1. Recognition and Diagnosis of Bipolar Disorder and Its Spectrum
Section 1:
Recognition and Diagnosis of Bipolar Disorder and Its Spectrum
The 2007 MEASUREme™ Resource Module discusses the challenges associated with recognizing and diagnosing bipolar disorder, as well as comorbid conditions that occur frequently and can complicate diagnosis. Pharmacologic treatment options (including a discussion of the use of antidepressants in bipolar disorder) and nonpharmacologic approaches to bipolar disorder will also be presented.
This first slide section focuses on the recognition and diagnosis of bipolar disorder and its spectrum.

2. Spectrum 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
Spectrum of Bipolar Disorders
Since 1921 when Emil Kraepelin described manic depression (bipolar disorder) as a psychiatric illness differentiated from schizophrenia, the definition of bipolar disorder has been expanding. We realize today that bipolar disorder is not a single, definable psychiatric illness, but rather a spectrum of disorders, which are listed on this slide.
Bipolar I—one or more manic episodes or mixed episodes and often one or more major depressive episodes
Bipolar II—one or more major depressive episodes accompanied by at least one hypomanic episode
Hypomania—elevated mood lasting at least 4 days
Cyclothymia—milder form of bipolar disorder
Bipolar NOS – not otherwise specified
Rapidly changing mood swings (ie, rapid cycler)
Major depression with family history of bipolar disorder
Antidepressant-induced mania/hypomania
Secondary mania (illness or drug-induced)
American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. 2nd ed. Washington, DC; 2002.
Adapted from American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. 2nd ed. Washington, DC; 2002.

3. Bipolar 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
Bipolar Terminology
Hypomania differs from mania. Many patients do not recognize they are in a hypomanic state. They describe this time as feeling good. Therefore, the professional must carefully question the patient about their psychiatric history and ask them to describe the “up” episodes in their life.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.

4. Bipolar 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
Bipolar Terminology (cont)
Other states of “mixedness” within the bipolar parameters are only now being focused on and studied. The bipolar continuum includes the mixed episode state where the patient is in a state of flux and demonstrating characteristics of both depression and mania.
Cyclothymia is a condition with alternating mood states that demonstrates a range from hypomania to mild depression.
Bipolar NOS is a fluctuating state that is ill-defined and never demonstrates a full mania or deep depressive episode.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.

5. 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
Bipolar Disorder NOS
Bipolar disorder not otherwise specified (NOS) refers to a mood episode that does not meet criteria for any specific bipolar disorder.
This slide summarizes several examples of bipolar disorder categorized as NOS based on DSM-IV criteria.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.

6. This cartoon illustrates the manic and depressive symptoms of bipolar disorder to look for in diagnostic interviews.

7. Diagnostic Criteria for Major Affective Disorders (DSM-IV)
Depressive Episode
Manic or Mixed Episode
Hypomanic Episodes
Bipolar I Disorder
Common but not required
≥ 1 required
Bipolar II Disorder
None allowed
Bipolar Disorder NOS*
Required, but do not meet criteria for a specific bipolar disorder
Cyclothymic Disorder
Dysthymia, but not major depression
Numerous periods over
2 years required
Major Depressive Disorder
Dysthymic Disorder
≥ 2 years required but not major depression
Diagnostic Criteria for Major Affective Disorders (DSM-IV)
This slide outlines the DSM-IV criteria for diagnosis of the various bipolar disorders based on the presence of depressive, manic, mixed, or hypomanic episodes.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000:
*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; 2000:

8. Diagnosing 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 20–40% risk of bipolar illness
Symptom overlap with other psychiatric conditions
Previous misdiagnosis common
Many clinically prominent psychiatric and medical comorbidities
Diagnosing Bipolar Disorder: Challenges
The diagnosis of bipolar disorder is not always straightforward, as confounding symptoms and other medical problems may lead the clinician to misdiagnose the illness. One reason is that patients with bipolar disorder often report symptoms of depression at the time of initial presentation.
Thomas P. The many forms of bipolar disorder: a modern look at an old illness. J Affect Disord. 2004;79(suppl 1):S3-S8.
Berk M, Berk L, Moss K, Dodd S, Malhi GS. Diagnosing bipolar disorder: how can we do it better? Med J Aust. 2006;184:
Thomas P. J Affect Disord. 2004;79(suppl 1):S3-S8.
Berk M, et al. Med J Aust. 2006;184:

9. The Bipolar Spectrum: Stronger
Bipolar I
 1 week
Bipolar II
 4 Days
Bipolar NOS
< 4 Days
The Bipolar Spectrum: Stronger
Support has grown in recent years for the concept of a broad bipolar spectrum, which evolved from Kraepelin’s description of a continuum between manic and depressive states.
This slide is adapted from Akiskal’s 1999 report in which intermediary subtypes of bipolar disorder, reflecting clinical observations, were delineated.
Clinical descriptions of these subtypes are as follows:
Bipolar I: Full Blown Mania – major depression alternates with full-blown manic episodes
Bipolar II: Depression with Hypomania – moderate to severe impairing motor depression, interspersed with periods of hypomania at least 4 days duration without impairment
Bipolar II ½: Cyclothymic Depressions – short hypomania with recurrent pattern of period of excitement, followed by minidepressions, with superimposed major depressive episode
Bipolar III: Antidepressant-Associated Hypomania – development of hypomanic or manic episodes during antidepressant treatment, mediated by cyclothymic temperamental tendencies, and differing from clinical depression
Bipolar III ½: Bipolar Masked and Unmasked by Stimulant Abuse – in bipolar type I and II patients with discrete episodes of excitement of manic/hypomanic intensity, in whom periods of excitement are so closely linked with substance abuse that it is not possible to determine whether they would have occurred in the absence of abuse
Adapted from Akiskal HS, Pinto O. The evolving bipolar spectrum. Prototypes I, II, II, and IV. Psychiatr Clin North Am. 1999;22:
“Bipolar III”
Antidepressant-related hypomania
Adapted from Akiskal HS, Pinto O. Psychiatr Clin North Am. 1999;22:

10. The Bipolar Spectrum: Weaker
Hyperthymic
“Bipolar IV”
Depressive Mixed State “IV ½”
Recurrent “Unipolar” Depression “Bipolar V”
The Bipolar Spectrum: Weaker
Bipolar IV: Hyperthymic Depression – refers to patients with clinical depression that occurs later in life and is superimposed on a lifelong hyperthymic temperament
Bipolar IV½ – refers to patients with clinical depression co-occurring with manic symptoms
Bipolar V: Recurrent Unipolar Depression – refers to depressed patients with a family history of bipolar illness; this subtype is not yet well-defined
Akiskal HS, Pinto O. The evolving bipolar spectrum. Prototypes I, II, III, and IV. Psychiatr Clin North Am. 1999;22:
Akiskal HS, Akiskal KK, Lancrenon S, et al. Validating the bipolar spectrum in the French National EPIDEP study: overview of the phenomenology and relative prevalence of its clinical prototypes. J Affect Disord. 2006;96:
Adapted from Akiskal HS, Pinto O. Psychiatr Clin North Am. 1999;22:
Akiskal HS, et al. J Affect Disord. 2006;96:

11. Bipolar “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
Bipolar “Missed States!” (Mixed States)
Berk et al, recently suggested that the definitions of bipolar mixed state form a spectrum extending from the existence of manic symptoms within depression to depressive symptoms within mania.
The two essential manifestations of bipolar disorder mixed state are manic dysphoria, which occurs more frequently in women and is characterized by irritable and dysphoric mood intruding into mania, and depressive mixed state, which involves the emergence of manic features, such as racing thoughts in a predominantly depressive presentation.
Suppes et al, recently found that mixed hypomania is common in patients with symptoms of hypomania, especially in women. The clinical importance of mixed hypomania, sometimes called dysphoric hypomania or hypomania with co-occurring depressive symptoms, is that patients with bipolar II disorder may be misdiagnosed with unipolar depression because of lack of recognition of hypomanic periods. This supports the need for careful assessment to identify depressive symptoms in patients with hypomania and to carefully assess for the presence of hypomania in patients with depressive symptoms.
Berk M, Berk L, Moss K, Dodd S, Malhi GS. Bipolar missed states: the diagnosis and clinical salience of bipolar mixed states. Aust N Z Psych. 2005;39:
Suppes T, Mintz J, McElroy S, et al. Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry. 2005;62:
Berk M, et al. Aust N Z Psych. 2005;39:
Suppes T, et al. Arch Gen Psychiatry. 2005;62:

12. Self-Rated Screening Tool: The 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
Self-Rated Screening Tool: The Mood Disorder Questionnaire (MDQ)
The Mood Disorder Questionnaire (MDQ) is a validated self-report instrument that screens for the presence of a lifetime history of bipolar disorder. The questionnaire includes 13 yes/no items derived from DSM-IV criteria and clinical experience. While the MDQ is an important screening tool, it should not replace a full diagnostic evaluation by a mental health care professional.
Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.
Hirschfeld RM, et al. J Clin Psychiatry. 2003;64:53-59.

13. Bipolar Disorder Diagnosis Is Often Missed
> 85,000 US adults surveyed
Positive screen rate for bipolar illness: 3.7% (> 6 million people in US)
For those with positive screen
Diagnosed with bipolar disorder
20%
Neither bipolar disorder nor depression diagnosis
49%
Bipolar Disorder Diagnosis is Often Missed
Bipolar disorder typically develops in late adolescence or early adulthood and affects both sexes equally. It frequently occurs within families, although genetic factors are only part of the cause.
The statistic most commonly cited is that more than 2 million US adults, or about 1% of the population, have bipolar disorder. However, in a community survey of more than 85,000 people in the US (2003: National Depressive and Manic-Depressive Association 2000 Survey of Individuals With Bipolar Disorder):
3.7% (almost 1 in 25 adults) screened positive for bipolar I or bipolar II disorder
This translates into more than 6 million US adults who could have the disorder
Only 20% of those who screened positive had been told by their doctors that they had bipolar disorder
Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.
Diagnosed with depression but 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. 2003;64:53-59.

14. Unipolar 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
Unipolar Misdiagnosis May Lead to Inappropriate Treatment
Bipolar disorder is a serious, recurrent, and sometimes chronic psychiatric illness that is far more prevalent than many physicians realize. It is often unrecognized and misdiagnosed, particularly in patients presenting with depression. Misdiagnosis of bipolar disorder as unipolar depression can lead to years of inappropriate treatment, which may in turn lead to mania, hypomania, or rapid cycling.
In one retrospective study that reviewed charts of 85 patients, more than one-third of patients were misdiagnosed as having unipolar depression.
Incredibly, of the 19 bipolar patients whose first or hypomanic episode occurred prior to their first visit to a mental health professional, 7 (37%) were nonetheless diagnosed with unipolar major depressive disorder.
Of 38 bipolar patients who received antidepressants as part of their initial treatment, 55% (21/38) developed mania or hypomania and 23% (8/35) developed new or accelerated rapid cycling while taking the antidepressant.
Treatment for bipolar disorder was delayed on average 8-10 years.
Although this is an uncontrolled, small sample, it suggests that misdiagnosis of bipolar disorder as unipolar depression is a serious problem, even when patients have already experienced a manic or hypomanic episode. Treatment with antidepressants may exacerbate or initiate rapid cycling in these patients.
Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61:
n = 35
Mania/ Hypomania
Rapid Cycling
Development of mania/hypomania or rapid cycling while taking antidepressants.
Ghaemi SN, et al. J Clin Psychiatry. 2000;61:

15. The 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
The Hazards of Misdiagnosis and Delayed Diagnosis in Bipolar Disorder
This slide lists some of the serious consequences that can result from the misdiagnosis or delayed diagnosis of bipolar disorder.

16. Self-Report Diagnostic Tools For Screening Bipolar Disorder
Scale
Description
Limitations
Mood Disorder Questionnaire (MDQ)
13 item questionnaire ( 7 is a positive screen)
More sensitive for bipolar I than II, should not replace a full diagnostic interview
Bipolar Spectrum Diagnostic Scale (BSDS)
Screens for subtle versions of bipolar and can rate the probability of bipolar as high, moderate, low, or unlikely
Should not replace a full diagnostic interview
Quick Inventory for Depression Symptomatology
(QIDS)
16 item inventory, each item rated 0-3
Takes an average of 15 minutes to implement
Self-Report Diagnostic Tools For Screening Bipolar Disorder
A number of scales are available to assess the potential for bipolar disorder and the current mood states of those with bipolar disorder. This slide summarizes the features and limitations of 3 self-report diagnostic tools used for screening bipolar disorder.

17. Clinician-Administered Diagnostic Tools For Screening Bipolar Disorder
Scale
Description
Limitations
Young Mania Rating Scale (YMRS)
11 item scale, each with a varied rating scale based on severity (mania = 12, depression = 3, euthymia = 2)
Usefulness of scale is limited in populations with diagnoses other than mania
Bipolarity Index
Evaluation of bipolar presentation based on 5 “dimensions”—each worth up to 20 points for a total of 100
Time consuming, not peer reviewed
Hamilton Rating Scale for Depression (HAM-D)
17-21 item scale initially intended for identifying depressed patients
Relies heavily on clinical interviewing skills and experience of the rater
Montgomery-Asberg Depression Rating Scale
(MADRS)
10 selected items are rated on a scale of 0-6 with anchors at 2-point intervals
Cost prohibitive and time consuming
Clinician-Administered Diagnostic Tools For Screening Bipolar Disorder
This slide summarizes the features and limitations of 4 clinician-rated diagnostic tools used for screening bipolar disorder.

18. Subthreshold 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
Subthreshold Bipolar Disorder (The “Soft” Bipolar Spectrum)
The boundaries of bipolar spectrum have expanded over the years, suggesting that the DSM-IV diagnostic criteria for hypomania need revision to include a broader concept based on hard and soft definitions of hypomania and bipolar disorder.
A proper definition of hypomania is crucial to diagnosing bipolar II disorder and subsyndromal bipolar disorder.
Hypomanic symptoms only, associated with major or mild depression, are important indicators of bipolarity.
A 20-year prospective community cohort study by Angst et al, suggests the existence of a wide and highly prevalent spectrum of bipolar disorders and hypomania in the general population: a broad definition of bipolar II disorder yielded a total prevalence of soft bipolar disorder of 24%. This study supports a broader concept of soft bipolarity.
Akiskal HS. The bipolar spectrum--the shaping of a new paradigm in psychiatry. Curr Psychiatry Rep. 2002;4:1-3.
Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rossler W. Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord. 2003;73:
Akiskal HS. Curr Psychiatry Rep. 2002;4:1-3.
Angst J, et al. J Affect Disord. 2003;73:

19. The 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
The Rule of 3 Hinting at Soft Bipolarity (NOS) in a Clinically Depressed Person
In a 2005 report, Akiskal suggested that triads of particular behaviors, such as 3 or more failed marriages, 3 or more first degree relatives with affective illness, etc, (among those listed in this slide) in the patient’s or the patient’s family’s biographical history are specific for bipolar II disorder and can be useful in differentiating between BP II and unipolar depression.
Akiskal HS. Searching for behavioral indicators of bipolar II in patients presenting with major depressive episodes: the "red sign," the "rule of three" and other biographic signs of temperamental extravagance, activation and hypomania. J Affect Disord. 2005;84:
Akiskal HS. J Affect Disord. 2005;84:

20. Importance 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
Importance of Interviewing the Patient and Their Family
Interviewing both the patient and their family is critical to accurate diagnosis of bipolar disorder. An NIMH study examined gender-related risks of bipolar I disorder as part of the Genetics Initiative. Among patients admitted with major depression who were screened for bipolar disorder, twice as many bipolar I diagnoses were made when both the patient and family were interviewed.
Blehar MC, DePaulo JR Jr, Gershon ES, Reich T, Simpson SG, Nurnberger JI Jr. Women with bipolar disorder: findings from the NIMH Genetics Initiative sample. Psychopharmacol Bull. 1998;34:
Blehar MC, et al. Psychopharmacol Bull. 1998;34:

21. Physicians 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 he’s being heard; physician must try to understand how the world looks through patient’s 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
Physicians Must Use Patient Perspectives to Improve Diagnosis and Care
A panel of physicians recently categorized the unmet needs of patients with bipolar disorder and compared them with those cited by physicians. Among the factors necessary for recovery cited by patients were:
Better medications that are quick-acting and have fewer side effects
Treatment must be based on the provider’s judgment and not limited by restricted formularies
Effective patient-physician communication is essential; patient wants to feel the physician is listening and taking him seriously; physician must also ask patient more direct, targeted questions about all symptoms and family history
Patients want to feel they are jointly making treatment decisions with physicians as equal partners in their wellness plan
Lewis L, Hoofnagle L. Patient perspectives on provider competence: a view from the Depression and Bipolar Support Alliance. Adm Policy Ment Health. 2005;32:
Lewis L, et al. Adm Policy Ment Health. 2005;32:

22. Take 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
Take Home Messages
The diagnosis of bipolar disorder is clinically challenging and not always straightforward.
Bipolar disorder is not a single, definable psychiatric illness, but rather a spectrum of disorders, often masquerading as mixed states, and it is often misdiagnosed.
Misdiagnosis of bipolar disorder as unipolar depression can lead to years of inappropriate treatment, which may in turn lead to mania, hypomania, or rapid cycling. Other potentially serious consequences of misdiagnosis include increased suicide attempts or completion, violent, impulsive or indiscrete behavior, and worsening substance abuse.