Title: Recognition and Diagnosis of Bipolar Disorder and Its Spectrum
1- Section 1
- Recognition and Diagnosis of Bipolar Disorder and
Its Spectrum
2Spectrum of Bipolar Disorders
- Bipolar I and II
- Hypomania
- Bipolar NOS
- Cyclothymia
- Rapidly changing mood swings
- Major depression with a strong family history of
bipolar disorder - Antidepressant-induced mania and hypomania
- Secondary mania, due to other illness or drugs
Adapted from American Psychiatric Association.
Practice Guideline for the Treatment of Patients
with Bipolar Disorder. 2nd ed. Washington, DC
2002.
3Bipolar Terminology
- A distinct period of abnormally and persistently
elevated, expansive, or irritable mood - Mania
- Lasting at least 1 week with a significant
decline in function - Hypomania
- Lasting at least 4 days, (clearly different from
the usual non-depressed mood), but without a
significant decline in function and no psychosis
American Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision. Washington, DC American
Psychiatric Association 2000.
4Bipolar Terminology (cont)
- Mixed Episode
- The criteria are met both for a manic episode and
for a major depressive episode (bipolar I
disorder) - Cyclothymia
- Alternating mood states that do not meet full
criteria for depressive, manic, or mixed episode
for at least 2 years - Bipolar NOS
- A mood episode that does not meet specific
criteria for any specific bipolar disorder
American Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision. Washington, DC American
Psychiatric Association 2000.
5296.80 Bipolar Disorder NOS
The Bipolar Disorder Not Otherwise Specified
category includes disorders with bipolar features
that do not meet criteria for any specific
bipolar disorder. Examples include
- Very rapid alternation (over days) between manic
symptoms and depressive symptoms that meet
symptom threshold criteria but not minimal
duration criteria for manic, hypomania, or major
depressive episodes - Recurrent hypomanic episodes without intercurrent
depressive symptoms - A manic or mixed episode superimposed on
delusional disorder, residual schizophrenia, or
psychotic disorder not otherwise specified - Hypomanic episodes, along with chronic depressive
symptoms that are too infrequent to qualify for a
diagnosis of cyclothymic disorder - Situations in which the clinician has concluded
that bipolar disorder is present but is unable to
determine whether it is primary, due to a general
medical condition, or substance induced
American Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision. Washington, DC American
Psychiatric Association 2000.
6(No Transcript)
7Diagnostic Criteria for Major Affective Disorders
(DSM-IV)
NOS Not otherwise specified
Adapted from the American Psychiatric
Association Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition, Text Revision.
Washington, DC American Psychiatric Association
2000345-428.
8Diagnosing Bipolar Disorder Challenges
- Variability of age of onset and presentation
- Commonly presenting in the depressed phase and
being misdiagnosed as unipolar depression - Prepubertal onset depression or dysthymia carries
a 2040 risk of bipolar illness - Symptom overlap with other psychiatric conditions
- Previous misdiagnosis common
- Many clinically prominent psychiatric and medical
comorbidities
Thomas P. J Affect Disord. 200479(suppl
1)S3-S8. Berk M, et al. Med J Aust.
2006184459-462.
9The Bipolar Spectrum Stronger
Bipolar I
? 1 week
Bipolar II
? 4 Days
Bipolar NOS
lt 4 Days
Bipolar III
Antidepressant-related hypomania
Adapted from Akiskal HS, Pinto O. Psychiatr Clin
North Am. 199922517-534.
10The Bipolar Spectrum Weaker
Hyperthymic
Bipolar IV
Depressive Mixed State IV ½
Recurrent Unipolar Depression Bipolar V
Adapted from Akiskal HS, Pinto O. Psychiatr Clin
North Am. 199922517-534. Akiskal HS, et al. J
Affect Disord. 200696197-205.
11Bipolar Missed States! (Mixed States)
- Bipolar mixed states depression and mania
co-occurring - Dysphoric mania common especially in women
- Depressive mixed states
- Core of depression, but with racing thoughts
- Mixed hypomania
Berk M, et al. Aust N Z Psych. 200539215-221. Su
ppes T, et al. Arch Gen Psychiatry.
2005621089-1096.
12Self-Rated Screening ToolThe Mood Disorder
Questionnaire (MDQ)
- Hyper or more energetic than usual
- Predominately or thematically irritable
- Distinctly self-confident, positive or
self-assured - Less sleep than usual
- More talkative or speaking faster than usual
- Racing thoughts
- Easily distracted
- Problems at work and socially
- More interest in sex
- Taking unusual risks
- Excessive spending
Hirschfeld RM, et al. J Clin Psychiatry.
20036453-59.
13Bipolar Disorder Diagnosis Is Often Missed
- gt 85,000 US adults surveyed
- Positive screen rate for bipolar illness 3.7
(gt 6 million people in US) - For those with positive screen
Diagnosed withbipolar disorder
20
Neither bipolar disorder nor depression diagnosis
49
Diagnosed with depressionbut not bipolar disorder
31
Only 20 of those with a positive screen had been
told by their doctors that they had bipolar
disorder
Hirschfeld RM, et al. J Clin Psychiatry.
20036453-59.
14Unipolar Misdiagnosis May Lead to Inappropriate
Treatment
Bipolar disorder misdiagnosed as unipolar
depression in 37 of patients (N 85)
100
80
55
60
Patients ()
40
23
20
n 38
n 35
0
RapidCycling
Mania/Hypomania
Development of mania/hypomania or rapid cycling
while taking antidepressants.
Ghaemi SN, et al. J Clin Psychiatry.
200061804-808.
15The Hazards of Misdiagnosis and Delayed
Diagnosis in Bipolar Disorder
- Increased risk of
- Rapid cycling or mixed features
- Suicide attempts or completion
- Violent behavior impulsive behavior
- Sexual and other indiscretions
- Worsening substance abuse
- Loss of job or significant other
- Treatment resistant
16Self-Report Diagnostic Tools For Screening
Bipolar Disorder
17Clinician-Administered Diagnostic Tools For
Screening Bipolar Disorder
18Subthreshold Bipolar Disorder(The Soft Bipolar
Spectrum)
- Boundaries of bipolarity have expanded over the
past decade - Suggest that the diagnostic criteria for
hypomania need revision - Further study is needed to evaluate the hard
and soft definitions of bipolar II, minor
bipolar disorder, and hypomania - A more expansive definition of bipolar II yields
a cumulative prevalence rate of 10.9, compared
to 11.4 for broadly defined major depression
Akiskal HS. Curr Psychiatry Rep.
200241-3. Angst J, et al. J Affect Disord.
200373133-146.
19The Rule of 3 Hinting at Soft Bipolarity (NOS) in
a Clinically Depressed Person
- Three or more
- Major depressive episodes
- Failed marriages
- Failed antidepressants trials
- Distinct professions
- First degree relatives (or generations) with
affective illness - Fields of eminence in the family
- Substances of abuse
- Impulsive behaviors (gambling, car racing,
sexual, etc.) - Individuals dated simultaneously
- Simultaneous jobs
- Languages (for US-born citizens)
- Triad of past histrionic, psychopathic, or
borderline diagnoses - Triad of red car, necktie, or belt
Akiskal HS. J Affect Disord. 200584279-290.
20Importance of Interviewing the Patient and Their
Family
- Patients admitted with major depression
- NIMH study
- Step 1 Patient screened for bipolar disorder
- Step 2 Family member interviewed (by another
investigator interested in genetics) - Result Twice as many bipolar I diagnoses from
interviewing both the patient and a family member
Blehar MC, et al. Psychopharmacol Bull.
199834239-243.
21Physicians Must Use Patient Perspectives to
Improve Diagnosis and Care
- Factors Necessary for Recovery
- Communication between patient and physician best
chance for recovery when patient feels hes being
heard physician must try to understand how the
world looks through patients eyes - Treatment plans that include patient input and
preferences physician must discuss all options
so patient has complete understanding of illness - Recovery-oriented treatment based on mutually
agreed goals so patient feels like a partner in
care
Lewis L, et al. Adm Policy Ment Health.
200532497-503.
22Take Home Messages
- Bipolar disorder can masquerade in different or
mixed mood states - Bipolar disorder is often misdiagnosed as
depression due to the prevalence of depressive
episodes often as the presenting phase - Misdiagnosis can have serious detrimental effects
on treatment effectiveness and outcomes
23 24ComorbiditiesThe Rule Not the ExceptionThe
Multidimensionality of Bipolar Disorder
DiabetesMellitus
Cardio-vascular
PainDisorders
Obesity
Migraine
Comorbidities Medical Psychiatric
BipolarDisorder
Substance Abuse
PersonalityDisorders
EatingDisorders
ADHD
AnxietyDisorders
ImpulseControl
McIntyre RS, et al. Human Psychopharmacol.
200419369-386.
25Psychiatric Comorbid Conditions in Bipolar
Disorder Patients
Allergies, asthma, migraine, and chronic fatigue
1. Hilty DM, et al. Psychiatr Serv.
199950201-213. 2. Krishnan KRR. Psychosomatic
Med. 2005671-8. 3. Brown ES. Psychiatr Clin N
Am. 200528421-425. 4. Singh JB, et al. Bipolar
Disord. 20068696-709.
26Psychiatric Comorbidities Occur Frequently and
Can Complicate Diagnosis of Bipolar Disorder
- Additional axis I disorder
- 65 of bipolar patients have 1 or more
- Nearly 25 have 3 or more
- Lifetime prevalence
- 61 substance abuse
- 42 anxiety disorders
- Comorbid conditions can mimic mood symptoms, mask
them, or exacerbate them
McElroy SL, et al. Am J Psychiatry.
2001158420-426.
27High Number of Lifetime Comorbid Axis I
Disorders in Both Bipolar I and II Patients
Percent
McElroy SL, et al. Am J Psychiatry.
2001158420-426.
28Bipolar Disorder and Prevalence of Anxiety
Disorder
- An anxiety disorder is the most prevalent
- Social phobia generalized anxiety disorder
panic disorder obsessive-compulsive disorder
posttraumatic stress disorder - Co-occurrence of anxiety disorder associated
with - Earlier age of onset of mood symptoms
- Greater number of depressive symptoms
- Suicidality
- Greater comorbidity of substance abuse and eating
disorders
- Keck PE, et al. J Clin Psychiatry. 200667(suppl
1)8-15. - Simon NM, et al. Am J Psychiatry.20041612222-222
9.
29Bipolar Disorder and Frequency ofAnxiety Disorder
McIntyre RS, et al. Bipolar Disord.
20068665-676.
30Bipolar Disorder and Posttraumatic Stress
Disorder
- Prevalence rates vary from 5401,2,3,4,5
- More likely in women, separate course from
bipolar disorder 4 - Arises in about 1/3 of adults with bipolar
disorder who survived severe childhood abuse3 - In 137 patients with bipolar disorder following
September 11 terrorist attacks, PTSD was
associated with hypomanic, manic, or mixed mood
state at the time of trauma6 - Manic symptoms may predispose to adverse sequelae
following traumatic event
1. Kessler R, et al. Arch Gen Psychiatry.
1995521048-1060. 2. McElroy SL, et al. Am J
Psychiatry. 2001158420-426. 3. Goldberg JF, et
al. J Psychiatr Res. 200539595-601. 4.
Strakowski SM, et al. J Clin Psychiatry.
199859465-471. 5. McIntyre RS, et al. Bipolar
Disord. 20068665-676. 6. Pollack MH, et al. J
Clin Psychiatry. 200667394-399.
31Treatment of Bipolar Disorders and Psychiatric
Comorbidities
Antidepressants may trigger mania or destabilize
bipolar disorder
Keck PE, et al. J Clin Psychiatry. 200667(Suppl
1)8-15.
32Bipolar Disorder and ADHD
- Common features
- Impulsivity
- Attention problems
- Conduct problems
- Substance use
- Poor school or work performance
- Relationship problems
Distinguishing features
Comorbidity more common in childhood than adult
onset bipolar disorder.
Slide courtesy of Roger McIntyre, MD and Robert
M. Post, MD.
33Lifetime Prevalence of Substance Use Highest in
Bipolar Disorder
9
70
8
61
60
7
48
47
50
6
36
5
40
33
Percent
31
Odds Ratio
27
4
30
3
20
2
10
1
0
0
Major Depression
OCD
Panic
Bipolar I
Bipolar II
Dysthymia
Schizophrenia
Regier DA, et al. JAMA. 19902642511-2518.
34Course of Substance Use Disorder During Bipolar
Disorder
- Drug use primarily cannabis
- Alcohol use always associated with affective
symptoms - Cannabis use somewhat common in the absence of
affective symptoms - Locked cycling relatively unusual
Strakowski SM, et al. J Clin Psychiatry.
199859465-471.
35Substance Use Disorder Onset With Bipolar
Disorder Onset
- SUD precedes BPD in
- 69 (Strakowski et al 1996, 1998)
- 53 (Winokur et al 1995)
- 91 (Kovasznay et al 1993)
- 59 (Feinman Dunner 1996)
- SUD is commonly antecedent
- Does relative age at onset affect course?
36Impact of Substance Abuse on Bipolar Course of
Illness
- More
- Early onset - unmasking
- Suicidality
- Mixed or dysphoric mania
- Rapid cycling
- ER visits and hospitalizations
- Neuronal loss?
- Less
- Compliance
- Symptom remission
- Treatment (lithium) response
Goodwin Jamison. Manic Depressive
Illness.1990. Goldberg JF, et al. J Clin
Psychiatry. 199960733-740. Frye MA, et al. Mod
Probl Pharm. 19972588-113. Strakowski SM, et
al. Int J Psychiatry Med. 199424305-328.
37Treatment of Co-occurring Bipolar Disorder and
Substance Use Disorders
- Few controlled treatment studies in bipolar
disorder - Must make inferences from data in primary
substance disorders - Combination of psychotherapeutic interventions
and pharmacotherapies targeting both disorders
optimally - Earlier recognition and treatment of bipolar
disorder may prevent substance disorder
Levin FR, et al. Biol Psychiatry. 200456738-748.
38Substance Use Disorder in Bipolar Disorder
Treatment
Bipolar
Substance Drug
Disorder Abuse Lithium /- VPA CBZ
/- TPM -/ Antipsychotics -/? Antidepressa
nts /- /- Naltrexone -/? Disulfiram - AA/Be
havioral /-
Slide courtesy of Stephen M. Strakowski, MD.
39Bipolar Disorder and Substance Abuse Treatment
Response
- Tohen et al (1990)
- 24 lithium-treated BP patients - alcoholism
predicted shorter remission - Weiss et al (1998)
- Self-report compliance 21 compliance lithium vs
50 divalproex in 44 bipolar-SUD patients - Goldberg et al (1999)
- 204 substance abusers who received valproate or
carbamazepine had remission of their bipolar
disorder more often than substance abusers who
received lithium alone (P lt 0.05) - Salloum IM (2005)
- VPA found to be effective with co-occurring
alcohol dependence - Weiss et al (2005)
- Patients with bipolar disorder who experience
sustained recovery from SUDs have a better QOL
than with an active SUD - Patients with no SUD history had the best QOL
Tohen M, et al. J Affect Disord.
19901979-86. Weiss RD, et al. J Clin
Psychiatry. 199859172-174. Goldberg JF, et al.
J Clin Psychiatry. 199960733-740. Salloum IM,
et al. Arch Gen Psychiatry. 20056237-45. Weiss
RD, et al. J Clin Psychiatry. 200566730-735.
40Accelerated Cycling Bipolar Disorder and
Borderline Function or Personality Disorder
Distinguishing Features
Slide courtesy of Roger McIntyre, MD.
41Bipolar Disorder and Borderline Personality
Disorder
- Only modest association
- Patients with borderline personality disorder vs
other personality disorders had higher
co-occurrence (19.4) of bipolar disorder - Those with other personality disorders and
bipolar disorder had more new onset borderline
personality disorder (25) than those without
bipolar disorder (10)
Gunderson JG, et al. Am J Psychiatry.
20061631173-1178.
42Medical Comorbidity in Bipolar Disorder A
Population-Based Survey
Significantly higher than no bipolar (P lt 0.05)
Adapted from McIntyre RS, et al. Psychiatr Serv.
2006571140-1144.
43Medical Comorbidities With Bipolar Disorder
- Cardiovascular disease
- Increased mortality in male inpatients with
bipolar disorder 1.87 - Obesity
- Central obesity more common, especially with
antipsychotics - Diabetes
- Increased prevalence 9.9 expected prevalence
3.4 - Neurological disorders
- Migraine prevalence 25 of men, 27 of women
rate in men is almost 5x general population - Chronic pain syndromes
Elmslie JL, et al. J Clin Psychiatry.
200061179-184 Cassidy F, et al. Am J
Psychiatry. 19991561417-1420 Weeke A, et al. J
Affect Disord. 198713287-292 Mahmood T, et al.
J Affect Disord. 199952239-241 Schiffer RB, et
al. Am J Psychiatry. 198614394-95.
44Correlates of Obesity in Patients With Bipolar
Disorder
- Hypertension
- Diabetes mellitus
- Arthritis
- Male
- Exposure to 1 weight-increasing psychotropic
- Comorbid binge-eating disorder
- gt 4 manic episodes
- 1 suicide attempt
- Limited occupational functioning
Stanley Foundation Bipolar Treatment Outcome
Network (N 644) McElroy SL, et al. J Clin
Psychiatry. 200263207-213.
45Bipolar Disorder and Type II Diabetes
1. Cassidy F, et al. Am J Psychiatry.
19991561417-1420. 2. Regenold WT, et al. J
Affect Disord. 20027019-26. 3. Ruzickova M, et
al. Can J Psychiatry. 200348458-461. 4.
Kilbourne AM, et al. Bipolar Disord.
20046368-373.
46Comorbid Restless Leg Syndrome (RLS) and
Iatrogenic Mania
- Dopamine agonists (such as pramipexole,
ropinirole, used to treat RLS and Parkinsons
disease) may induce iatrogenic mania such as - Gambling
- Hypersexuality
- Impulsive shopping
Singh A, et al. Am J Psychiatry.
2005162814-815. Weintraub D, et al. Arch
Neurol. 200663969-973.
47Unique Treatment Challenges of Parkinsons
Disease
- Depression and anxiety are common
- Motor on-off phenomenon common and associated
with mood fluctuations - Patients with major affective disorder have about
2-fold increased likelihood of developing
Parkinsons disease - Dopamine agonists may worsen mania in persons
with co-occurring bipolar disorder - Some dopamine agonists, such as pramipexole, also
have demonstrated antidepressant efficacy as
adjuncts to mood stabilizers, with low risk of
inducing mania, in preliminary placebo-controlled
trials - Physicians treating Parkinsons patients should
be alert for symptoms of bipolar disorder
Ferreri F, et al. Can Med A J. 20061751545-1552.
Nilsson FM, et al. Acta Psychiatr Scand.
2001104380-386. Goldberg JF, et al. Am J
Psychiatry. 2004161564-566. Zarate CE Jr, et
al. Biol Psychiatry. 20045654-60.
48Medical Comorbidities With Bipolar Disorder
- Some medications increase risk for weight gain,
diabetes, metabolic syndrome, and cardiovascular
disease - Measure waist circumference, BMI, weight, blood
pressure, glucose - Encourage diet and exercise
- Monitoring for drug toxicity is essential
- Routine monitoring of mood stabilizers
recommended every 6 months - Thyroid function tests for lithium
- CBC and hepatic function for valproate and
carbamazepine - Triglycerides for atypical antipsychotics
Kilbourne AM, et al. J Affect Disord. Epub ahead
of print. Suppes T, et al. J Clin Psychiatry.
200566870-886.
49General Principles in Treatment of Comorbidity
in Bipolar Disorder
- Address bipolar disorder and its comorbidities
concurrently - Use medications that treat both disorders
- Use medication with least abuse potential and
least toxicity - Use doses that are below the side effects
threshold - Most treatment of psychiatric comorbidities is
off-label - Maximize the use of nonpharmacologic treatment
- Patients with comorbidities are at greater risk
for medication nonadherence
50Section 3 Treatment of Bipolar Disorder
51Therapies With Bipolar Disorder Indications
Limited data Physicians Desk Reference. 61st
ed. Montvale, NJ Medical Economics Co 2007.
52TIMA Algorithm for Treatment of Acute Manic
Episodes (Stages 12)
Stage 1 Monotherapy 1ALithium, valproate,
atypicals excluding olanzapine and clozapine
1B Olanzapineor carbamazepine
ResponseContinue with therapy
NonresponseTry alternate monotherapy
Stage 2 Two-drug combination Lithium,
valproate, atypical antipsychoticChoose 2 (not 2
atypicals, not aripiprazole or clozapine)
ResponseContinue with therapy
Use targeted adjunctive treatment as necessary
before moving to next stage. Agitation/Aggression-
clonidine, sedatives Insomnia-hypnotics
Anxiety-benzodiazepines, gabapentin. All agents
in Stage 1A and 1B are indicated for acute mania
associated with bipolar I disorder. Safety and
other concerns led to placement of olanzapine and
carbamazepine as alternate first-stage choices.
Suppes T, et al. J Clin Psychiatry.
200566870-886.
53TIMA Algorithm for Treatment of Acute Manic
Episodes (Stages 34)
Suppes T, et al. J Clin Psychiatry.
200566870-886.
54Mixtures of Manic and Depressed Symptoms Are
Commonly Seen
Depressive Mixed States1
Mixed Mania
Dysphoric Mania
Full Mania
Full Mania
2 Mania Symptoms
Mania MDE
2 Depressive Symptoms
Full MDE
Full MDE
MDE major depressive episode 1. Benazzi F.
Psychiatry Res. 2004127247-257. 2. Maj M, et
al. Am J Psychiatry. 20031602134-2140. 3.
Akiskal HS, et al. J Affect Disord.
200585245-258.
Agitated depressions? 2,3
55Conventional vs Atypical AntipsychoticsSide-Effe
ct Profiles
Key 0 absent ? minimal mild
moderate severe TRZ Thioridazine HAL
haloperidol CLZ clozapine OLZ olanzapine
RIS risperidone QTP quetiapine ZIP
ziprasidone ARI Aripiprazole a Minimal weight
gain in long-term treatment.
Tandon R, Jibson MD. Psychoneuroendocrinology.
200328(suppl 1)9-26. Physicians Desk
Reference. 61st ed. Montvale, NJ Medical
Economics Co 2007.
56FDA Black Box Warnings
- Clozapine
- Agranulocytosis, seizures, hypotension,
myocarditis - Valproate
- Fetal neural tube defects, hepatic failure,
hemorrhagic pancreatitis - Lamotrigine
- Serious rashes
- Lithium
- Toxicity close to therapeutic levels
- Carbamazepine
- Agranulocytosis
- Aplastic anemia
- Second generation antipsychotics
- Increased mortality in elderly patients with
dementia-related psychosis
Prescribing Information. In Physicians Desk
Reference. 61st ed. Montvale, NJ Medical
Economics Co 2007
57Treating Bipolar Depression
- Monotherapy or combination therapy
- Lithium
- Novel antipsychotics
- Anticonvulsants
- Other strategies
- Add-on antidepressant (not as monotherapy)
- Electroconvulsive therapy (ECT)
While monotherapy is the goal of most
practitioners, the inherent nature of bipolar
disorder makes combination therapy the rule
rather than the exception.
Young LT. J Psychiatry Neurosci.
20042987-88. American Psychiatric Association.
Am J Psychiatry. 20021591-50.
58TIMA Bipolar Treatment of Acute Depressive
Episodes (Stages 13)
Taking no antimanic, with history of severe
and/or recent mania
Taking no antimanic, without history of severe
and/or recent mania
Taking otherantimanic
Taking Li
Increase to 0.8 mEq/L
(continue)
Stage 1
Antimanic LTG
LTG
Stage 2
OFCa or QTPa
Stage 3
Combination from Li, LTG, QTP, or OFC
aNote safety issue described in reference listed
below (ie, olanzapine is associated with weight
gain, quetiapine is associated with sedation and
somnolence). Li lithium LTG lamotrigine OFC
olanzapine-fluoxetine combination QTP
quetiapine.
Suppes T, et al. J Clin Psychiatry.
200566870-886.
59TIMA Bipolar Treatment of Acute Depressive
Episodes (Stages 45)
Stage 4
Li, LTGb, OFC, VPA, or CBZ SSRIc, BUP, or VEN
or ECT or QTP
Stage 5
MAOIs, tricyclics, pramipexole, other AAPsa,
OXC, other combinations of drugs at stages,
inositol, stimulants, thyroid
aNote safety issue described in reference listed
below (ie, olanzapine is associated with weight
gain, quetiapine is associated with sedation and
somnolence). bLamotrigine has limited antimanic
efficacy and, in combination with an
antidepressant, may require the addition of an
antimanic. cSSRIs include citalopram,
escitalopram, fluoxetine, paroxetine, sertraline,
and fluvoxamine. Evidence supported by
randomized controlled clinical trials with large
effect sizes. AAP atypical antipsychotic BUP
bupropion CBZ carbamazepine CONT
continuation ECT electroconvulsive therapy
Li lithium LTG lamotrigine MAOI
monoamine oxidase inhibitor OFC
olanzapine-fluoxetine combination OXC
oxcarbazepine QTP quetiapine SSRI selective
serotonin reuptake inhibitor VEN venlafaxine
VPA valproate.
Suppes T, et al. J Clin Psychiatry.
200566870-886.
60Quetiapine Monotherapy for the Treatment of
Bipolar Depression
MADRS Total Score
Study Week
Study Week
1
2
4
3
6
5
7
8
0
1
2
4
3
6
5
7
8
0
0
0
Placebo (n 169)
Placebo (n 161)
Mean Change From Baselinea
QTP 300 mg/d (n 172)
QTP 300 mg/d (n 155)
QTP 600 mg/d (n 151)
QTP 600 mg/d (n 170)
-4
-4
-8
-8
-12
-12
Improvement
-16
-16
BOLDER I N 511
BOLDER II N 467
-20
-20
P lt 0.01 vs placebo, P lt 0.001 vs placebo
aValues are least squares mean
Calabrese J, et al. Am J Psychiatry.
20051621351-1360.
Thase ME, et al. J Clin Psychopharmacol.
200626600-609.
61BOLDER II MADRS Items
Quetiapine 300 mg (n 155)
Apparent sadness
Quetiapine 600 mg (n 151)
Reported sadness
Placebo (n 161)
Inner tension
Reduced sleep
Reduced appetite
Concentration difficulties
Lassitude
Inability to feel
Pessimisticthoughts
Suicidal thoughts
0
10
20
30
40
50
60
70
80
Improvement from Baseline in Mean Score
N 467 P lt 0.05 P lt 0.01 P lt 0.001 vs
placebo (P-values ANCOVA, change from
baseline) Week 8 assessment
Thase ME, et al. J Clin Psychopharmacol.
200626600-609.
62Olanzapine-fluoxetine CombinationTreatment for
Bipolar I Depression
Source
Review
0
Placebo (N 355)
-2
Olanzapine (N 351)
-4
OFC (N 82)
-6
Reviewer Memo
-8
Improvement
MADRS Change From Baseline
-10
-12
-14
-16
-18
-20
0
1
2
3
4
5
6
7
8
Week
P lt 0.05 olanzapine vs placebo P lt 0.05 vs OFC
N 788 Tohen M, et al. Arch Gen Psychiatry.
2003601079-1088.
Slide Modified
Memo
63Comparison of Olanzapine and Olanzapine-Fluoxetin
e in Bipolar I Depression MADRS Items
Apparent sadness
OFC (n 82)
Placebo (n 355)
Reported sadness
Olanzapine (n 351)
Inner tension
Reduced sleep
Reduced appetite
Concentration difficulties
Lassitude
Inability to feel
Pessimistic thoughts
Suicidal thoughts
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
OFC olanzapine fluoxetine N 788 P lt 0.05
vs placebo P lt 0.05 vs olanzapine Week 8
assessment
Mean Change From Baseline in MADRS score
Tohen M, et al. Arch Gen Psychiatry.
2003601079-1088.
64TIMA Guidelines for Maintenance Treatment Most
Recent Episode Depressed
- It is an option to remain on well-tolerated,
effective, acute-phase treatments - Available evidence supports the options presented
for maintenance treatment
Patients With Recent and/or Severe History of
Mania
Lamotrigine Combined With Antimanic Agent
Level I
All Other Patients
Lamotrigine Monotherapy
Level II Lithium
Level III Combination of Antimanic and
Antidepressant That Has Been Effective in the
Past, including Olanzapine/Fluoxetine
Combination1
Level IV Valproate, Carbamazepine,
Aripiprazole,2 Clozapine,1 Olanzapine,1
Quetiapine,2 Risperidone,2 Ziprasidone2
Level V Typical Antipsychotics,1
Oxcarbazepine,2 ECT
1. Safety issues warrant careful consideration of
this option for potential long-term use 2.
Relatively limited information is currently
available on this agent in long-term use
Suppes T, et al. J Clin Psychiatry.
200566870-886.
65Maintenance Treatment
- FDA-indicated agents
- Lithium
- Lamotrigine
- Olanzapine
- Aripiprazole
Physicians Desk Reference. 61st ed. Montvale,
NJ Medical Economics Co 2007.
66Lithium vs Placebo in Maintenance
1.2
Lithium
1
Placebo
0.8
0.6
Probability of Remaining Well
0.4
0.2
0
0
10
20
30
40
50
60
Follow-Up (weeks)
Keck PE Jr, et al. Biol Psychiatry.
200047756-761.
67Lithium Reduces Mortality
Cochrane Controlled Trials Registry 32
Randomized Trials 1389 patients randomized to
lithium 2069 randomized to active comparators
Cipriani A, et al. Am J Psychiatry.
20051621805-1819.
68Lamotrigine or Placebo Time to Intervention for
Any Mood Episode Combined Analysis
70 60 50 40 30 20 10 0
100 90 80 70 60 50 40 30 20 10 0
Lamotrigine 100-400 mg (n 223) Placebo (n 188)
37
of patients
22
Estimated of Pts Intervention-Free
18 months
LTG vs PBO, P lt 0.001
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Month
Goodwin GM, et al. J Clin Psychiatry.
200465432-441.
69Lamotrigine or Placebo Time to Intervention for
a Depressive EpisodeCombined Analysis
70 60 50 40 30 20 10 0
57
41
of patients
18 months
Some patients considered intervention-free for
depressive episodes could have had intervention
for manic episodes.
Goodwin GM, et al. J Clin Psychiatry.
200465432-441.
70Lamotrigine or Placebo Time to Intervention for
a Manic Episode Combined Analysis
70 60 50 40 30 20 10 0
65
100 90 80 70 60 50 40 30 20 10 0
53
Lamotrigine 100-400 mg (n 223) Placebo (n 188)
of patients
Estimated of Pts Intervention-Free
18 mo
LTG vs PBO, P 0.034
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Month
Some patients considered intervention-free for
manic episodes could have had intervention for
depressive episodes.
Goodwin GM, et al. J Clin Psychiatry.
200465432-441.
71Maintenance Treatment Atypical Antipsychotics
- Olanzapine is recommended as an alternate
first-line therapy - Aripiprazole is recommended as a second-line
therapy - Other atypical antipsychotics (quetiapine,
risperidone, ziprasidone) are potential
maintenance treatments
Suppes T, et al. J Clin Psychiatry.
200566870-886. Yatham LN, et al. Bipolar
Disord. 200575-69.
72Olanzapine Versus Placebo Relapse Into Mania or
Depression
1.0
1.0
0.8
0.8
0.6
0.6
Probability of Remaining Relapse Free
0.4
0.4
Subjects receiving olanzapine (N 225)
Subjects receiving olanzapine (N 225)
0.2
0.2
Subjects receiving placebo (N 136)
Subjects receiving placebo (N 136)
0.0
0.0
0
50
100
150
200
250
300
350
400
50
100
150
200
250
300
350
400
0
Days to Relapse Into Mania Only
Days to Relapse Into Depression Only
P lt 0.001
P lt 0.001
Tohen M, et al. Am J Psychiatry. 2006163247-256.
73Aripiprazole for Maintenance Treatment of
Bipolar Disorder
Manic Relapse
Depressive Relapse
1.0
1.0
0.9
0.9
0.8
0.8
0.7
0.7
0.6
Proportion of Patients Without Relapse
0.6
Proportion of Patients Without Relapse
0.5
0.5
0.4
0.4
0.3
0.3
0.2
0.2
Aripiprazole (N 77) Placebo (N 83)
Log rank P 0.008 HR 0.309 (95 CI 0.123 to
0.774)
Aripiprazole (N 77) Placebo (N 83)
Log rank P 0.683 HR 0.833 (95 CI 0.345 to
2.011)
0.1
0.1
0.0
0.0
0
28
56
84
112
140
168
196
28
56
84
112
140
168
196
0
Days in Study
Days in Study
Keck PE Jr, et al. J Clin Psychiatry.
200667626-637.
74Maintenance Treatment Antidepressants
- Maintenance antidepressants efficacy has been
established in unipolar but not bipolar
depression - Increased cycling on antidepressants has been
shown in three placebo-controlled studies - Not recommended, but if used, must be used with
an antimanic agent in bipolar I disorder - When antidepressants are used in acute therapy,
taper and discontinue them after recovery from
depression maintain them only in those who
repeatedly relapse soon after discontinuation
(about 20 of bipolar patients)
Ghaemi SN, et al. Bipolar Disord.
20035421-433. Suppes T, et al. J Clin
Psychiatry. 200566870-886. Yatham LN, et al.
Bipolar Disord. 200575-69.
75Maintenance Treatment Anxiolytics
- Systematic evaluation of benzodiazepines as
prophylactic agents in bipolar disorder has not
been conducted - Issues such as dependence, rebound anxiety,
memory impairment argue against their long-term
use
Yatham LN, et al. Bipolar Disord. 200575-69.
76Maintenance Treatment Mood Stabilizer
Combinations
- Some efficacy demonstrated
- Lithium plus valproate
- Lithium plus carbamazepine
- Olanzapine-fluoxetine combination has shown
efficacy - Many other combinations are used but with limited
evidence
Suppes T, et al. J Clin Psychiatry.
200566870-886. Yatham LN, et al. Bipolar
Disord. 200575-69.
77Relapse Prevention
- Features associated with increased risk of
recurrence - 20 previous episodes of depression or
(hypo)mania - Residual manic symptoms at response
- More days depressed/anxious in previous year
associated with depressive recurrence - More time spent in manic/hypomanic state in past
year associated with shorter time to
manic/hypomanic/mixed episode recurrence - Suggests bipolar disorder remains a highly
recurrent, predominantly depressive illness - Targeting residual symptoms in maintenance
treatment may reduce risk of recurrence
Perlis RH, et al. Am J Psychiatry.
2006163217-224.
78The Importance of Subsyndromal Symptoms in
Bipolar Disorder
- Subsyndromal (subthreshold) symptoms (those that
fail to meet full diagnostic criteria for mood
episode) are a significant public health issue - May be related to poor outcomes
- Are associated with deficits in social and
occupational functioning - Increase the risk of relapse
- Are significantly associated with functional
impairment in multiple domains
Altshuler LL, et al. J Clin Psychiatry.
2006671551-1560. Marangell LB. J Clin
Psychiatry. 200465(suppl 10)24-27.
79Subsyndromal Symptoms Are Associated With
Functional Impairment in Over 5075 of Patients
Altshuler LL, et al. J Clin Psychiatry.
2006671551-1560.
80Treating Subsyndromal Mood Symptoms in Bipolar
Disorder Evaluation of Maintenance Trials
- Two 18-month, randomized, placebo-controlled
maintenance trials for bipolar I disorder were
evaluated for incidence, time course, impact of
pharmacotherapy on subsyndromal symptoms - Subsyndromal symptoms occurred in 25 of all
visits - Compared with placebo (54.8), higher mean
percentage of visits in remission with
lamotrigine (63.0, P .020) but not with
lithium (60.0, P 0.165) - Lithium and lamotrigine delayed onset of
subsyndromal symptoms and time from onset of
relapse - Further studies are needed to assess whether
treatment interventions can minimize subsyndromal
symptoms or prevent relapse
Frye MA, et al. J Clin Psychiatry.
2006671721-1728.
81Treatment-Resistant Bipolar Depression STEP-BD
25
- Open randomized trial
- Prior nonresponse to MS AD
- LTG 150250 mg/day
- INO 1025 gms/day
- RIS up to 16 mg/day
- Up to 16 weeks
- Recovery lt 2 sxs
- for 2 mos
20
15
Recovery Rate ()
10
5
0
Lamotrigine (N 21)
Inositol (N 23)
Risperidone (N 23)
Nierenberg AA, et al. Am J Psychiatry.
2006163210-216.
82Recommendations for Combination Therapy in
Bipolar Disorder
- Combination therapy is the rule, not the
exception - Use evidence-based data when available
- Add drugs to the treatment regimen that
specifically targets residual symptoms
Bowden CL. J Clin Psychiatry. 200465(suppl
15)21-24.
83Take Home Messages
- Goal is to stabilize depression without causing
mania and minimizing side effects - Monotherapy antidepressants can destabilize
bipolar depression - Evidence-based treatment for bipolar depression
includes lithium and lamotrigine - Quetiapine is the only approved monotherapy for
bipolar depression - OFC is the only FDA approved combination therapy
for bipolar depression - Some novel antipsychotics may have a role in
treating bipolar depression as monotherapy while
stabilizing mania
84Section 4 Nonpharmacologic Treatment Approaches
85Goals of Psychotherapy
- Establish and maintain a therapeutic alliance
- Provide education about the disease and its
treatment - Promote regular patterns of activity and sleep
- Identify cognitive distortions linked with
depression - Identify sources of interpersonal discord (eg,
expressed emotion) and promote healthy responses
to stress - Detect early warning signs of mood episodes
- Minimize the negative impact of the illness
- Promote the regular use of medications
86Enhancement of Adherence and Improving Illness
Outcome in Bipolar Disorder
- Patients with bipolar disorder are often poorly
adherent to their medical regimens - While psychotherapy for bipolar disorder is known
to generally improve illness outcome, it has been
reported that interventions that focus on
treatment adherence may yield positive results in
this specific area
Cochran SD. J Consult Clin Psychol.
198452873-878. Colom F. Bipolar Disord.
20024(suppl 1)102.
87Psychosocial Treatment Options
- Brief technique-driven interventions 6 to 12
individual sessions - Cognitive therapy
- Interpersonal social rhythm therapy (IPSRT)
- Family or couples therapy
- Group psychoeducation
Scott J, et al. Psychiatr Clin North Am.
200528371-384.
88Evidence-Based Therapies
- Impact on relapse and rehospitalization rates
- Group psychoeducation
- 25 hospitalized vs 35 in unstructured group1
- Cognitive behavioral therapy (CBT)
- 1 year relapse 44 vs 75 usual care2
- 2-year follow-up found no reduction in relapse
rates after first 6 months 3 - Family focused treatment (FFT)
- 2 year relapse 28 with FFT vs 60 with
individual support4 - Perceived criticism may be an indicator 5
1. Colom F, et al. Arch Gen Psychiatry.
200360402-407. 2. Lam DH, et al. Arch Gen
Psychiatry. 200360145-152. 3. Lam DH, et al. Am
J Psychiatry. 2005162324-329. 4. Rea MM, et al.
J Consult Clin Psychol. 200371482-492. 5.
Miklowitz DJ, et al. Psychiatry Res.
2005136101-111.
89Interpersonal Social Rhythm Therapy Focus
- IPSRT focuses on
- The link between mood and life events
- The importance of maintaining regular daily
rhythms - The identification and management of potential
precipitants of rhythm dysregulation with
attention to interpersonal triggers - The identification and management of affective
symptoms
Frank E, et al. Biol Psychiatry. 200048593-604.
90Benefits of Psychotherapy Interventions
- Adjustment to Dx and Rx
- Enhanced adherence
- Improved self-esteem
- Reduced risky behaviors
- Modification of destabilizing biopsychosocial
factors - Management of stressors
- Learning coping strategies
- Early recognition
- Modification attitudes/beliefs
Scott J, Gutierrez MJ. Bipolar Disord.
20046498-503.
91Psychotherapy Reduces Relapse Rate
0.1
1
10
1
Logarithmic scale of odds ratio
Favors therapy
Significant reduction in relapse rate (40)
compared to standard treatment alone.
Scott J, et al. Intl J Neuropsychopharmacol.
200710123-129.
92Section 5 Use of Antidepressants in Bipolar
Disorder
93Treatment of Bipolar Depression
- Fewer studies than for mania
- Limited approved treatments
- Antidepressants lack evidence and may cause mood
destabilization
Ghaemi SN, et al. J Clin Psychiatry.
200162565-569. Ghaemi SN, et al. Am J
Psychiatry. 2004161163-165.Muzina DJ,
Calabrese JR. Int J Neuropsychopharmacol.
20036285-291.
94Use of Antidepressants in Bipolar Disorder
- Bipolar disorder is associated with considerable
depressive morbidity - Risk-to-benefit ratio of antidepressants as
adjuncts to mood stabilizers is an area of
controversy and disagreement - Antidepressants may increase risk of iatrogenic
mania, mixed states, rapid cycling - APA 2002 guidelines recommend conservative use of
antidepressants - Although evidence of their safety and efficacy is
limited, antidepressants are commonly used in
treatment of bipolar depression
Hirschfeld RM et al. Presented at 156th American
Psychiatric Association Annual Meeting May
17-22, 2003 San Francisco, CA. Goldberg JF, et
al. Bipolar Disord. 20035407-420. American
Psychiatric Association. Practice Guidelines for
the Treatment of Patients With Bipolar Disorder.
2nd ed. Washington, DC American Psychiatric
Publishing Group 2002.
95Bipolar Depression and AntidepressantsGeneral
Clinical Guidelines and Risks
- Conservative approach to antidepressant use
- Risk of antidepressant induced mood-cycling in
about 1530 of patients - Mood stabilizers (lithium, lamotrigine) are
effective in acute and prophylactic treatment of
depression lithium is effective in suicide
prevention - Antidepressants should be reserved for severe
cases of acute bipolar depression and not used
routinely - Cost/risk benefit ratio for antidepressant
treatment of bipolar depression is unfavorable - Antidepressants should be discontinued after
recovery from depressive episode (mixed evidence
for this recommendation)
- American Psychiatric Association. Practice
Guidelines for the Treatment of Patients With
Bipolar Disorder. 2nd ed. Washington, DC
American Psychiatric Publishing Group 2002. - Ghaemi SN, et al. Bipolar Disord. 20035421-433.
- Ghaemi SN, et al. Am J Psychiatry.
2004161163-165.
96No Antidepressant Advantage For Paroxetine or
Imipramine If Lithium Levels Are Therapeutic
N 15 15 14 7 10 7
60
P NS
P 0.05
50
40
Responders per Hamilton Criterion 7
Li PBO
30
Li PAR
Li IMI
20
10
Switch Rates LiPBO 2.3 LiIMI 7.7 LiPAR 0
0
Overall Efficacy
Li 0.8 mEq/L
PBO Placebo PAR Paroxetine IMI Imipramine
Nemeroff CB, et al. Am J Psychiatry.
2001158906-912.
97Antidepressant Efficacy Stanley Network
N 32 42 37 15 22
22
68.8
71.0
62.5
55.3
With CGI 1 or 2
48.5
43.0
Leverich GS, et al. Am J Psychiatry.
2006163232-239.
98Time Until Switch With Antidepressants Stanley
Bipolar Network
1.0
0.8
P 0.03
0.6
Cumulative Proportion Without a Switch
0.5
0.2
Patients with bipolar I disorder (N 115)
Patients with bipolar II disorder (N 44)
Censored
0.0
200
300
100
400
500
0
Time to Switch (days)
Leverich GS, et al. Am J Psychiatry.
2006163232-239.
99Ratio of Threshold Switches to Subthreshold Brief
Hypomanias
4.0
More Threshold Than Subthreshold Phenomena
3.5
3.0
2.5
Ratio of Threshold Switches to Subthreshold Brief
Hypomanias
2.0
1.5
1.0
More Subthreshold Than Threshold Phenomena
Bupropion
0.5
Sertraline
Venlafaxine
0.0
Acute Antidepressant Trials (10 weeks)
Continuation Antidepressant Trials ( 1 year)
Leverich GS, et al. Am J Psychiatry.
2006163232-239.
100Maintenance Antidepressants in Bipolar Disorder
- Maintenance antidepressants efficacy has not been
established in bipolar disorder - Increased cycling on antidepressants has been
shown in three placebo-controlled studies - When antidepressants are used in acute therapy,
taper and discontinue them after recovery from
depression - Maintain antidepressants only in those who
repeatedly relapse soon after discontinuation
(about 20 of bipolar patients)
Ghaemi SN, et al. Bipolar Disord. 20035421-433.
101TIMA 2005 Bipolar Acute Depression
Stage 1
OtherAntimanic
No Antimanic, Severe or Recent Mania
No Antimanic,No Severe or Recent Mania
Taking Li
(Increase Li to 0.8 mEq/L)
(continue)
Antimanic Lamotrigine
Lamotrigine
- Lamotrigine is a mood stabilizer not antimanic
- Lithium is an antimanic
- If history of recent or severe mania, add or
optimize antimanic - Otherwise, lamotrigine monotherapy may be
appropriate
Suppes T, et al. J Clin Psychiatry.
200566870-886.
102TIMA 2005 Bipolar Acute Depression
Partial Response or Nonresponse
Stage 2
Quetiapine or Olanzapine-Fluoxetine
Response
Partial Response or Nonresponse
CONT
Stage 3
Combination from Li, LTG, QTP, or OFC
- Designed to minimize cycle risk
- Note no anticonvulsant except LTG until Stage 4
- Overlap and taper
- Follow ADA guidelines regarding metabolic
monitoring
Suppes T, et al. J Clin Psychiatry.
200566870-886.
103TIMA 2005 Bipolar Acute Depression
Response
CONT
Partial Response Or Nonresponse
Li, LTG, QTP, OFC, VPA, or CBZ SSRI, BUP, or
VEN or ECT
Stage 4
- Combinations (OFC combinations 3 drugs)
- Lamotrigine should not be combined with AD
without antimanic - Includes VPA and CBZ at this point
- SSRIs include CTP, FLX, PRX, SRT, and FLV
- Some advocate the use of AD earlier but
evidence is lacking - Venlafaxine associated with more mania
induction
BUP bupropion CBZ carbamazepine CTP
citalopram ECT electroconvulsive therapy Li
lithium LTG lamotrigine OFC
olanzapine-fluoxetine combination QTP
quetiapine SSRI selective serotonin reuptake
inhibitor VEN venlafaxine VPA
valproate Suppes T, et al. J Clin Psychiatry.
200566870-886.
104Bipolar Depression and Antidepressants General
Guidelines and Risks
- Always use mood stabilizer in bipolar I patients,
even while depressed - Promptly wean the antidepressant if evidence of
hypomania or mania emerges - Antidepressants may trigger mania (mood
destabilization) or accelerate mood cycle - Up to 33 of patients with bipolar disorder may
be susceptible to antidepressant-induced manias - Possibly less efficacious in bipolar than
unipolar depression - Few standard antidepressants have been studied in
bipolar depression
Dantzler A, Osser DN. Psychiatr Ann.
199929270-284. Frances AJ, et al. J Clin
Psychiatry. 199859(suppl 4)73-79. Goldberg JF,
Ernst CL. J Clin Psychiatry. 200263985-991. Gold
berg JF, Truman CJ. Bipolar Disord.
20035407-420. Möller HJ, et al. J Affect
Disord. 200167141-146.
105Complicated Bipolar Relapse
106Presentation
- 32-year-old female
- Brought to ER by police
- Family called 911 after altercation at
- home escalated
107History of Present Illness
- Sister tells ER doctor that patient has been
getting more irritable for last 6 weeks - Missed outpatient psychiatrist appointment 2
weeks ago - Spent disability check and couldn't afford to
fill prescription - Sister suspects patient has started abusing
cocaine again
108Past Psychiatric History
- Diagnosed with bipolar disorder at age 21
- 5 prior hospitalizations (3 manic episodes, 2
depressive episodes with suicidality) - Sporadic outpatient attendance with partial
medication - compliance
- Responded to lithium, but patient discontinued
due to - tremor
- Responded to valproic acid, but patient
discontinued - due to weight gain
- Noncompliance associated with cocaine abuse
109Recent Psychiatric History
- More irritable
- Feels her sister is checking on her too much
- Feels she can make a new start and called
- CNN and NBC seeking audition as newscaster
- Poor sleep pattern
110Past Medical History
- Hypertension
- Obesity (BMI 32)
- Gallstone surgery
111Social and Family History
- Social History
- Cigarette smoker
- 2 DUIs
- On disability for bipolar disorder
- Family History
- Mother has bipolar disorder
- First cousin committed suicide
- Patient has longstanding difficulties in her
family relationship - Divorced twice
- 1 child has ADHD, 1 cousin with bipolar disorder
112Mental Status Examination
- Intoxicated and irritable in ER
- Angry with her sister, vague threats (she
better - watch out if she continues to be so pushy)
- Speech pressured
- Tells ER doctor she doesn't want to be
hospitalized because she is setting up interview
with CNN - If she doesn't get the job, it will be over
113Differential Diagnosis
- Bipolar disorder, manic relapse
- Polysubstance abuse
114Laboratory Tests
- Urinary drug screen positive for cocaine,
benzodiazepines - Pregnancy test negative
- Glucose and triglycerides normal
- Cholesterol mildly elevated
- Liver function tests normal
115Clinical Course
- Initially refuses admission and becomes
- belligerent in ER
- Calmed by intramuscular (IM) injection of
- antipsychotic
- Later on required a second IM injection and
admitted to the hospital - Still irritable, pressured in speech, and
sleeping - 3 hours a night
- Quetiapine started with gradual titration to
- 600 mg/day
116Clinical Course (cont)
- Patient decided to try lithium monotherapy for
outpatient care - Becomes more agreeable and engaged in treatment
- Reluctantly agrees to aftercare substance abuse
day program - Says she'll take her medications but that "they
better not make me fatter"
117Case Summary
- Female with dual diagnosis bipolar disorder I
- Cardiovascular/weight comorbidities
- Intermittent noncompliance and substance abuse
underlie poor long-term course and heightened
risk of injurious behavior - Doctor's capacity to achieve persistent clinical
stability strongly influenced by patient's
perceived effectiveness (risk versus benefit
appraisal) of medications
118Key Messages
- Therapeutic engagement is a critical first step
to treatment adherence - Careful assessment of
- Medical and psychiatric comorbidities in bipolar
disorder - Treatment options (agents, formulations) in
managing acutely agitated bipolar patients - Treatment goals (choice agents, risk-benefit
appraisal) in stabilization of bipolar patients - Treatment priorities, decisions, and transition
to outpatient maintenance therapy
119The Bland Chef
120History
- 37-year-old single female, without children,
employed as a chef at a local hotel - Chief complaint Im depressed and wired
- Diminished interest in her work, which she
previously was passionate about - No suicidal ideation
- Hyperphagia, hypersomnia, racing thoughts, feels
anxious and hyper, irritable with friends,
severe premenstrual worsening - Mood instability admixed with nonrefreshing
sleep, led to previous diagnosis of major
depression
121History of Present Illness
- Current episode began approximately six months
ago in the absence of identifiable interpersonal
stressors - Confluence of depressive symptoms, increasing
severity - Has noted decreased sleep by approximately 12
hours on occasion my mind wont stop when my
head hits the pillow - Has noted panic attacks, generalized anxiety, and
mood lability woven into depressive symptoms, no
suicidal ideation, psychotic features, alcohol or
substance abuse
122History of Present Illness (cont)
- Although patient maintains normal working hours,
spends less time creating new menu items - On days off, has been exercising less and
becoming socially withdrawn - Current antidepressant, an SSRI, offers minimal
symptom relief and may even worsen my anxiety - Adherent with medication prescribed 8 weeks ago
123Past Psychiatric History
- Recalls being anxious as a child
- No externalizing behavioral disorder or history
of trauma - Index depressive episode as sophomore, age 21
after breakup with boyfriend - Depressive episodes typically last 24 months in
duration with suggestion of worsening in the fall
124Past Psychiatric History (cont)
- Has received three previous antidepressants, all
of which she described as not working - Further history reveals that previous
antidepressants worsened anxiety - Has been in therapy on one previous occasion for
three months, but my therapist didnt understand
me - Occasionally takes benzodiazepines when agitation
is severe - No prior hospitalization
125Recent Psychiatric History
- Prior to onset of current depression, patient was
awarded Chef of the Yea