A):s430-s441.

18. sag p, Frak C, Yd mu, a. Biardirdr dci, acrai, ad ra-: riary car hyicia kwdg, ai-d, ad awar. Prim Care Companion

J Clin Psychiatry. 2006;8(3):147-152.

19. Ghai sn, K JY, Gdwi FK. th biarcr ad h aidra viw hwrd. J Psychiatr Pract. 2001;7:287-297.

20. swa AC, Gr B, p Rm, a. pracicac ary rcgii biar dirdr:a riary car arach. Prim Care Compan-

ion J Clin Psychiatry. 2005;7(1):15-21.21. Da AK, o m, Gar mJ, a. scr-

ig r biar dirdr i a riary car rac-ic. JAMA. 2005;293(8):956-963.

22. mcIyr R, Kaza m. th r ayicaaiychic i biar dri ad ax-iy dirdr. Bipolar Disord. 2003;5(2):20-35.

23. Hirchd Rm, lwi l, Vrik lA. prc-i ad iac biar dirdr: hw arhav w ray c? R h aia

driv ad aic-driv aciai2000 rvy idivida wih biar dir-dr. J Clin Psychiatry. 2003;64:161-174.

24. Gdwi FK, Ghai sn. th dic--ra ai wih biar dirdr. I: DwamJ, pi RW, d. The Difcult-to-Treat Psy-

chiatric Patient. Wahig, DC: Aricapychiaric pbihig Ic; 2001:7-39.

25. Gric R, edward l. The Other Depression:

Bipolar Disorder. Bavr Fa, pA: mcKiypr; 2006.

26. Hirchd Rm, Wiia JB, sizr Rl, a.Dv ad vaidai a crigir r biar cr dirdr: hmd Dirdr Qiair. Am J Psychia-

try. 2000;157(11):1873-1875.27. sach Gs, nirbrg AA, Caabr JR,

a. eciv adjciv aidrara r biar dri. N Engl J

Med . 2007;356:1711-1722.28. Badaa CF. A r cr-

ig ad irig biar dirdr. Bipolar

Disord. 2005;7( 1):8-15.29. Hirchd Rm, Ca AR, H DC, a .

scrig r biar dirdr i airad r dri i a aiy diciciic. J Am Board Fam Pract. 2005;18:233-239.

30. mrikaga KR, Akika Hs, Ag J, a.lii ad 12-h rvac biarcr dirdr i h naia Crbid-iy srvy Ricai. Arch Gen Psychiatry.2007;64:543-552.

31. mcery sl, Kwa R, Kck pe Jr. Cr-bidiy aig dirdr wih biar dirdrad ra iicai. Bipolar Disord.2006;8:686-695.

32. Ravi BJ. Dsm-V rarch agda: b-ac ab ychi rbidiy. Schizophr

Bull. 2007;33(4):947-952.

Rrncs



s Crrnt Psychtry n nvbr 2007 S11

A collaborative care model in which psychiatrists communicate

and work closely with primary care providers (PCPs) can lead

to improved overall health and wellness or patients with mental

illness.1 When they join orces with PCPs to treat patients with bipolar

disorder, psychiatrists address many issues related to reerrals, treat-

ment goals, medications, psychosocial interventions, and comorbidities

that are unique to the disease (Table 1).2-18

prig iiv cabraiwih riary car rvidrData rom the National Comorbidity Survey (NCS) and the NCS Rep-

lication indicate that the number o patients seeking care or mental

illness in general medical settings is rising.4 Because it is increasingly

likely that psychiatrists will be asked to evaluate patients who have

already seen a PCP, psychiatrists and PCPs should establish a collab-

orative relationship.5

The ollowing actors aect the overall quality o interactions

between psychiatrists and PCPs:

• Accessibility o physicians to discuss the patient

• Adequacy o the background patient inormation and

history provided

• Communication o expectations

• Communication about ollow-up care.

inormton rom th rrrn prmry cr provdr

To make an accurate diagnosis and prescribe the most appropri-

ate treatment, psychiatrists should obtain a complete patient history

Clinical management o bipolar disorder: Achieving best outcomes through acollaborative care model

PaRt 3




Clinical management o bipolar disorder

Ky prncps n mnn por dsordr n psychtrc cr sttns

Table 1

Dnoss nd • th r ad ira ak i crrcy idi yig biar dirdr (i, diigihig iar rssssmnt biar rai).2 Ahgh hi i raivy raighrward r r aic id, h diagi

ixd id ca b ch r dic giv h rag rai aciad wih ch id. 3

I ay b c cycig a w a ariy.

Rrr • th b r ar baid wh ychiari ad pCp wrk cabraivy.1,4

• I rrrig a ai a pCp r dica car, h ychiari hd rvid irai ychiaric

ad dica hiry, crr dicai, ad ra r rrra. Bca ay pCp ay b

aiiar wih id c dicai d ra biar dirdr, i i h ir h hyicia

ab ay id c h ai ay b xricig h crr dicai rgi.

• Wh a ai i rrrd r a pCp r a a d dirdr, h ychiari hd rq

irai ab h ra r rrra ad h ai’ dica ad dicai hiry.5 prvidig pCp

wh ak rq rrra wih a adard wri rrra r ca h r ha a ri

irai i rcrdd.5 Ar h vaai i cd, h ychiari hd rward a c

rr h dig ad ra rcdai r a h pCp.

Trtmnt os • sa--h-ar ra r ai wih biar dirdr ivv cig h “wh r,”

j h ychiaric dirdr. Ga ra ar y ra ac aic r driv

y b a rdc ra ad d cycig, cr agiai, ad irv ciig1,6

scic ga icd:

• eabihig ad aiaiig a hraic aiac

• mirig h ai’ ychiaric a

• prvidig dcai ab biar dirdr

• prig ra adhrc

• prvig h x cyc/id

• ecragig rgar ar aciviy ad

• Aiciaig rr ad hig ai dv cig ragi

• Idiyig ary warig ig w id

• miiizig cia iair6

Mdcton • pai wih biar dirdr gray d 1 r r dicai ag wih ychhray

achiv h b c.1

• Bca h ajriy ai rad r biar dirdr rciv a a 2, ad 3, dicai,

i i ira ha ach drg irv h rik-b aayi.1,7

• Aidra d a wih a d abiizr ca xacrba d y r ca raid

cycig i ai wih biar dirdr.8-11

• th vari ag d ra biar dirdr hav dir id c ha hd b cidrd

wh akig h ci r a cic ai ad wh irig h ai’ hah a. 1,12

• s ag d ra biar dirdr ca xacrba wigh gai r abic rb r

icra h rik w- wigh gai r iid ad abic abraii. 12

Psychosoc • pychcia irvi—icdig ychhray, dcai, ad r gr—ar kyntrvntons c i h aag biar dirdr ad ca h rdc ra, hr

hiaizai, ad irv ciig ad adhrc dicai.1, 13, 14

Psychtrc • pai wih biar dirdr hav high ra crbid ychiaric dirdr, ciay axiy adcomordty bac dirdr, ha d b ak i acc i ra aig. 11,15,16

• I cig dicai r a ai wih biar dirdr, hd, i ib, ch dicai

iky a b civ r h crbid cdii.16

Mdc • pai wih biar dirdr hav highr ra crai dica cdii, ciay biy adcomordty diab, ha idivida i h gra ai.1,17 th cdii d b rad ad cidrd

i cig ychiaric dicai, ic h ag d ra biar dirdr ca xacrba

h cdii r icra h rik w- wigh gai r iid ad abic abraii.

• Rgar irig h hyica hah ai wih biar dirdr i ia i rig h

b c.18





accompanied by inormation rom the amily and/or

caregivers i possible. The psychiatrist should ask the

PCP about the pattern and duration o symptoms,

exposure to stressul lie events, suicide potential,alcohol and substance use, current and past medical

problems or conditions, and personal and amily his-

tory o psychiatric problems.2,19 In addition, the psy-

chiatrist should obtain a detailed treatment history,

including medications, dosages and duration, symp-

tom responses, and side eects.

The psychiatrist should also ask whether the pa-

tient is to be ollowed in the psychiatric setting or in the

primary care setting. Some o the reasons a patient may

be ollowed in the primary care setting include personal

preerence, lack o resources, and limited insurance cov-

erage.11 In such situations, it is important that the PCP

make it clear that the purpose o the reerral is to obtain

a care plan and arrange or collaboration with the psy-

chiatrist on an ongoing or as-needed basis.

When collaborating, all parties—psychiatric clini-

cian, PCP, and patient—need to agree on who is man-

aging medication adjustments. This is critical so one

clinician does not unintentionally undermine the other’s

treatment plan i the patient calls with a problem.

inormton or th rrrn prmry cr provdr

It is equally important or the evaluating psychiatrist

to provide the PCP with a complete report o the eval-

uation, diagnosis, prescribed treatment, and plans or

uture ollow-up. A time-saving strategy some psychi-

atric oces use to acilitate communication is to send

the reerring PCP a copy o the same comprehensive

initial evaluation note that goes into the patient’s re-

cord. The psychiatrist can also send a copy o ongoing

progress notes whenever there is something that needs

to be communicated to the PCP, perhaps with the most

important points highlighted. The patient signs a re-

lease authorizing collaboration between the psychiat-

ric provider and the PCP at the rst visit (S. Rosen,

written communication, June 2007).

incdn my n th ssssmnt

Because patients with bipolar disorder may have limited

insight into or may deny their own manic or hypomanic

symptoms, it is valuable to include amily members in

the assessment ater obtaining the patient’s consent.2,20

This provides an opportunity to assess the amily’s at-

titudes about such issues as hospitalization and their

ability and willingness to participate in the patient’s

treatment.

assssmnt toos

As noted in Part 2, when making a dierential diag-

nosis or patients with mood disorders, it is important

to identiy current or past manic, mixed, or hypomanic

episodes, as well as any comorbid conditions.21 The use

o a brie and easy-to-complete sel-report tool, such as

the Mood Disorder Questionnaire (MDQ),22 can acili-

tate transer o inormation between PCPs and psychia-

trists. Psychiatrists may want to provide a copy o the

MDQ to PCPs with whom they requently collaborate.

I the PCP has administered the MDQ, it is also helpul

to send the results to the psychiatrist beore the psychia-

trist evaluates the patient.

Aig crbid cdiiComord psychtrc dsordrs

Patients with bipolar disorders have high rates o co-

morbid anxiety, substance use, eating, and personal-

ity disorders.11,15,16 For example, lietime comorbidanxiety disorders were ound in more than 50% and

current anxiety disorders in 31% o the frst 500

patients enrolled in the Systematic Treatment En-

hancement Program or Bipolar Disorder (STEP-BD)

study.23 Further, the lietime risk o anxiety disorders

in bipolar I disorder has been reported to be 93%,

compared with 58% in unipolar depression.24 Bipo-

lar disorder with comorbid anxiety disorders is as-

sociated with more severe symptoms, more requent

episodes, decreased likelihood o recovery, longer

time to remission, poorer role unctioning and qual-

ity o lie, less time euthymic, and a higher incidence

o substance abuse and suicide attempts.16,23-25 Anxi-

ety disorders may be more likely to occur in pa-

tients with mixed episodes.16,24 Bipolar disorder with

comorbid substance abuse is associated with ew-

er and slower remissions, higher rates o suicide

attempts and suicide, and poorer outcomes.19,20,24 Pa-

tients with bipolar disorder and comorbid substance

abuse should be aggressively treated or both disor-

ders.20 Because patients with comorbid psychiatric




disorders may be more difcult to treat, they are es-

pecially likely to be reerred by PCPs or specialized

psychiatric assessment.

Comord mdc condtons

Patients with bipolar disorder have higher rates o con-

ditions that increase their risk o cardiovascular disease

and type 2 diabetes mellitus, including obesity, smok-

ing, hyperglycemia, hypertension, and dyslipidemia.17,26

In one sample, 30% o patients with bipolar disorder

met criteria or the metabolic syndrome, 49% had ab-

dominal obesity, and 48% had hypertriglyceridemia or

were taking a lipid-lowering medication.27 Obesity and

the metabolic syndrome contribute to a worse progno-

sis or bipolar disorder through their negative eect on

general physical well-being and unctioning, quality o lie, and sel-esteem.25,27,28

Certain psychotropic medications, including some

o the newer second-generation antipsychotics (SGAs),

as well as lithium, valproic acid, and carbamazepine,

can contribute to weight gain, and some o the SGAs

also increase the risk o metabolic abnormalities.16,17,27

I weight gain and metabolic problems are a concern,

clinicians may want to select an agent that is less likely

to cause these problems.17 Among available SGAs, olan-

zapine is associated with the greatest increase in weight

and metabolic problems and ziprasidone and aripipra-

zole with the least.12,17

I a patient with bipolar disorder does gain weight

during treatment, the ollowing additional options

should be considered: dietary advice and support; advis-

ing regular aerobic exercise; reerral to specic programs

or weight management; and reerral to a dietitian (es-

pecially i the person has complex comorbid medication

problems).18 It may be particularly useul or the PCP

and the psychiatrist to collaborate in developing such

programs and helping patients ollow through. How-ever, the practitioners must both be clear on who is or-

dering which monitoring tests, on sharing any results

that might signal a health problem, and on how any

changes in psychiatric medications—i needed—will be

undertaken.

Other conditions reported at elevated rates in pa-

tients with bipolar disorder include human immunode-

ciency virus (HIV) and hepatitis C (possibly refecting

increased risk-taking or impulsive behaviors in this pop-

ulation), chronic atigue syndrome, migraine, asthma,

chronic bronchitis, multiple chemical sensitivities, and

gastric ulcer.29,30

Physc hth montorn

A collaborative approach to treating patients with

mental illness can also improve the regularity o their

physical health monitoring. Initial treatment plans

should clearly outline the requency o health moni-

toring as well as a mechanism or regular communi-

cation o results. Although it is not always possible

to ollow all guidelines in every setting, keeping the


Smp chckst or psychtrst’s

rport o psychtrc vton to PCP

FiguRe 1

Rrrig hyicia a ad addr __________________

pai a, addr, h __________________________

prrrd d() cicai

o lr _____________________________________________

o th _________________________________________

Drig h hr _________________________________

ergcy br _________________________________

o Cy dica rcrd ____________________________

o I-r dici _______________________________

o e-ai ____________________________________________

o oi cha ________________________________________

Drig h hr _________________________________

Iiia evaai

o pychiaric diagi r diag ___________________

o R ychgica r rychgicaig ____________________________________________

o

R iagig r abrary di _______________o tra rcribd r rcdd _______________

o Rcdai r cic aci/raby pCp ___________________________________________

o edcaia irai rvidd aiad aiy _________________________________________

o Rrra ad advcacy r r gr _________

o pa r w- _________________________________





ollowing recommendations in mind can help pro-

mote the best use o resources and guide discussions

with patients about disease management and the need

or adherence.Initial physical assessment o a patient with bipo-

lar disorder should include personal and amily histo-

ry; measurement o weight, height, and blood pressure;

calculation o body mass index (BMI); assessment

o tobacco and alcohol use; thyroid, liver, and renal

unction tests; ull blood cell count; blood glucose and

lipid levels; and cardiovascular history.2,18 I clinically

warranted, drug screening, a chest x-ray, an electro-

cardiogram, an electroencephalogram, a computed to-

mography scan, or a magnetic resonance imaging scan

can be ordered.18

When initiating treatment with an antipsychotic, it

is recommended that height, weight, waist circumer-

ence, asting plasma glucose and lipid levels, and blood

pressure be measured.12

During ongoing SGA treatment, patients’ weight

should be reassessed at 4-, 8-, and 12-week intervals ater

initiating or changing treatment and quarterly therea-

ter. For patients who gain 5% or more o baseline body

weight, switching to a dierent antipsychotic should be

considered.12 It is, o course, important to be cautious inmaking changes i a patient is doing well, since a switch

can expose the patient to long periods o drug transition

and a whole new set o potential side eects. At the same

time, patients who gain signicant amounts o weight and

develop lipid and glucose abnormalities can be at risk or

serious health problems and health crises. Thereore, it is

important to conduct a careul review o side eects and

their potential causes when deciding what to do.6 Fast-

ing plasma glucose level and blood pressure should be

assessed 3 months ater initiating an SGA and annually

thereater (more requently i the patient has an elevated

baseline risk or diabetes or hypertension). For patients

with normal lipid levels, testing should be repeated every

5 years or more requently i clinically indicated.12,28 As

mentioned, patients with serious mental illness have an

increased risk or diabetes and heart disease; thereore,

this monitoring is particularly important.31

Prolactin levels should be measured in patients

taking risperidone or other SGAs i they develop low

libido, sexual dysunction, menstrual abnormalities,

gynecomastia, or galactorrhea.18

Thyroid unction should be assessed since patients,

especially those taking lithium, may have normal thy-

roid-stimulating hormone levels but low or low-normal

ree thyroid (T4 or T3) levels. Raising T3 or T4 levels,usually using L-thyroxine, can oten improve response

to lithium or other mood-stabilizing agents.20

An annual examination should be perormed in

patients with bipolar disorder to assess plasma glucose

levels, weight, smoking, alcohol use, and blood pressure,

as well as lipid levels (including cholesterol) in patients

older than 40 years.18

Psychiatrists may nd it helpul to reer their pa-

tients with bipolar disorder to a PCP or the physical

health monitoring described here. I a patient being

treated with an SGA gains substantial weight or devel-

ops metabolic abnormalities and a change o medica-

tions is not possible, a reerral to a PCP or medical

management o these problems can be useul. The psy-

chiatrist and the PCP should coordinate responsibility

or medication prescriptions and ollow-up laboratory

tests (eg, serum drug levels, lipid and glucose levels).15

prici hard aag

ad cabraiDvopn coortv rtonshps

One model o psychiatrist-PCP collaboration would be

or psychiatrists to be part o a multidisciplinary care

team within the primary care setting.32 Each physician

could reer patients to the other as needed or urther

psychiatric or medical assessment; ideally the psychia-

trist would be immediately available when necessary.1

Although such a partnership has the potential to im-

prove patient care, decrease morbidity, reduce health

care costs, and enhance patient satisaction and adher-

ence, it is relatively rare in current treatment settings.32-35

For such a system to work eectively, PCPs need to

increase their knowledge o psychiatric diagnosis and

treatment to better understand when reerral is indi-

cated and to provide ollow-up care or psychiatric

disorders in their own practices. Likewise, given the

increasing ocus on the overall health and wellness o

psychiatric patients, psychiatrists need to gain a bet-

ter understanding o the types o medical problems

that their patients are vulnerable to, both due to the

disorder itsel and as a result o the treatments they




are receiving.18,36 Telemedicine and telepsychiatric con-

sultations also have the potential to improve care or

chronic psychiatric conditions.4,37

A recent, 3-year study at 11 Veterans Aairs hos-pitals compared a collaborative care model or bipolar

disorder with continued usual care. The intervention

consisted o improving patients’ sel-management skills

through psychoeducation, supporting providers’ deci-

sion making through simplied practice guidelines, and

enhancing access to and continuity o care and fow o

inormation through the use o a nurse care coordina-

tor. In this study, the collaborative care intervention sig-

nicantly reduced the number o weeks in an aective

episode, primarily mania. Broad-based improvements

were demonstrated in social role unction, mental qual-

ity o lie, and treatment satisaction.38 These ndings

are similar to those o other studies o collaborative care

o patients with bipolar disorder.36,39

improvn commncton

twn cr provdrs

There is room or improvement in communication be-

tween PCPs and psychiatrists. For example, the Study

o Outpatient Reerral Patterns ound that only 51% o

psychiatrists who saw patients reerred by other physi-cians, mainly PCPs, oten or always received the reason

or the reerral; only 33% oten or always received the

patient’s demographic inormation; only 26% oten

or always received the patient’s medical history beore

the visit; and only 17% oten or always received the

patient’s treatment history. One third o the surveyed

psychiatrists indicated that they oten or always receive

no inormation rom the reerring physician beore the

rst patient visit.5 Although the majority o the respon-

dents reported that the accessibility o PCPs and their

level o satisaction with the overall quality o inter-

actions with PCPs were very good or excellent, 68%

reported that communication with PCPs regarding

ollow-up care was poor to air.5 Psychiatrists identi-

ed medical and treatment histories and the reerring

doctor’s expectations as especially inadequate.5 When

reerring a patient, PCPs need to provide as complete

inormation as possible, including reasons or the re-

erral, urgency o the reerral, medical and psychiatric

history, medication allergies, current therapies and

changes in medications, and results o imaging and

laboratory studies. I this inormation is not provided,

the psychiatrist should request it rom the reerring

PCP. Best outcomes are also achieved when individuals

with bipolar disorder have continuity o care.4,18

Workn s tm: Prmry cr provdrs,

psychtrsts, ptnts, nd ms

It is important that patients perceive their care pro-

viders as a team working together to achieve the best

outcomes. Thus, psychiatrists and PCPs should com-

municate regularly, so that they are both aware o the

patient’s current status and o the recommendations the

other physician has made or ongoing care. It can be

helpul or PCPs to provide copies o the educational

materials on such issues as weight, lipids, and exercise

that they have given patients, and likewise or psychia-

trists to give PCPs copies o educational materials on

bipolar disorder.

A supportive therapeutic alliance between phy-

sicians and the patient with bipolar disorder can in-

crease the patient’s willingness to remain in and adhere

to treatment. Essential components o such an alliance

include expressing concern or the individual’s suer-

ing and communicating appropriate optimism about

the potential or successul treatment while avoidingraising unrealistic expectations. To this end, patients

should be told that they may need to try several di-

erent medication regimens beore they nd one that

works.2,6,20 Patients and their amilies/caregivers

should be encouraged to work collaboratively with

their health care providers and to take an active role

in treatment decisions.6,18 Health care proessionals

should show respect or the patient’s knowledge and

experience o his or her own illness and provide rel-

evant inormation about diagnosis and treatment, in-

cluding proper use instructions and side eect proles

o prescribed medications.6,18 In addition, educating

patients about the reasons or psychiatric consultation

and reassuring them that there will be communica-

tion among the team are important or encouraging

the patient to ollow through with reerrals.4 Families

o patients with bipolar disorder also experience stress

and increased burdens. Among primary caregivers

o 500 patients enrolled in the STEP-BD study, 89%

experienced moderate or high burden related to patient

problem behaviors, 52% experienced role dysunction,






and 61% experienced disruption o household rou-

tine.40 Educating amily members about the biological

nature o the disorder and reerring them to national

and community-based support and advocacy groupscan help them cope with their own burden and help

them to avert uture crises related to the patient’s ill-

ness-related behavior.6,14,15,18,41

Psychosoc ntrvntons

Psychosocial interventions are key components in e-

ectively managing bipolar disorder, especially during

depressive or hypomanic episodes and continuation

and maintenance treatment, as patients are more ca-

pable o taking in and using new inormation at these

times than they are during manic or mixed episodes.6,42

Psychotherapy or bipolar disorder involves a combi-

nation o psychoeducation and other types o therapy,

including cognitive-behavioral therapy, amily-ocused

therapy, interpersonal therapy, and interpersonal and

social rhythm therapy.1,43 Combined with medication,

these strategies can help prolong time to relapse, reduce

symptom severity, and increase adherence.14,41,42,44 E-

ective psychosocial interventions or bipolar disorder

encourage patients to be active collaborators in their

own treatment; emphasize the need or medication toprevent relapse; stress education or patients and ami-

lies about medications, adherence, early warning signs

o relapse, and liestyle changes and stress manage-

ment; and target comorbid psychiatric illnesses.14,25

Although a detailed discussion o specic psycho-

therapeutic techniques or bipolar disorder is beyond

the scope o this chapter, psychiatrists should ensure

that PCPs are inormed about any psychotherapy thatpatients are receiving, including the underlying prin-

ciples, so that the PCP can encourage the patient to

ollow through. Psychiatrists may also be able to as-

sist PCPs in learning more about these techniques so

that they can incorporate them into their own prac-

tices.1 Mood charting (discussed urther in chapter 4)

is especially useul as a monitoring tool that helps

patients see their progress while providing the clini-

cian with important and accurate inormation about

a patient’s disease course.

CciClinicians who treat patients with serious and persis-

tent mental illnesses such as bipolar disorders have

become increasingly aware o the need to ocus on

their patients’ overall well-being. It is not enough to

treat the symptoms o the mental disorder while ig-

noring signs o other health problems that can com-

promise patients’ social and occupational unctioning

and put them at risk or long-term adverse conse-quences. Given this ocus on treating the “whole”

person, a collaborative model in which psychiatrists

and PCPs work together seems likely to promote the

best outcomes or patients. n

1. Kay ns. A riary car arach biardirdr. Adv Stud Med. 2006;6(6A):s442-s458.

2. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. 2d d. nw Yrk:oxrd uivriy pr; 2007.

3. Arica pychiaric Aciai. Diagnostic and Statistical Manual o Mental Disorders, 4thed, Text Revision. Wahig, DC: Aricapychiaric Aciai; 2000. Avaiab a:h//www.ychiaryi.c. AccdFbrary 25, 2007.

4. oa J. pychiaric cai i airiary car ig: hd caichag cabrai? Primary Psychiatry.2006;13(6):41-45.

5. taiia tl, pic HA, Dirich AJ, a. Rr-ra ychiari. Aig h cica-i irac bw ychiary ad riarycar. Psychosomatics. 2000;41(3):245-252.

6. Arica pychiaric Aciai: pracicgidi r h ra ai wihbiar dirdr (rvii). Am J Psychiatry. 2002;159:1-50.

7. lvi J, Chgaa Kn, Brar Js, a. py-

chric drg rcrii ar agai wih biar I dirdr. Bipolar Disord .2000;2(2):120-130.

8. sag p, Frak C, Yd mu, a. Biar di-rdr dci, acrai, ad ra:riary car hyicia kwdg, aid,

ad awar. Prim Care Companion J ClinPsychiatry. 2006;8(3):147-152.

9. Ghai sn, Bia ee, Gdwi FK. Di-agig biar dirdr ad h c aidra: a araiic dy. J ClinPsychiatry. 2000;61(10):804-808; qiz 809.

10. Kay ns. I yr drd ai biar? J Am Board Fam Pract. 2005;18(4):271-281.

11. lib e. Diagig biar dirdr iriary car. Adv Stud Med. 2006;6(6A):s430-s441.

12. Arica Diab Aciai; Aricapychiaric Aciai; Arica Aciai Ciica edcrigi; nrh Arica

Aciai r h sdy obiy. C- dv crc aiychicdrg ad biy ad diab. DiabetesCare. 2004;27(2):596-601.

13. sc J, Girrz mJ. th crr a

ychgica ra i biar dirdr:a yaic rviw ra rvi. Bi-

polar Disord. 2004;6(6):498-503.14. mikwiz DJ. A rviw vidc-bad

ychcia irvi r biar dirdr. J Clin Psychiatry. 2006;67( 11):11-33.

15. Griwd Ks, par lF. maag biardirdr. Am Fam Physician. 2000;62(6):1343-1353, 1357-1358.

16. mcIyr Rs, Karki JZ, Yaha ln. C-rbidiy i biar dirdr: a rawrk rraia ra ci. Hum Psychophar-

macol. 2004;19(6):369-386.17. nwcr JW. mdica rik i ai wih

biar dirdr ad chizhria. J Clin Psy-chiatry. 2006;67( 9):25-30.

18. naia Ii r Hah ad Ciica exc-c (nICe). Bipolar Disorder: The Manage-

ment o Bipolar Disorder in Adults, Children and Adolescents, in Primary and Secondary Care. ld: Briih pychgica sciyad th Rya Cg pychiari; 2006(h://gidac.ic.rg.k/cg38/?c=91523).

Accd oc 10, 2007.19. si sG, Jai KR. th rik icid

Rrncs




i ai wih biar dirdr. J Clin Psy-chiatry. 1999;60( 2):53-56; dici 75-76, 113-116.

20. Gdwi FK, Ghai sn. th dic--raai wih biar dirdr. I: Dwa mJ,pi RW, d. The Difcult-to-Treat Patient.

Wahig, DC: Arica pychiaric pr;2001:7-39.

21. swa AC, Gr B, p Rm, a. pracicac ary rcgii biar dirdr: ariary car arach. Prim Care Companion

J Clin Psychiatry. 2005;7(1):15-21.22. Hirchd Rm, Wiia JB, sizr Rl, a.

Dv ad vaidai a crigir r biar cr dirdr: hmd Dirdr Qiair. Am J Psychia-try. 2000;157(11):1873-1875.

23. si nm, o mW, Wiiwki sR, a. Axiy dirdr crbidiy i biar dirdrai: daa r h r 500 aricia ih syaic tra ehac pr-gra r Biar Dirdr (step-BD). Am J Psychiatry. 2004;161(12):2222-2229.

24. mcInyre R, Kazan m. the role of aypical ani-

pychoic in bipolar depreion and anxiey di-order. Bipolar Disord. 2003;5(uppl 2):20-35.

25. Kck pe. lg-r aag ragi achiv ia ci i ai wih bi-ar dirdr. J Clin Psychiatry.2006;67(- 9):19-24.

26. Wi pW, D’Agi RB, lvy D, a.prdici crary har dia -ig rik acr cagri. Circulation.1998;97(18):1837-1847.

27. Fagiii A, Frak e, sc JA, trki s, a.mabic ydr i biar dirdr: d-ig r h Biar Dirdr Cr r p-yvaia. Bipolar Disord. 2005;7(5):424-430.

28. mcIyr Rs, Karki JZ, Wiki K, a.

obiy i biar dirdr ad ajr dr-iv dirdr: r r a aia c-iy hah rvy a hah adw-big. Can J Psychiatry.2006b;51(5):274-280.

29. Byr J, Kchibhaa m, Grig K, a. mdi-

ca crbidiy i a biar ai cii-ca ai. Neuropsychopharmacology. 2005;30(2):401-404.

30. mcIyr Rs, Karki JZ, sczyka JK, a. mdica crbidiy i biar dir-dr: iicai r cia cad hah rvic iizai. Psychiatr Serv.2006;57(8):1140-1144.

31. C CW, madrchid RW. Cgrcii icrad raiy ra, yar iai , ad ca dah ag bica hah ci i igh a. Prev Chronic Dis. 2006;3:A42. eb 2006 mar 15.

32. Kravic Ve. A arrhi icraig igi-icac. Psychiatric Times. oc 1997:14(10).

33. Ka W, V Kr m, li e, a. Cabra-iv aag achiv ra gid-i. Iac dri i riary car.

JAMA. 1995;273:1026-1031.34. si Ge, Ka WJ, VKr m, a. C-

civ a cabraiv car rgrar riary car ai wih ri d-ri. Am J Psychiatry. 2001;158:1638-1644.

35. Bar ms, mcBrid l, Wiird Wo, a.; C-raiv sdi prgra 430 sdy ta.Cabraiv car r biar dirdr: arII. Iac ciica c, ci, adc. Psychiatr Serv. 2006;57(7):937-945.

36. uzr J, schba m, Dr BG, a.trarig a hah car a h i-rac wih gra dici: rr rh rid’ cii. Psychiatr Serv.

2006;57:37-47.37. Bdhir t. priary car: wi i rviv?

N Engl J Med. 2006;355(9):861-864.38. Bar ms, mcBrid l, Wiird Wo, a. C-

raiv sdi prgra 430 sdy ta.Cabraiv car r biar dirdr: ar

I. Irvi ad iai i a ra-dizd civ ria. Psychiatr Serv.

2006;57(7):927-936.39. si Ge, lda eJ, Bar ms, a. lg-

r civ ad c a yaiccar rgra r biar dirdr. Arch Gen

Psychiatry. 2006;63:500-508.40. prick DA, Rhck RA, mikwiz DJ,

a.; step-BD Faiy exric Cabra-iv sdy Gr. prvac ad crra brd ag cargivr ai wihbiar dirdr rd i h syaictra ehac prgra r BiarDirdr. Bipolar Disord. 2007;9(3):262-273.

41. sajavic m, Davi m, Hrda DR. ehac- ra adhrc ag a-i wih biar dirdr. Psychiatr Serv.

2004;55(3):264-269.42. Kck pe, pri RH, o mW, a. th ex-

r C Gidi sri: ra biar dirdr 2004. Postgrad Med Spec

Rep. Dc 2004:1-116.43. Frak e, swarz HA, Kr DJ. Irr-

a ad cia rhyh hray: aagigh cha biar dirdr. Biol Psychiatry.

2000;48(6):593-604.44. sajavic m, Vai m, Bw FC, a.

tra adhrc wih aiychicdicai i biar dirdr. Bipolar Dis-

ord. 2006;8(3):232-241.





Bipolar disorder is a lielong illness with a broad spectrum o

presentations. The overall goals o bipolar disorder treatment

are to control acute episodes as quickly as possible, prevent or

reduce urther episodes, decrease or eliminate inter-episode symptoms,

and provide support and education to the patient about management

o the disorder.1 Given the complex nature o bipolar disorder, it is

dicult or the patient, who is experiencing depression and mania(sometimes concurrently), to manage and control the illness without

the help o a strong and supportive therapeutic alliance.2

pharacgic hrayThe primary goal o pharmacologic treatment or bipolar disorder is

mood stabilization. Drugs usually considered mood stabilizers include

lithium and the anticonvulsants carbamazepine, valproic acid, and,

more recently, lamotrigine; increasingly, second-generation antipsy-

chotics (SGAs) are being prescribed or this purpose. First-generation

antipsychotics may be eective primarily or mania but are not as well

tolerated as the SGAs, and some studies suggest that they may exacer-

bate depressive symptoms.3

An ideal mood stabilizer would alleviate acute manic, mixed,

and depressive symptoms; not induce the alternate mood symptoms;

and prevent relapses into manic, mixed, or depressive episodes—all

without causing signicant side eects or toxicity. In reality, this is

rarely accomplished by one medication alone. Successul treatment o

bipolar disorder oten requires use o either dierent drugs or di-

erent phases o the illness or a combination regimen. In one study o

a voluntary registry o 457 patients with bipolar disorder, less than

Treatment by phase:Pharmacologic management o bipolar disorder

PaRt 4




Treatment by phase

20% o the group was receiving monotherapy or the

disease. Hal o those who were on a combination regi-

men were taking 3 or more medications, and almost

one quarter o the patients in the survey were taking 4or more drugs or their illness.4

Managing bipolar disorder is something o a balanc-

ing act. It is important to eectively treat acute episodes

and current mood symptoms, and it is also essential to

keep in mind the chronic and cyclical nature o the dis-

ease.2 Table 1 lists medications currently approved by

the US Food and Drug Administration (FDA) or treat-

ment o the dierent phases o bipolar disorder.

Th dprssv phs

The issue o controlling the acute symptoms o a bi-

polar mood episode while also considering long-term

management is particularly pronounced in the depres-

sive phase o the illness, in which patients tend to spend

a majority o time.5 As mentioned previously, patients

in the depressive phase o bipolar disorder are re-

quently misdiagnosed as having unipolar depression,

an error that can have unwanted clinical consequences

because the recommended treatments or the 2 disor-

ders are substantially dierent.6

Antidepressants or unipolar depression may not beeective or the depressive symptoms o bipolar disor-

der. In a recent study by Sachs et al that is part o the

Systemic Treatment Enhancement Program or Bipolar

Disorder (STEP-BD), a large eectiveness trial unded

by the National Institute o Mental Health, adjunctive

antidepressant therapy did not signicantly improve

depressive symptoms o bipolar depression compared

with mood stabilizers alone.7 Furthermore, some stud-

ies have suggested that antidepressants can hasten man-

ic episodes and contribute to rapid cycling in patients

with bipolar disorder, although the ndings o Sachs et

al do not support this when antidepressants are used in

conjunction with mood stabilizers. In addition, 2 Eu-

ropean reviews have reported that patients with bipo-

lar depression responded avorably to antidepressant

therapy.2,8,9 Still, it is considered prudent to prescribe

an antidepressant or a patient with bipolar disorder

only when other treatment strategies have ailed and

the benets are determined to outweigh the risks. It is

worth noting that, according to a small study by Alt-

shuler et al, there may be a subset o patients or whom

ongoing antidepressant use—together with a mood sta-

bilizer regimen—is eective, does not precipitate mania,

and conveys some protection against another depressive

episode.10However, continued antidepressant ecacy in

bipolar depression remains controversial and is consid-

ered by many to be unproven, especially in light o the

longer-term risk o worsening cycling. It is generally rec-

ommended, thereore, that antidepressants be tapered

and discontinued once bipolar depression is controlled.2

Despite these recommendations, antidepressants are

one o the most commonly prescribed classes o drugs

or bipolar disorder in the United States.11

Traditional mood stabilizers have been shown to

have only limited ecacy in the depressive phase o

bipolar disorder. Lithium, or example, is somewhat

Mdctons pprovd y th FDa or

th trtmnt o por dsordr

Table 1

Phase Medications

Dprssv oazai/fxiQiai

Mntnnc Ariirazlarigilihioazai

Mnc AriirazCarbaazi eRChrraziDivarx eR

DivarxlihioazaiQiaiRiridZiraid

Mxd AriirazCarbaazi eRDivarx eRoazaiRiridZiraid

Mnc nd mxd Ariirazpsods wth or Divarx eRwthot psychotc oazaisymptoms Ririd

Ziraid

FDA, US Food and Drug Administration.

Source: Manuacturers’ US prescribing inormation or drugs listed.





eective, but its time to onset during bipolar depres-

sion is 6 to 8 weeks, and the response is less robust

than that seen during mania.1 Lamotrigine has been

shown to be eective in both preventing and treatingdepressive episodes, and it has been recommended as

rst-line therapy or this phase o the disease.12-15

Important new options or treating bipolar depres-

sion are emerging rom among the SGAs. Currently,

quetiapine and an olanzapine/fuoxetine combination

are the only medications with FDA approval or the

treatment o patients with bipolar depression (Table 1).

In placebo-controlled trials, both regimens have shown

signicant ecacy in improving depressive symptoms

in patients in this phase o the disorder. Patients treated

with the olanzapine/fuoxetine combination showed im-

provement compared with those taking placebo, starting

at week 1 and continuing through the 8-week end point.

Patients who received olanzapine alone also showed

greater improvement than did those who received pla-

cebo during all 8 study weeks, but the response or

olanzapine alone was numerically more modest than or

the combination regimen.16 Quetiapine at 300 and 600

mg/d was studied in patients with bipolar I and bipolar

II depression in an 8-week, double-blind, placebo-con-

trolled study. At both doses, quetiapine was superior toplacebo rom baseline through week 8, and these nd-

ings have recently been replicated.17,18

Two recent studies o aripiprazole showed that

when the drug was administered as monotherapy (10

mg/day titrated to 5-30 mg/day)

to patients with bipolar I disorder

who were having a major depres-

sive episode, it was no more eec-

tive than placebo.19 Ziprasidone is

under investigation by its manuac-

turer to determine whether clinical

experience, case reports, and open-

label work that suggest ecacy in

bipolar depression can be repro-

duced in more stringent, blinded,

multicenter trials.

Th mnc phs

The eectiveness o lithium in the

manic phase o bipolar disorder

has been documented over more

than 50 years o testing. The use o valproate and car-

bamazepine is also supported by some 20 years o clin-

ical study.20 More recently, the SGAs have proven to

be eective or treating the manic phase o this disor-der. Aripiprazole, olanzapine, quetiapine, risperidone,

and ziprasidone are FDA-approved or the treatment

o bipolar manic episodes. All 5 medications have

shown ecacy in treating acute manic episodes com-

pared with placebo; however, their times to rst sepa-

ration rom placebo range rom 2 to 7 days. Table 2

presents each medication’s earliest day o signicant

separation rom placebo, measured in controlled

studies.21-31

In cases o severe mania, it is oten recommended

that a combination o an antipsychotic with either

lithium or valproate be used.1 Benzodiazepines, while

not thought to have an antimanic eect, can be a use-

ul addition in the treatment o mania by providing

extra sedation, restoring sleep patterns, and easing

anxiety.1,3

Mxd psods

Acute mood episodes that include signicant symp-

toms o both depression and mania are categorized as

mixed episodes.32 These episodes are dicult to iden-tiy and present a particular challenge to both primary

care providers (PCPs) and psychiatric clinicians. PCPs

sometimes reer patients experiencing mixed episodes

to psychiatrists or “treatment-reractory depression,”

o ec*

Fir sigica

ora mdicai Fir A sarai r pacb

Zprsdon Day 221,22 Day 221,22

arpprzo Day 223 r 424 Day 423,24

Rsprdon Day 325,26, r 727 Day 325 r 726,27

Onzpn Day 728,29 Day 729 r 2128

Qtpn Day 430,31 Day 431 r 730

This table is not derived rom head-to-head studies. It is derived rom the pivotal studies accepted by the US Food and Drug Administration

in support o the indication.*Studies assessed frst signifcant separation rom placebo at dierent days.

Tm to onst o ct o scond-nrton

ntpsychotcs n por mn

Table 2




Treatment by phase

as they do not always recognize these patients as hav-

ing bipolar disorder.

Mixed states are common, troublesome, and un-

derdiagnosed, and present unique treatment concerns.It is estimated that approximately 33% to 40% o pa-

tients with bipolar disorder experience mixed states.33

Clinicians usually are able to identiy depressive symp-

toms ar more readily than manic symptoms in patients

with bipolar disorder, but screening or both hypoma-

nia and mania, especially in the context o a depressed

episode, is an important step in distinguishing mixed

mood rom pure depression.2 Even when properly diag-

nosed and treated, patients who experience mixed epi-

sodes tend to have a slower recovery time and a shorter

time to relapse than do patients with pure manic or

depressive episodes.33 For example, in a 5-year prospec-

tive study, median time to recovery or mixed episodes

or rapid cycling episodes was 17 weeks, compared with

6 weeks or manic episodes and 11 weeks or depres-

sive episodes.34 The cumulative probability o relapse at

6 months ater the frst episode was 36% or patients

with mixed episodes or rapid cycling, 20% or patients

whose last episode was manic, and 33% or patients

with depressive episodes.34

Patients who experience mixed episodes also havehigher rates o both suicidality and substance abuse.

For instance, in a pooled study o more than 500 pa-

tients with bipolar or other major aective disorders

who had a history o at least 1 hospitalization, 29.2%

o patients with mixed episodes had had a recent sui-

cide attempt, compared with 20.3% o patients with

a depressive episode and 2% o manic patients (a sta-

tistically signicant dierence).35 In addition, an inci-

dence o substance abuse was observed in 38.2% o

patients with mostly mixed episodes, compared with

30.3% in the rest o the bipolar population.35

Patients with mixed episodes respond more slow-

ly to and experience less improvement with lithium

than do patients experiencing pure mania.3 Anticon-

vulsants such as valproate may be more eective than

lithium or the treatment o mixed states.1,33 Recent

eorts to identiy other treatment options that will

rapidly relieve both the manic and the depressive

symptoms o mixed episodes have led to the increased

use o SGAs in this context.33 As with mania, rapid

control o mixed states is an important objective.

Trtmnt sss whn psychotc

symptoms r prsnt

Psychotic eatures most requently appear in manic

episodes o bipolar disorder but may occur during anyphase. More than hal o manic episodes have psy-

chotic eatures, and as many as 58% o patients with

bipolar disorder have experienced at least 1 psychotic

episode.1,36 Psychotic symptoms that typically occur

in bipolar disorder are grandiose delusions, such as

an unrealistically infated sense o worth, power, or

knowledge, and depressive delusions, such as personal

inadequacy and disease, paranoid and bizarre delusions,

and hallucinations. Patients who experience psychotic

symptoms during an acute episode may benet rom the

use o an antipsychotic agent.1

Mntnnc thrpy

According to expert consensus guidelines, once an

acute episode has been identied and controlled, the

same medication should be continued at the same dose

that achieved remission.14 Ater a depressive episode,

any antidepressants being used as adjunctive therapy

should be tapered and discontinued when possible.14

Ky ponts n th ovr phrmcoocmnmnt o por dsordr

Several organizations publish treatment and medica-

tion algorithms or bipolar disorder (Table 3).1,14,15, 32,37

Thus, even i the rst medication or dosage prescribed

or a particular patient is not eective, there are many

pharmacologic options and steps in the management

o bipolar disorder.38 Important management compo-

nents to keep in mind are medication adherence, level

o response to the treatment regimen, and possible ad-

verse reactions.

Beore changing therapies or a nonresponsive pa-

tient, the clinician must ensure that medications are

being taken as directed. Nonadherence is high among

patients with bipolar disorder, who have long periods

o normal unctioning and may be in denial about

their illness. Patients with only hypomanic symptom-

atology may not consider their symptoms problematic,

and those with mania may be reluctant to give up the

euphoric eelings and high sel-esteem that can come

with it.1 Thus, ollow-up and patient education about

medication adherence are vital.





amrcn Psychtrc assocton Prctc gdn or

bpor Dsordr1

• Crhiv

• Fr a ac ra

exprt Consnss gdn or bpor Dsordr14

• Dvd by a idd gr ychiari

• Fcd riariy ychharacgy

• srvy xr

Txs impmntton o Mdcton aorthms or

bpor Dsordr15

• Fwchar a ra agrih r dicaiaag

Mt. Sn gdns37

• phyica hah irig ai akigaiychic

Diagnostic and Statistical Manual of Mental Disorders,

Fourth Edition, Text Revision (DSM-iV-TR® )32

• Dcii r r diria diagi ddirdr, icdig biar dirdr

gdns nd orthms or

por dsordr trtmnt

Table 3I the patient is ollowing medication schedules and

directions correctly but improvement is still insucient,

optimizing dosing is the next step in pharmacologic

management. Table 4 gives the recommended dosageso agents or various phases o bipolar disorder.

I response is still less than optimal, treatments

may be switched or augmented. It is important during

this process to keep patients hopeul, or example, by

inorming them that i they have not responded to a

certain class o drugs, they may be more likely to re-

spond to a dierent class.38

Most o the traditional mood stabilizers used or

bipolar disorder can cause signicant side eects; thus,

periodic patient monitoring is crucial during long-term

treatment. Interactions with other psychiatric and non-

psychiatric medications may push a mood stabilizer

into either a subtherapeutic or a toxic range, and the

consequences o overdosage can be serious and even le-

thal.1 Thereore, serum levels o lithium, valproate, and

carbamazepine should be checked regularly and dos-

ages adjusted accordingly to ensure that they are in the

therapeutic range.20 Lithium treatment has been associ-

ated with weight gain and thyroid toxicity,39 and renal

and thyroid unction should be checked every 6 months

to 1 year during treatment.1,39 Side eects o valproatecan include transaminase elevations, hepatic ailure (in

pediatric patients), and, rarely, thrombocytopenia; while

not required, it is recommended that tests o hemato-

logic and hepatic unction be perormed every 6 months

during valproate treatment.1 Treatment with carbam-

azepine calls or complete blood cell counts, platelet

measurements, and liver unction tests every 2 weeks or

the rst 2 months o treatment. Thereater, i laboratory

results are normal, blood cell counts and liver unction

tests should be perormed every 3 months.1 Carbamaze-

pine may decrease levels o valproate, lamotrigine, oral

contraceptives, protease inhibitors, benzodiazepines,

and certain antipsychotics and antidepressants; moni-

toring o serum levels o these drugs is, thus, required

during carbamazepine therapy.1

Ater reviewing data on the metabolic implications

o SGAs, the American Diabetes Association (ADA) and

the American Psychiatric Association (APA) issued a

joint consensus statement concluding that clozapine and

olanzapine have a pronounced risk o metabolic syn-

drome, risperidone and quetiapine exhibit discrepancies

in the data, and aripiprazole and ziprasidone show min-

imal impact on metabolic indices (Table 5).40 The orga-

nizations nevertheless advocate that a patient taking

any SGA be monitored or metabolic syndrome upon

initiation o treatment and then periodically, as shown

in Table 6.40 An individual patient with an elevated

level o risk may require more requent monitoring.40

I a patient’s metabolic condition deteriorates due

to medication (eg, weight gain >5%, increased glyce-

mia, or dyslipidemia), the ADA/APA consensus state-

ment recommends switching to an SGA with a more

avorable metabolic prole, thus reinorcing the

importance o considering the overall health needs

o a patient when choosing a treatment approach.40

However, because antipsychotics are very dierent

medications with distinctive receptor proles, chang-

ing rom one to another can be problematic. Thereore,

it is prudent to ollow a protocol or switching, such

as the gradual approach recommended by the ADA/

APA consensus statement. It calls or cross-titration,

avoidance o abrupt discontinuation o the current




Treatment by phase

Maintenance/

Medication Bipolar Depression Continuation Mania Mixed Episodes

Onzpn/ • tak wih r wih d: nA nA nA

foxtn iiia 6 g/25 g ca;adj ia ciica

r ≤18 g/75 g

(c daiy )

Qtpn • tak wih r wih d: nA • tak wih r wih nA iiia 50 g/d; adj daiy d: iiia 100 g/d;

rach 300 g/d day 4 adj by 100 g/d

(c daiy ) (ax 400 g/d day4) ad h by 200 g/d

(ax 800 g/d day6) ia ciica

r 400 800g/d (dividd d)

Dvprox nA nA • tak wih d: iiia nA 750 g/d (dividd

d); adj iaciica r ≤60

g/kg/d

Dvprox nA nA • tak wih d: iiia • tak wih d: iiia

eR 25 g/kg/d; adj 25 g/kg/d; adj ia ciica r ia ciica r-

≤60 g/kg/d (c daiy) ≤60 g/kg/d(c daiy)

lmotrn nA • tak wih r wih d: nA nA caa wy; arg d

r hray i 200 g/d;adj dwward r ward

drig cadiirai wihhr drg; hraic

aa ccrai abihd; rd prscrn

normton cry

lthm nA • uay 900 1200 g/d bid, • uay 1800 g/d i nA

id r qid; dag b dividd d; dagidividaizd ad r b idividaizd

v ird a 1- r ad r v2-wk irva aiai ird wic wky

ia ciica r i abiizd iabw 0.6 ad 1.2 eq/l; ciica r bwdrig cicad 1.0 ad 1.5 eq/l

rii, ir vry2 h

arpprzo nA • tak c daiy wih r wih • tak wih r wih d: • tak wih r wihd: 15 r 30 g/d i ai iiia 30 g/d ra d: iiia 30 g/d

wh ac y hav ab, 25 g/d ra ra ab, 25 g/db abiizd ariiraz i; ay dcra ra i; ay

15 g/d i w dcra 15 g/d irad (c daiy) w rad

(c daiy)

Continued on page S25

Rcommndd dos nd dmnstrton o FDa-pprovd por mdctons

Table 4





Maintenance/

Medication Bipolar Depression Continuation Mania Mixed Episodes

Onzpn nA • tak c daiy wih r wih • tak wih r wih d: • tak wih r wih

d: 5-20 g/d i ai iiia 10 15 g/d; d: iiia 10 15wh ac y hav adj by 5 g/d g/d; adj by 5 g/d

b abiizd azai ia ciica r ia ciica

≤20 g/d (c daiy) r ≤20 g/d(c daiy)

Crmzpn nA nA • tak wih r wih d: • tak wih r wih

eR iiia 400 g/d; adj d: iiia 400 g/d;

by 200 g/d ia adj by 200 g/d ciica r ≤1600 ia ciica

g/d (dividd d) r ≤1600 g/d(dividd d)

Rsprdon nA nA • tak wih r wih d: • tak wih r wihiiia 2 3 g/d; adj d: iiia 2 3

by 1 g/d ia g/d; adj by 1 g/dciica r ≤6 g/d ia ciica

(c daiy) r ≤6 g/d(c daiy)

Zprsdon nA nA • tak wih d: iiia • tak wih d: iiia80 g/d; arg 120 80 g/d; arg 120

160 g/d by day 2 160 g/d by day 2(dividd d) (dividd d).

note: Abri Abri dbdb wh ak wh ak wih d

wih d

NA, not applicable

Source : US Food and Drug Administration; Manuacturers’ US prescribing inormation or drugs listed.

Rcommndd dos nd dmnstrton o FDa-pprovd por mdctons

Table 4 Continued rom page S24

drug, and dosage determined by the prole o the new

drug.40 Also, there are times when switching may not be

appropriate. For example, i the drug causing the meta-

bolic problem is the only one to which the patient has

responded clinically, eorts should be made to maintain

symptom control and address metabolic concerns.

Byd harachrayPsychotherapy is another important component o

bipolar treatment. Studies o several psychotherapeu-

tic models have shown that amily-ocused, cognitive,

psychoeducational, and interpersonal social rhythm

therapies—which combine interpersonal therapy with

simple techniques to help the patient ollow daily rou-

tines—can all be eective in treating bipolar disor-

der.1,41,42 These interventions allow or dialogue about

ongoing disease management, educate the patient

Wigh Rik r WrigDrg Gai Diab liid pr

Cozpn +++ + +Onzpn +++ + +

Rsprdon ++ D D

Qtpn ++ D D

arpprzo +/- - -

Zprsdon +/- - -

+ = icra c; - = c; D = dicra r

Copyright © 2004 American Diabetes Association. From Diabetes Care ®, Vol. 27, 2004; 596-601.

Reprinted with permission rom the American Diabetes Association

Mtoc cts o

scond-nrton ntpsychotcs

Table 5




Treatment by phase

about medications and the need or adherence, and

provide inormation about the importance o sticking

to a routine and getting enough sleep.11

Psychotherapy can increase medication adherence,

reduce relapse rates, shorten recovery times rom de-

pression, and improve overall patient unctioning.11

Although the best setting or psychotherapy is the o-

ce o a psychiatrist or psychologist (ideally one ex-

perienced in the treatment o bipolar disorder), the

patient can benet greatly i the PCP incorporates the

messages rom psychotherapy at key junctures duringprimary care visits.41

An especially important tool is daily mood charting,

which enables the patient and the physician together to

recognize subtle mood changes and symptoms, identiy

possible triggers and warning signs that might herald an

acute episode, and graphically and eciently monitor

treatment response. Mood charts (available, or exam-

ple, rom http://www.manicdepressive.org/moodchart.

html) can provide the clinician with important and ac-

curate inormation about a patient’s disease course.2, 11

A strong collaborative team that includes both the

psychiatrist and the PCP is also needed to optimally

address the psychiatric and medical comorbidities that

occur in up to 70% o patients with bipolar disorder.6

A particularly prevalent comorbidity in this patient

population is obesity. In one multicenter study, 45% o

patients with bipolar disorder were considered obese

(based on body mass index) compared with 30.5% o

the general population.43 Obesity is a risk actor or

many medical conditions, including diabetes and car-

diovascular disease. In addition, obese patients can have

signicantly shorter times to recurrence o depressive

episodes, more acute episodes over their lietime (both

manic and depressive), and more severe and dicult-to-

treat index episodes.44 It is important to keep in mind

that many medications or bipolar disorder—including

lithium, valproate, and many o the SGAs—are associ-

ated with weight gain.40,45

The prevalence o smoking (another risk actor

or cardiovascular disease) is also high in the bipo-

lar population: an estimated 54% to 68% compared

with 21.5% in the general population.46,47 Obesity

and smoking are considered modiable risk actors

or cardiovascular disease and represent a target or

intervention with exercise, nutrition, and liestyle

counseling.43

CciOptimal management o bipolar disorder involves

maximizing patient unctioning in both the short and

the long term. Together with psychosocial interven-

tions, today’s pharmacologic treatment options or bi-

polar disorder oer greater possibilities or successul

outcomes or these patients than ever beore. n

Assessment Start 4 Weeks 8 Weeks 12 Weeks 3 Month Annually 5 Years

Prson/my hstory X X

Wht (bMi) X X X X X

Wst crcmrnc X X

bood prssr X X X

Fstn cos X X X

Fstn pd pro X X X

BMI, body mass index.

Copyright © 2004 American Diabetes Association, Joint Consensus Statement rom Diabetes Care ®, Vol. 27, 2004; 596-601. Reprinted with permission rom the American Diabetes Association.

Montorn schd or ptnts tkn scond-nrton ntpsychotcs

Table 6





1. Arica pychiaric Aciai. pracicgidi r h ra ai wih bi-ar dirdr. Am J Psychiatry . 2002;159:1-50.

2. Gdwi FK, Ghai sn. th dic--ra ai wih biar dirdr. I: DwamJ, pi RW, d. The Difcult-to-Treat Psy-

chiatric Patient . Wahig, DC: Aricapychiaric pbihig, Ic.; 2001:7-39.

3. Kck pe Jr. maia ad ayica aiychicdrg. Adv Stud Med . 2004;4(10):s895-s898.

4. lvi J, Chgaa Kn, Brar Js, a. py-chric drg rcrii ar agai wih biar I dirdr. Bipolar Dis-ord . 2000;2:120-130.

5. Jdd ll, Akika Hs, schr pJ, a. thg-r ara hiry h wky y-aic a biar I dirdr. Arch Gen

Psychiatry . 2002;59:530-537.6. Hirchd RmA, Vrik lA. Biar dir-

dr—c ad crbidiy. Am J ManagCare. 2005;11(3):s85-s90.

7. sach Gs, nirbrg AA, Caabr JR, a. eciv adjciv aidrara r biar dri. N Engl J

Med . 2007;356:1711-1722.8. Gija HJ, Gdd JR, Rd Jm, a.

Aidra r biar dri: ayaic rviw radizd, crdria. Am J Psychiatry . 2004;161:1537-1547.

9. mr HJ, Grz H, Brich K. D rccacy daa h drg ra acbiar dri r h ii hadrg hr ha aidra ar hra chic? A cca rviw.Eur

Arch Psychiatry Clin Neurosci . 2006;256:1-16.

10. Ahr l, s t, Back D, a. Iac aidra diciai ar acbiar dri rii ra d-riv ra a 1-yar w-. Am J Psychiatry . 2003;160:1252-1262.

11. Kck pe Jr. lg-r aag ra-gi achiv ia ci i aiwih biar dirdr. J Clin Psychiatry .2006;67( 9):19-24.

12. Bwd Cl, Caabr JR, sach G, a. A acb-crd 18-h ria a-rigi ad ihi aiac rai rcy aic r hyaic aiwih biar I dirdr. Arch Gen Psychiatry .2003;60:392-400.

13. Caabr JR, Bwd Cl, sach Gs, a,r h laica 602 sdy Gr. A db-

bid acb-crd dy arigihray i ai wih biar I d-ri. J Clin Psychiatry . 1999;60:79-88.

14. Kck pe Jr, pri RH, o mW, a. tra- Biar Dirdr 2004. th exrC Gidi sri. Postgrad Med Spec Rep. 2004;Dc:1-116.

15. s t, Dhy eB, Hirchd RmA, a,r h txa C Crc pa mdicai tra Biar Dirdr.th txa iai dicai a-grih: da h agrih r ra- biar I dirdr. J Clin Psychiatry. 2005;66:870-886.

16. th m, Via e, Caabr J, a. ecacy azai ad azai-fxi cbi-ai i h ra biar I dri.

Arch Gen Psychiatry . 2003;60:1079-1088.17. Caabr JR, Kck pe Jr, macadd W, a;

Bdr sdy Gr. A radizd, db-bid, acb-crd ria qiai ih ra biar I r II dri. Am

J Psychiatry . 2005;162:1351-1360.

18. Via e, Caabr JR, Gika Jm, a,r h BolDeR sdy Gr. Qiaihray i h ra ai wihbiar I r II dri ad a raid-cycigdia cr: a radizd, db-bid,acb-crd dy. Bipolar Disord .2007:9:413-425.

19. marc Rn, ow R, swaik R, a. twdi vaa h ay ad cacy ariiraz hray i ai wihbiar I dirdr wih a ajr drivid wih ychic ar. prrd a: h 160h Aa mig h

Arica pychiaric Aciai, may 19-24, 2007; sa Dig, CA.

20. Kck pe Jr. th r cd-graiaiychic hray i h raid c-

r ac biar aia. J Clin Psychiatry .2005;66( 3):5-11.21. Kck pe Jr, Vriai m, pki s, a. Zira-

id i maia sdy Gr. Ziraidi h ra ac biar aia: A hr-wk, acb-crd, db-bid, radizd ria. Am J Psychiatry. 2003;160:741-748.

22. pki sG, Kck pe Jr, sga s, a. Zira-id i ac biar aia: a 21-day ra-dizd, db-bid, acb-crdricai ria. J Clin Psychopharmacol .2005;25:301-310.

23. sach G, sachz R, marc R. Ariirazi h ra ac aic r ixdid i ai wih biar I dirdr: a3-wk acb-crd dy. J Psycho-

pharmacol . 2006;20:536-546.24. Kck pe Jr, marc R, trkdiiri s, a; Ar-

iiraz sdy Gr. A acb-crd,db-bid dy h cacy ad ay ariiraz i ai wih ac biaraia. Am J Psychiatry . 2003;160:1651-1658.

25. Hirchd RmA, Kck pe Jr, Krar m, a.Raid aiaic c ririd -hray: a 3-wk icr, db-bid,acb-crd ria. Am J Psychiatry .2004;161:1057-1065.

26. Via e, Khaa B, Gra F, a. Ri-rid i h ra aic r ixdid biar dirdr [Abrac]. pa-r rd a: 41 aa ig h

Arica Cg nrychharac-

gy; Dcbr 8-12, 2002; sa Ja, prRic.

27. erdk m, Karchr K, Gra F, a.Ririd hray i ac biaraia. par rd a h Wrd pychi-aric Aciai mig, J 18-21, 2003;Via, Aria.

28. th m, sagr tm, mcery sl, a; thoazai HGGW sdy Gr. oazaivr acb i h ra ac a-ia. Am J Psychiatry. 1999;156:702-709.

29. th m, Jacb t, Grdy s, a. e-cacy azai i ac biar aia: adb-bid, acb-crd dy. Arch

General Psychiatry . 2000;57;841-849.30. Bwd Cl, Grz H, m J, a. A ra-

dizd, db-bid, acb-crd

cacy ad ay dy qiai rihi a hray r aia i biar

dirdr. J Clin Psychiatry . 2005;66:111-121.31. mcIyr Rs, Brchr m, pa B, a.

Qiai r harid a hrayr biar aia—a 12-wk, db-bid,

radid, ara-gr, acb-c-rd ria. Eur Neuropsychopharmacol .2005;15:573-585.

32. A merican Psychiatric Association. Diagnostic

and Statistical Manual o Mental Disorders,

4th ed, Text Revision. Wahig, DC: Ar-ica pychiaric Aciai; 2000. h// www.ychiary i.c. Accd oc10, 2007.

33. Dr Dl. Ayica aiychic: cacyacr biar dirdr bai.

J Clin Psychiatry . 2005;66( 3):20-27.34. Kr mB. lavri pW, Cry W, a. Bi-

ar I: a v-yar rciv w-. J Nerv

Ment Dis. 1993;181:238-245.35. td l, Badarii RJ, H J, a.

sicid a i ajr aciv dirdr

ai wih crbid bac dir-dr. J Clin Psychiatry. 1999;60( 2):63-69, dici 75-76, 113-116.

36. Kck pe Jr, mcery sl, Hav JR, a.pychi i biar dirdr: h-gy ad iac rbidiy ad cr i. Compr Psychiatry . 2003;44:263-269.

37. mardr sR, eck sm, mir AC, a.phyica hah irig aiwih chizhria. Am J Psychiatry .2004;161:1334-1349.

38. Gdwi FK, Jai KR. Manic-Depressive

Illness: Bipolar Disorders and Recurrent De-

pression. 2d d. nw Yrk: oxrd uivr-iy pr; 2007:702-705.

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Drugs. 2002;16:721-729.40. Arica Diab Aciai, Arica

pychiaric Aciai, Arica Acia-i Ciica edcrigi, nrh Ari-ca Aciai r h sdy obiy.C dv crc a-iychic drg ad biy ad diab.Diabetes Care. 2004;27(2):596-601.

41. Kay ns. A riary car arach biardirdr. Adv Stud Med . 2006;6( 6A):s442-s458.

42. Frak e, swarz HA, Kr DJ. Irr-a ad cia rhyh hray: aagigh cha biar dirdr. Biol Psychiatry 2000; 48:593-604.

43. Fagiii A, Frak e, sc JA, a. mabicydr i biar dirdr: dig rh Biar Dirdr Cr r pyva-ia. Bipolar Disorder. 2005;7:424-430.

44. Fagiii A, Kr DJ, Hck pR, a. ob-iy a a crra c i aiwih biar I dirdr. Am J Psychiatry. 2003;160:112-117.

45. Kck pe Jr, mcery sl. Biar dirdr,biy, ad harachray-aciadwigh gai. J Clin Psychiatry . 2003;64:1426-1435.

46. nwcr JW. mdica rik i ai wihbiar dirdr ad chizhria. J Clin

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Rrncs




the diagnosis and treatment o bipolar disorder poses challenges

to both primary care providers (PCPs), whose patients oten

present with a variety o physical rather than psychological com-

plaints, and psychiatric clinicians, whose patients’ initial presenting

symptoms oten are nonspecic.1-4 The ollowing is a case in point.

iNiTial PReSeNTaTiON

sa D, a 32-yar-d vrwigh arrid wa wih chidr, r-

hr pCp. A h ac, h rark: “I ca y bca I

j ca’ . I igh g 3 r 4 hr a igh. I’ b ik ha r

ab a wk w. I’ acig vryhig, ad I’ aig a vry. I

hik I d a ig i.”

Dcson pont:

• What is the value o a good history in a case such as this one? How

can the patient interview be structured to elicit a good history?

Careul questioning can aid the clinician in drawing a more accu-

rate picture o the patient and tailoring treatment accordingly. At rst

glance, the solution to a sleep disturbance may seem obvious. However,

several red fags have prompted the clinician to probe urther. The clini-

cian responds, “First let’s discuss the problem. How are you handling

the lack o sleep?” Susan D replies:

“I ray d 7 r 8 hr i rdr ci. B i’

y, v hgh I’v b gig y 3 r 4 hr vry

igh, I i hav gh rgy drig h day. I v cad h

garag h hr igh bca y hbad wa’ dig i righ. I’

ik I I ray d , b hi iia r h a wk r

ha b drivig crazy.”

Recognizing bipolar disorder oninitial presentation: A case study withdecision points

PaRt 5




The clinician continues to probe, “What troubles

you the most about this?” Susan D replies:

“mayb i’ r ha j h . A h a

i, I’v b ig icrdiby ad. I cry vr vry-hig ad ayhig. I j k hikig ab hig. A

h ad a wrk, I a a h i hig. I’v b

ig aic wih y hbad. I y a hi vr iy

i. I ca’ ccra a wrk. I a, gai wigh,

giy, ad a r.”

Dcson ponts:

• What are the indications that this could be more

than a problem with sleep?

• What general medical conditions (including sub-

stance abuse) must the clinician rule out? Is the pa-

tient currently taking any medications that could

be contributing to her problems?

• Are there any liestyle or interpersonal issues contrib-

uting to sleep disturbance that should be considered?

• What evidence leads the clinician to suspect a mood

disorder? What are the criteria or a major depressive

episode? What are the criteria or a manic episode?

Insomnia may be due to one or more environmen-

tal or medical conditions.5 In this case, the clinician

needs a more detailed history, because Susan D’s sleepsymptoms have persisted or at least a week, she has

been distractible and irritable, and she has clear mood

disturbances with depressive symptoms.

Susan D states that she has occasional headaches

and she denies substance abuse. Recent laboratory re-

sults, including a thyroid workup, were unremarkable.

With no contributory medical history in this case, medi-

cal causes o insomnia can be ruled out. Susan D takes

no medications, has a history o good sleep hygiene

despite her current sleep issues, and reports no recent

major changes in her liestyle.

Her symptoms point to a mood disorder: depressed

mood, signicant weight gain, insomnia, psychomo-

tor agitation, and diminished ability to concentrate are

all indicative o a major depressive episode.5 Irritated

mood, decreased need or sleep, racing thoughts, and an

increase in goal-directed activity/psychomotor agitation

are symptoms o a manic episode.5

To urther clariy the diagnosis, the clinician asks

about a history o mood episodes, including periods

o depression, irritability, or mania. The clinician asks,

“Have you ever had a period in your lie when you elt

overly sad?” Susan D responds:

“A w yar back, wh I ivd i Aaa, I wa

ad I cd’ g bd ad I wa cryig a h i.my dcr a aidra. I had i

bca i ad ray hyr. my id wa racig

ad I wa’ gig ay I d akig h

dicai ad I br. thr wa a a rid i

cg wh I drd, b i wa’ a bad a h

i i Aaa.”

Dcson ponts:

• What is the signicance o eeling “hyper” or agi-

tated when taking an antidepressant?

• How should the clinician elicit inormation about

previous experience with such symptoms?

Many patients who have bipolar disorder may be

misdiagnosed as having unipolar depression. I an anti-

depressant is prescribed to such patients, they may expe-

rience a switch to mania or a mixed state, as evidenced

by Susan’s agitation—her “hyper” symptoms.6,7

The clinician asks an open-ended question, “Tell

me about other times when you’ve had no sleep and

increased energy...” Susan D replies:

“I cg hr wa a rid wh I did’ , bha wa dir, ic I g a y wrk d. I r-

br ha i ad h rig r.”

Dcson ponts:

• What is the signicance o a prior experience with

sleeplessness?

• What is the signicance o Susan D’s memory o a

positive experience (ie, completion o her work)?

• How does this inormation align with the current

symptoms?

• Is a reerral to a psychiatric clinician necessary, or

can this be managed by a PCP?

Susan’s history o episodes suggestive o mania

ollowing antidepressant treatment and while in col-

lege allows the clinician to rule out major depressive

disorder and to diagnose Susan with bipolar disorder.

It might appear rom the patient’s history that she has

bipolar depression, but the clinical assessment is not

complete. Now the clinician has to determine the phase.

Currently, Susan is experiencing a depressed mood,

sleeplessness, hopelessness, and racing thoughts.




Recognizing bipolar disorder

Sleeplessness may be a symptom o either mania

or depression. An increase in goal-directed activity,

such as seen currently (cleaning out the garage) and

in the past (getting all o her work done during a pe-riod with little sleep), is present in mania but not in

depression.

The clinician concludes that Susan D is most likely

experiencing bipolar disorder, current episode mixed.

Patients having a mixed episode o bipolar disorder

meet the criteria or both a manic episode and a ma-

jor depressive episode nearly every day or at least 1

week.5 (Note that many bipolar disorder cases seen in

primary care may not meet the strict criteria o the

Diagnostic and Statistical Manual of Mental Disor-

ders, Fourth Edition, Text Revision [DSM-IV-TR] or

duration; such cases are classied in the DSM-IV-TR

as “bipolar disorder not otherwise specied.”)5 With

its alternating moods, a mixed episode may well be

one o the most disabling orms o this disorder.

Susan D has had a positive perception o her pre-

vious manic episode. Compliance with medication is

something that she and her clinician should discuss, as

Susan may be among those with bipolar disorder who

believe that some symptoms o mania are needed or

personal success.The PCP is aced with deciding whether to reer

this patient or psychiatric consultation or to retain the

management o her care in the primary care setting.8

He determines through direct questioning that Susan

has not thought about or attempted suicide. Though

agitated, she seems able to discuss and understand her

disorder and her treatment. Through direct questioning

and observation during the oce visit, the clinician de-

termines that Susan is not experiencing hallucinations

and judges that she does not require hospitalization.5

She appears to be a suitable candidate or outpatient

management. This decision will vary depending on a

clinician’s level o comort, experience, and psychiatric

resources available.8

tra rcdaiBased on a diagnosis o bipolar disorder, current

episode mixed, and a phone consultation with a

psychiatric colleague, the PCP determines that the

appropriate way to treat Susan D is to prescribe a

medication or mixed episodes o bipolar disorder.

An important step in treatment selection is to review

the characteristics o the options and select the one

most appropriate or the individual patient.

Dcson ponts:

• What makes an agent a good rst choice or Susan D?

• How do Susan D’s weight and metabolic risk aect

the choice o agent?

• How does Susan D’s previous history o noncom-

pliance aect the choice o agent?

As there are many medications with indications or

mania, a good choice is to start with a medication that

has a specic indication or mixed episodes, namely, ar-

ipiprazole, carbamazepine extended release, divalproex

extended release, olanzapine, risperidone, or ziprasi-

done (See Table).9-21

In addition, Susan D needs a medication that can

be started immediately and will work quickly. Zipra-

sidone has shown separation rom placebo at day 2 in

two pivotal trials, and aripiprazole has shown separa-

tion rom placebo at day 4 in two pivotal trials.9-12

This may be a benet in Susan’s case. However, ra-

pidity o eect cannot be the only actor in the deci-

sion. As an overweight woman, Susan D is already atincreased diabetes, cardiovascular, and cerebrovascu-

lar risk.22 The use o ziprasidone or aripiprazole is

associated with minimal risk o weight gain; in addi-

tion, both drugs have a metabolically neutral prole.22

Because patients with bipolar disorder may be at in-

creased risk or overweight and obesity, therapy with

agents that are associated with lower rates o weight

gain is recommended in the joint consensus statement

issued in 2004 by the American Diabetes Association,

the American Psychiatric Association, the American

Association o Clinical Endocrinologists, and the

North American Association or the Study o Obe-

sity.21,23 This patient already has a history o noncom-

pliance, albeit as a legitimate response to side eects.

It has been noted that o all side eects, treatment-as-

sociated weight gain is the most common reason or

noncompliance.24

Since bipolar disorder is a chronic, lielong illness,

it is important to consider medications that patients

can live with, ones that they can and will take consis-

tently through uture episodes.25





FDa-pprovd mdctons or mxd psods

Table

Onset o Eect*FDA

Approved Day o 1st Neutral

or Signifcant Mean

Mixed Day o 1st Separation Eect on Dosing

Oral Medication Episode Assessment From Placebob Weightc Regimena

Ziraid √ Day 29,10 Day 29,10 Yc tak wih d: iiia 80 g/d;arg 120-160 g/d by day 2(dividd d)

Ariiraz √ Day 212 r 411 Day 411,12 Yc tak wih r wih d: iiia30 g/d ra ab, 25 g/d rai; ay dcra 15 g/d

i w rad (c daiy)Ririd √ Day 314 ,15 r 713 Day 314 r 713,15 nc tak wih r wih d: iiia

2-3 g/d; adj by 1 g/d ia ciica r≤6 g/d (c daiy)

Divarx xdd √ Day 516 Day 516 n16,b tak wih d: iiiara 25 g/kg/d; adj ia

ciica r ≤60 g/kg/d(c daiy)

Carbaazi √ Day 717,18 Day 718 r 1417 Y17,18,b tak wih r wih d: iiiaxdd ra 400 g/d; adj by 200 g/d

ia ciica r

≤1600 g/d (dividd d)oazai √ Day 719,20 Day 720 r 2119 nc tak wih r wih d: iiia

10-15 g/d; adj by 5 g/d ia ciica r≤20 g/d (c daiy)

This table is not derived rom head-to-head studies. It is derived rom () the US prescribing inormation or each drug, ( b) the pivotal studies accepted by the FDA in support o the indication, and ( c) the ADA/APA

2004 Consensus Statement

*Studies assessed frst signifcant separation rom placebo at dierent days.

Fw-The clinician prescribed medication to treat a mixed

episode. Ater weighing the pros and cons o prescrib-

ing a sleep medication as well as the available options, he

also wrote a prescription or a benzodiazepine prn or 2

weeks. The practitioner showed Susan D how to complete

a mood chart. The PCP had a sta member call her 2 days

later to check on how she was doing. Susan D stated:

“I’ ig hyr ad irriab. I had a gd

igh’ a igh, I wa ab ccra a

wrk day. my hbad hik hr’ arady b a

chag i y bhavir.”

Susan D returns to her practitioner 1 week later.

She is calmer and does not complain o any mood

symptoms. Together, she and the clinician review

her mood chart, and the clinician asks directly about

each mood symptom. He conrms that her irritability

continues to decrease and that she is not becoming

depressed. As recommended with all atypical antipsy-

chotics, the clinician rechecks her vitals and labora-

tory results and asks about her benzodiazepine use.

He also asks i she is experiencing any medication

side eects, to determine i a medication adjustment

is needed.



Recognizing bipolar disorder

Dcson ponts:

• Evaluation o treatment outcome

• Is the patient at risk o discontinuing medication

when she eels “well”?The clinician is pleased with Susan D’s response to

medication but counsels her to remain on the medica-

tion even ater she eels she is back to normal. Patients

with bipolar disorder are known to have diculty in

remembering to take a medication when they are not

experiencing symptoms.24 He makes sure she under-

stands the chronic nature o the condition and the

cycling that occurs with bipolar disorder and urgesher to continue to update her mood chart. He asks

her to return in 1 week and makes arrangements to

reer her or counseling to a clinician with expertise

in bipolar disorder. n

1. Craig tKJ, Barda Ap. ABC ahah: c a hah rb iriary car. BmJ. 1997;314:1609-1612.

2. Kr D, lyd K, lwi G, a. Cr c-ia dy y aribi ad rc-

gii dri ad axiy i riarycar. BmJ. 1999;318(7181):436-439.3. mar o, si K, lääki s, a.

th ciica characriic Dsm-IV biarI ad II dirdr: bai dig r hJrvi Biar sdy (JBs). Bipolar Disord.2004;6(5):395-405.

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6. ohr e, Dsza Cm, pick eC, a. I-dicar aia i drd ai: arrciv aayi daa r h Ka-a 1500 dy. J Clin Psychiatry.2007;68:47-51.

7. Fd ad Drg Adiirai: Cr rDrg evaai ad Rarch. Revisions toProduct Labeling. Avaiab a: www.FDA.gv/cdr/drg/aidra/da.h.

Accd Ag 29, 2007.8. maig Js. maag biar dirdr

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ar dirdr i riary car. Adv Stud Med.2006;6( 6A):s406-s416.

Rrncs

Ar i i ra z • Ab i i y

Carbaazi eR • eqr eR

Chrrazi • vari

Divarx • Dak

Divarx eR • Dak eR

larigi • laica

lihi • lihbidoazai • Zyrxa

oazai/xi • sybyax

Qiai • srq

Ririd • Rirda

Ziraid • Gd

Dr brnd Nms

Bipolar Disorder Current Psychiatry

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