Challenges and Clinical Aspects of Diagnosing Bipolar Disorder

1

• Section 1
• Challenges and Clinical Aspects of Diagnosing
  Bipolar Disorder

2
Various Phases of Bipolar Disorder
Mania
Hypomania
Euthymia
Polarity of Symptoms
Subsyndromal Depression
Depression
Depression
Adapted from Stahl SM. Essential
Psychopharmacology. New York, NY Cambridge
University Press 2000.
3
Symptom Domains of Bipolar Disorder
Dysphoric or Negative Mood and Behavior
Manic Mood and Behavior

• Euphoria
• Grandiosity
• Pressured speech
• Impulsivity
• Excessive libido
• Recklessness
• Social intrusiveness
• Diminished need for sleep

• Depression
• Anxiety
• Irritability
• Hostility
• Violence
• Suicide

BIPOLARDISORDER
Thought/Cognitive Dysfunction
Psychotic Symptoms

• Racing thoughts
• Distractibility
• Disorganization
• Inattentiveness

• Delusions
• Hallucinations

Slide courtesy of Keck PE Jr. adapted from
Goodwin FK, Jamison KR. Manic-Depressive Illness.
Oxford University Press New York, NY 1990.
4
Spectrum of Bipolar Disorders

• Bipolar I
• Bipolar II
• Hypomania
• Cyclothymia
• NOS
• 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.
5
Bipolar Terminology

• Mania
• A distinct period of abnormally and persistently
  elevated, expansive, or irritable mood, lasting
  at least 1 week with a significant decline in
  function
• Hypomania
• A distinct period of persistently elevated,
  expansive, or irritable mood, lasting at least 4
  days, that is clearly different from the usual
  non-depressed mood, without a significant decline
  in function

• Young LT. J Psychiatry Neurosci 20042987-88.
• American Psychiatric Association Diagnostic and
  Statistical Manual of Mental Disorders, Fourth
  Edition, Text Revision. Washington, DC American
  Psychiatric Association 2000.

6
Bipolar Terminology (cont)

• Mixed Episode
• The criteria are met both for a manic episode and
  for a major depressive episode
• 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

• Young LT. J Psychiatry Neurosci. 20042987-88.
• American Psychiatric Association Diagnostic and
  Statistical Manual of Mental Disorders, Fourth
  Edition, Text Revision. Washington, DC American
  Psychiatric Association 2000.

7
Diagnosis of Bipolar DepressionChallenges and
Strategies

• Bipolar depression is frequently misdiagnosed as
  unipolar depression
• Patients focus on periods of depression and often
  neglect to report periods of elevated mood
• Various techniques have been identified to
  increase diagnostic accuracy

8
Complexities of Diagnosing Bipolar Disorders

• Psychotic symptoms also occur in mood disorders
• Substance abuse is very common and complicates
  diagnosis
• Depression is more common in bipolar disorder
  than any other mood episode
• Bipolar patients spend more time depressed than
  manic
• Depression may be first manifestation of a
  bipolar disorder

Judd LL, et al. Arch Gen Psychiatry.
200259530-537. Gao K, Calabrese JR. Bipolar
Disord. 2005713-23. Swann AC, et al. Prim Care
Companion J Clin Psychiatry. 2005715-21.
9
High Rate of Misdiagnosis

• Retrospective, single site study, N 85
• 37 of patients were misdiagnosed with unipolar
  depression even though they had seen a mental
  health professional after their first
  manic/hypomanic episode
• 810 years from onset to treatment for bipolar
  disorder
• Due to the above, antidepressants were used
  earlier and with 23 experiencing a new or
  worsening rapid-cycling course

Ghaemi SN, et al. J Clin Psychiatry.
200061804-808.
10
Screening ToolsThe 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.
11
Screening ToolsThe Mood Disorder Questionnaire
(cont)

• The Mood Disorder Questionnaire
• Derived from DSM-IV criteria and clinical
  experience
• Initial validation study of MDQ in psychiatric
  outpatients
• (N 198)
• Sensitivity 73 and Specificity 90 for
  Bipolar I and II
• Validation study of MDQ in general population (N
  711)
• Sensitivity 28 and Specificity 97 for
  Bipolar I and II
• MDQ as screening tool (13 questions)
• Positive MDQ ? 7 yes responses Negative MDQ ?
  7 yes responses
• Rapid screening tool 10 minutes or less
• Patients can self-administer MDQ while in the
  waiting area
• Does not require trained evaluators

Hirschfeld RM, et al. J Clin Psychiatry.
20036453-59.
12
Bipolar Disorder Diagnosis Is Often Missed

• Positive screen rate for bipolar illness 3.7 (gt
  6 million people in US)
• 66.8 response rategt 85,000 US Adults Surveyed

3.7
Bipolar Dx 19.8
No Bipolar Dx 80.2
96.3
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.
13
Prior Physician Diagnoses AmongMood Disorder
Questionnaire Positives forBipolar Disorder in
the Community
Diagnosed withbipolar disorder
N 85,358 subjects
20
Neither bipolar disorder nor depression diagnosis
49
31
Diagnosed with depressionbut not bipolar disorder
80 of patients who screened positivefor BP had
not been diagnosed with BP
Hirschfeld RMA, et al. J Clin Psychiatry.
20036453-59.
14
Misdiagnosis of Bipolar Disorder

• 2000 NDMDA Initial Diagnosis (69)

NDMDA National Depressive and Manic-Depressive
Association N 400 Hirschfeld RM, et al. J Clin
Psychiatry. 200465(suppl 15)5-9.
15
Still No Improvement in Diagnosis and Treatment
of Bipolar Disorder

• NDMDA Survey, 1994
• 73 reported at least one incorrect diagnosis
• 3.3 physicians and 8 years till correct diagnosis
• 59 onset in adolescence or childhood
• gt 50 received no assistance for 5 years
• 27 response rate
• NDMDA Survey, 2000
• 69 misdiagnosed (mostly unipolar)
• Those misdiagnosed consulted an average of 4
  physicians prior to correct diagnosis
• 810 years from onset to treatment
• 66.8 response rate

Lish JD, et al. J Affect Disord.
199431281-294. Hirschfeld RM, et al. JAMA.
1997277333-340. Hirschfeld RM, et al. J Clin
Psychiatry. 200364161-174.
16
Bipolar Disorder Is Frequently Misdiagnosed

• Only 1 in 5 patients with bipolar disorder is
  correctly diagnosed by a physician
• Those incorrectly diagnosed were more likely to
  be female, poorer, and have greater impairment
• Delay of treatment may reduce the efficacy of
  certain pharmacological agents (eg, lithium)
• 1 in 3 is misdiagnosed as having unipolar
  depression, perhaps due to the prevalence of the
  depressive phase of the illness

Data based on MDQ positive scores, not clinical
diagnosis of bipolar disorder. Hirschfeld RM, et
al. J Clin Psychiatry. 20036453-59.
17
Delay in Treatment of Bipolar I and II

• National Comorbidity Survey (NCS) Replication
• Treatment contact in year of onset only 39.1
• Median duration of delay in treatment 6 years
• 90.2 eventually make contact (projection)
• No significant differences among affective
  disorders
• Predictors of delay and failure
• Cohort of gt 59 years less likely to make contact
  than lt 30 years
• Onset age 1319 years more likely than onset ? 30
• Males more likely than females

Wang PS, et al. Arch Gen Psychiatry.
200562603-613.
18
Long-term Frequency of Depressive Symptoms
Weeks Symptomatically Ill (47)
Depressed (68)
Mixed States (13)
Weeks Asymptomatic (53)
Manic/Hypomanic (19)

• Depressive symptoms were predominant
• Depression was 3.5-fold more frequent than mania
• 90 of patients had at least 1 week of depressive
  symptoms
• Depression (but not mania) predicted greater
  future illness burden

Patients with bipolar I disorder experienced mood
symptoms nearly half of the time during a
12.8-year follow-up period.
Judd LL, et al. Arch Gen Psychiatry.
200259530-537.
19
Time Spent Depressed Bipolar I vs Bipolar II

• NIMH Collaborative Study, 13 years
• Bipolar I
• Depressionmania 31
• Bipolar II
• Depressionmania 371
• Higher morbidity, chronicity

50.3
31.9
Percent of Weeks
9.3
1.3
BP I 31 (N 146)
BP II 371 (N 71)
Judd LL, et al. Arch Gen Psychiatry.
200259530-537. Judd LL, et al. Arch Gen
Psychiatry. 200360261-269.
20
Bipolar Depression Significantly Disrupts
Patients Lives
30.1
Bipolar Unipolar Control
Work
13.3
1.1
42.1
Social Life
19
2.3
43.9
Family Life
19.9
2.5
0
10
20
30
40
50
100
of Patients With Marked or Extreme Disruption 4
Weeks Prior to Survey
P lt 0.0001 among groups for each dimension
Self-administered nationwide epidemiological
survey of 2,801 respondents bipolar depressed
(N 395) defined by a positive screen on the MDQ
or report of physician-diagnosed bipolar
disorder/bipolar depression Unipolar depressed
(N 794) defined by positive screen for
depression or report of physician-diagnosed
depression but not bipolar disorder. Hirschfeld
RM et al. Presented at 156th American
Psychiatric Association Annual Meeting May
17-22, 2003 San Francisco, CA.
21
Manic/Hypomanic Episodes May Not be Recognized
by the Patient

• Patients who experience mania often deny elevated
  mood
• Denial of elevated mood during an evaluation may
  eliminate bipolar disorder from the diagnosis
• Patients are better at recalling behavioral
  aspects to hypomania/mania
• Patients can then identify the abnormal mood
• MDQ effective at identifying manic/hypomanic
  episodes

22
Underrecognition of Hypomania by the Physician
Diagnosis at Visit 1(Strict DSM-IV criteria)
Diagnosis at Visit 2(Broader Systematic Criteria)
BP I/II (or Pseudo-UP)9
Unipolar45
Unipolar72
BP II22
BP II40
BP I6
BP I6
Hantouche EG, et al. J Affect Disord.
199850163-173.
23
Psychiatric Comorbidities Occur Frequently and
Can Complicate Diagnosis of Bipolar Disorder

• 65 of bipolar patients have current axis I
  condition
• Nearly 25 have 3 or more
• Substance abuse (lifetime prevalence 61) and
  anxiety disorders (lifetime prevalence 42) are
  most common
• Comorbid conditions can mimic mood symptoms, mask
  them, or exacerbate them

McElroy SL, et al. Am J Psychiatry.
2001158420-426.
24
Lifetime Comorbid Axis I Diagnoses in Bipolar
Patients
Percent
McElroy SL, et al. Am J Psychiatry.
2001158420-426.
25
Mood-Congruent Psychotic (MCP) vs
Mood-Incongruent Psychotic (MIP) Distinction in
Mania

• French National Study, N 1090
• 33.4 psychotic symptoms in mania are mood
  congruent and 16.5 were mood incongruent
• MIP patients had been significantly more often
  diagnosed as schizophrenic, or having anxiety
  disorders, with long delays to first diagnosis as
  bipolar disorder
• MIP patients were also significantly different in
• 21 female/male ratio
• Shorter free intervals between episodes
• More auditory hallucinations
• Persecutory and somatic delusions
• Higher depression scores
• Anxious and hyperemotionality

Azorin JM, et al. J Affect Disord. In press.
26
Implications of Inappropriate Treatment
Lifetime Risk of Developing Mania/Hypomaniaor
Rapid Cycling While Taking Antidepressants

• Naturalistic chart review of 85 depressed
  patients
• 56 misdiagnosed as unipolar depression
• Antidepressants used earlier and more often than
  mood stabilizers
• Naturalistic study of 38 patients with bipolar
  disorder in a psychiatric clinic misdiagnosed and
  (mis)treated as having unipolar depression

100
N 38
80
55
60
Patients ()
40
23
20
0
Mania/Hypomania
RapidCycling
Ghaemi SN, et al. J Clin Psychiatry.
200061804-808.
27
Diagnostic Presentation by Age

• Bipolar patients who are approximately lt 50 years
  old at first psychiatric hospitalization present
  more with psychotic manic episodes
• Bipolar patients who are approximately gt 65 years
  old more often present at first psychiatric
  hospitalization with severe depressive episodes
  with psychosis

Kessing LV. Bipolar Disord. 2006856-64.
28
Clinical Differences Unipolar vs Bipolar

• Bipolar depression was associated with bipolar
  family history
• Earlier age of onset
• Greater number of previous depressive episodes
• Fears were more common in bipolar depression
• Atypical features
• Loss of pharmacotherapeutic response during
  antidepressant treatment
• Cycle acceleration with antidepressant treatment

Perlis RH, et al. Am J Psychiatry.
2006163225-231. Ghaemi SN, et al. Am J
Psychiatry. 2004161163-165.
29
Bipolar vs Unipolar Depression

• Reversed Vegetative Features 5 Times More Common

Bipolar
Unipolar
Consecutive
Loaded pedigree
Bipolar FHx
1-2 wks AD use
Chronic
Postpartum
Psychosis
Hypersomnia/ Psychomotor Retardation
0
10
20
30
40
50
60
Percent
Akiskal HS, et al. J Affect Disord.
19835115-128.
30
Summary

• Bipolar disorder has a high prevalence in the
  general population (nearly 4 in the MDQ
  community survey)
• A significant proportion of unipolar depression
  represents undiagnosed bipolar disorder
• Bipolar depression has serious functional
  outcomes
• More impairment than mania
• More severe and more impairing than unipolar
  depression

31
Summary (cont)

• Misdiagnosis can result in inappropriate
  treatment, aggravated course, and future
  treatment resistance
• Utilizing screening tools, such as the MDQ, can
  help differentiate bipolar disorder from unipolar
  depression and decrease the risk of misdiagnosis
  and/or delayed diagnosis
• Characteristics of bipolar depression include
  early age of onset, anxiety, fatigue, and reverse
  vegetative signs and symptoms