bipolar disorder current psychiatry
TRANSCRIPT
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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
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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
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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
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—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
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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
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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
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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.
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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
Challenges in diagnosing bipolar disorder
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.
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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.”
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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
Challenges in diagnosing bipolar disorder
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
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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
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S12 nvbr 2007 n s Crrnt Psychtry
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
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s Crrnt Psychtry n nvbr 2007 S1
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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
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S1 nvbr 2007 n s Crrnt Psychtry
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
Clinical management o bipolar disorder
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- _________________________________
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s Crrnt Psychtry n nvbr 2007 S1
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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
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S1 nvbr 2007 n s Crrnt Psychtry
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,
Clinical management o bipolar disorder
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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
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S1 nvbr 2007 n s Crrnt Psychtry
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.
Clinical management o bipolar disorder
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s Crrnt Psychtry n nvbr 2007 S1
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
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S20 nvbr 2007 n s Crrnt Psychtry
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.
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s Crrnt Psychtry n nvbr 2007 S21
Avaiab a www.crrntpsychtry.com
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
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S22 nvbr 2007 n s Crrnt Psychtry
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.
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s Crrnt Psychtry n nvbr 2007 S2
Avaiab a www.crrntpsychtry.com
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
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S2 nvbr 2007 n s Crrnt Psychtry
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
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s Crrnt Psychtry n nvbr 2007 S2
Avaiab a www.crrntpsychtry.com
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
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S2 nvbr 2007 n s Crrnt Psychtry
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
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s Crrnt Psychtry n nvbr 2007 S2
Avaiab a www.crrntpsychtry.com
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.
39. Badarii RJ. tra rarch i biardirdr: i ad rcdai. CNS
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
Psychiatry. 2006;67( 9):25-30.47. naia Cr r Hah saiic. Health,
United States, 2006. With Chartbook on
Trends in the Health o Americans. Hyavi,
mD: naia Cr r Hah saiic;2006.
Rrncs
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S2 nvbr 2007 n s Crrnt Psychtry
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
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s Crrnt Psychtry n nvbr 2007 S2
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.
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S0 nvbr 2007 n s Crrnt Psychtry
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
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s Crrnt Psychtry n nvbr 2007 S1
Avaiab a www.crrntpsychtry.com
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.
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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
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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