Screening for Bipolar Disorder

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Bipolar disorder is a recurrent and sometimes chronic illness involving episodes of depression and mania or hypomania. The most frequent presentation is depression: more than 1 of 5 primary care patients with depression have bipolar disorder. The symptoms of bipolar depression often differ from those of unipolar depression. Age of onset for bipolar disorder is usually the late teens; slightly older for bipolar II subtype. Nearly all patients with bipolar disorder suffer from a comorbid psychiatric disorder, most frequently an anxiety disorder. Although the most dramatic presentation of bipolar disorder is the acutely manic patient who presents to the emergency department, this presentation is much less frequently encountered in physicians’ offices, both primary care and psychiatric. Bipolarity is often missed in these situations. About half of bipolar patients have consulted 3 or more professionals before receiving a correct diagnosis, and the average time to first treatment is 10 years. It is imperative that clinicians carefully assess patients for bipolar disorder, especially those presenting with depression. In addition to patient and family history, administration of a screening instrument can be very helpful. The most widely used screening tool is the Mood Disorder Questionnaire. This screening tool will be discussed in this article regarding its use in outpatient clinics and the community.

(Am J Manag Care. 2007;13:S164-S169)

What Is Bipolar Disorder?Bipolar disorder is a serious recurrent and sometimes long-term psychiatric disease, characterized by mood dysregulation and corresponding impulsivity, risk-taking behavior (eg, alcohol abuse, sexual indiscretion, excessive spending), and interpersonal difficulties.1 Individuals with bipolar disorder are at increased risk for death from suicide, physical illness (eg, cardiovascular disease), homicide, and accidents.1 Recent data suggest that, of prevalent neuropsychiatric disorders, bipolar disorder ranks second only to depression in the loss of healthy life-years because of premature death or disability.2

Research on bipolar disorder has mainly focused on bipolar I disorder. A diagnosis of bipolar I requires at least 1 episode of mania, defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) as a week or longer period of abnormally elevated or irritable mood with associated symptoms, such as decreased need for sleep, more talkative than usual, racing thoughts, and excessive involvement in high-risk activities.3 A manic episode causes a marked impairment in social or occupational functioning and often requires hospitalization.

Bipolar II disorder requires a history of at least 1 major depressive episode, at least 1 hypomanic episode, and no history of mania.3 Hypomania is characterized by a distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, which is clearly different from the patient's usual nondepressed mood.3 However, many clinicians believe that the “4-day rule†specified on the DSM-IVTR criteria for hypomania is too restrictive because it does not capture those patients with bipolar II disorder who have hypomanic periods lasting 1 to 3 days.4

Typical features of hypomania include inflated self-esteem/ grandiosity; decreased need for sleep; increased talkativeness; “flight of ideas†or racing thoughts; distractibility; increased psychomotor activity; and increased impulsivity, such as buying sprees or inappropriate sexual activity. In contrast to mania, hypomania usually does not result in severe social or vocational impairment, or in hospitalization. Clearly, these outcomes may vary, depending on the patient and his or her clinicians. Furthermore, in contrast to mania, psychotic features are not present in hypomania, although there can be psychotic features during depression. It is important to point out that hypomania may not be euphoric. Often it presents with irritability.

Patients with bipolar II disorder generally present with major depressive symptoms, including a sad or empty feeling, hopelessness, apathy, undue worry, or irritability. Suicidal ideation or plans may also be present. The hypomania of bipolar II disorder may first manifest itself after antidepressant treatment. However, hypomania is not diagnosed when the patient's symptoms are the direct physiologic effects of a general medical condition (eg, hyperthyroidism) or a drug (eg, amphetamine or cocaine abuse).3

Cyclothymic disorder is characterized by at least 2 years of numerous periods of hypomanic symptoms and numerous periods of depressive symptoms that do not meet criteria for a major depressive episode.3 Table 1 summarizes the essential features of these bipolar subtypes.

The symptoms of bipolar depression often differ from those of unipolar depression. Bipolar depression often involves increased sleep, hyperphagia, weight gain, and psychomotor slowing. A history of psychotic features while depressed may also be more common in bipolar (vs unipolar) major depression.4,5

The most recent data on bipolar disorder yield a lifetime community prevalence of 1.0% for bipolar I disorder, 1.1% for bipolar II disorder, and 2.4% for subthreshold bipolar disorder, totaling 4.4% for this spectrum of bipolar disorder.6 Age of onset is usually the late teens for bipolar I and slightly older for bipolar II. Nearly all patients with bipolar disorder suffer from another psychiatric disorder. The most frequent comorbid disorders are anxiety disorders, seen in nearly three quarters of patients with bipolar disorder. Next are impulse control disorders, and finally substance use disorders, including about 4 of 10 patients with bipolar disorder.6

Identification of Bipolar Disorder in Clinical PopulationsPerhaps the most dramatic presentation of bipolar disorder is the acutely manic patient who may have delusions of being able to fly, is bursting with energy, is aggressive, and whose behavior is wildly inappropriate. Manic episodes are frequently medical emergencies and such patients are often brought to the emergency department by the police or by ambulance and subsequently hospitalized. This presentation, however, is much less frequent than those seen in physicians' offices, both primary care and psychiatric. Unfortunately, bipolarity is often missed in these situations, because manic or hypomanic symptoms may be more subtle or not appreciated as such in a patient's recollection of past history. Importance of Correct Diagnosis This lack of recognition of and attention to bipolar disorder leads to substantial delay in patients' receiving an accurate diagnosis. In a survey of its members completed in the early 1990s, the National Depressive and Manic-Depressive Association (DMDA), a patient self-help and advocacy group, found that nearly one quarter of patients consulted a professional within 6 months of symptom onset.7 However, 48% consulted 3 or more professionals before receiving a correct diagnosis, and 10% consulted 7 or more professionals. Thirty-four percent waited 10 years or more for their first diagnosis of bipolar disorder.7 In another sample of bipolar patients entering the Stanley Foundation Bipolar Treatment Outcome Network, the average length of time for first treatment of bipolar disorder was 10 years.8 In a repeat of the national DMDA survey about a decade later, the results were very similar: 35% of DMDA members reported waiting 10 years or more for their first accurate diagnosis of bipolar disorder.9

This delay in diagnosis often has substantial adverse results. Patients do not get the appropriate treatment to alleviate their symptoms. They may even get treatments that exacerbate their symptoms, such as antidepressants that precipitate mania and produce rapid cycling. Mistreatment of bipolar disorder as unipolar depression can trigger manic episodes or otherwise destabilize the illness. In a study of patients with bipolar disorder who previously had been mistreated for unipolar depression, 55% developed mania or hypomania, and 23% developed new or accelerated rapid cycling.10

The presentation for bipolar disorder in physicians' offices varies greatly (Table 2). The patient may complain of insomnia, irritability, low energy, difficulty focusing, and difficulty with relationships. A very common presentation involves problems controlling drinking or drug abuse. The most frequent presentation is depression. In primary care settings, more than 1 of 5 patients with depression in fact have bipolar disorder. For example, in a recent study of patients being treated with antidepressants in a family medicine clinic in Galveston, 21% screened positive for bipolar disorder.11 Two thirds of these patients had been undiagnosed for bipolar disorder. In a study of 108 consecutive outpatients diagnosed with depression and anxiety in a private family practice setting, 26% had bipolar disorder, most of whom had bipolar II disorder.12 In a study of depressed patients in an urban general medicine clinic serving a lowincome population, more than 23% of patients with current major depression screened positive for bipolar disorder.13

Rates of bipolar disorder in depressed patients seen by psychiatrists are even higher. In a sample of 203 patients with major depression in a private practice setting in Italy, 49% had bipolar disorder, most of whom were bipolar II.14 In a sample of patients with major depressive episodes in France, 28% had bipolar disorder.15 A careful reappraisal with a research interview found even higher rates in this same sample.

These data strongly support the high frequency of bipolar disorder in patients with depression, predominantly the bipolar II subtype. Unfortunately, most of these patients do not receive an accurate and correct diagnosis of bipolar disorder. This can lead to inappropriate treatment, which may well make the illness worse. Therefore, it is imperative that clinicians carefully assess patients for bipolar disorder, especially those presenting with depression.

How to Identify Patients With Bipolar DisorderPatients with bipolar disorder, especially those who are currently depressed, present to mental health professionals and to primary care providers with a variety of clinical pictures. Therefore, diagnosis of the illness may easily be missed. Recognition may be improved substantially by looking for bipolar disorder and by asking a few well-directed questions.

In patients with depression, it is very important for the clinician to ask whether there has been a history of mania or hypomania (Table 3). It is also useful to ask patients whether they have had mood swings or episodes of being “high†that are characterized by increased energy, decreased need for sleep, and altered mood. It is informative to ask about family history of bipolar disorder. Although patients may not know if a relative had bipolar disorder, they may have heard the phrase “manic depressive illness†or knew a relative who had been admitted to a psychiatric hospital. A history of suicide or substance abuse is also suggestive of bipolar illness.

It is helpful to include family members or significant others in the evaluation process because patients with bipolar disorder often lack insight, especially memory of “high†periods. Reports from such collateral sources can be invaluable.

Finally, administration of a screening instrument can be very helpful in identifying patients likely to have bipolar disorder. The most widely used screening instrument for bipolar disorder is the Mood Disorder Questionnaire (MDQ).16

The Mood Disorder QuestionnaireThe MDQ is a self-report, single-page, paper-and-pencil inventory that can be quickly and easily scored by a physician, nurse, or any trained medical staff assistant. The MDQ screens for a lifetime history of a manic or hypomanic syndrome by asking 13 yes-or-no items derived from the DSM-IV criteria and from clinical experience (Table 4).16 An additional question asks whether several of any reported manic or hypomanic symptoms or behaviors were experienced concurrently. Finally, the level of functional impairment resulting from these symptoms is also assessed.

A positive screen for bipolar disorder includes answering at least 7 of the yes-or-no questions positively, scoring “moderate†or “serious†for impairment, and “yes†for co-occurrence of symptoms. The MDQ has been used in several studies and has proved to be an excellent tool in identifying patients likely to have bipolar disorder.11,17-23

The MDQ in the Clinic

The MDQ was tested as a screen for bipolar disorder in the general community and sent to 100 000 demographically representative US households.23 A supplemental mailing was sent to 27 800 individuals who were selected to improve the representative nature of the combined samples for matching adults aged 18 years or older. Almost 72% (71 836) of the questionnaires were returned within 6 weeks, and 64.7% (17 973) of the individual-based questionnaires were returned within 5 weeks. The final data set analyzed included 85 358 (66.8%) usable returns. The prevalence of bipolar disorder as measured by the MDQ was 3.7%.23

Screening for Bipolar Disorder in Adolescents A version of the MDQ has recently been developed to improve identification of bipolar disorder in adolescents (Table 5).24 The MDQ-Adolescent Version (MDQ-A) screens for bipolar disorder in adolescents (ages, 12-17 years).24 The MDQ-A has the same 13 yes-or-no questions and queries about psychosocial impairment (eg, school, social, legal problems) and co-occurrence. The difference is that it is filled out by the parent, not the adolescent. Involving a parent has yielded excellent results–a sensitivity of 72% and a specificity of 81%. The utility of the instrument dropped sharply when it was filled out by adolescents themselves, which perhaps reflects the lack of insight so characteristic of the illness.

A positive screening does not signify that the patient in fact has bipolar disorder. A thorough examination, assessing general medical condition, comprehensive psychiatric evaluation, and use of medications and other substances, is necessary.

Conclusion

Address correspondence to: Robert M. A. Hirschfeld, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, 1.302 Rebecca Sealy, 301 University Blvd, Galveston, TX 77555-0188. E-mail: rohirsch@utmb.edu.

Disclosure: Dr Hirschfeld serves as a consultant to or is on the advisory board of the following: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Organon, Inc, Pfizer, Inc, Shire, UCB Pharma, and Wyeth-Ayerst.1. Hirschfeld RMA, Vornik LA. Recognition and diagnosis of bipolar disorder. J Clin Psychiatry. 2004;65(suppl 15):5-9.

3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.Washington, DC: APA; 2000:382-401.

5. Mitchell PB, Wilhelm K, Parker G, Austin MP, Rutgers P, Malhi GS. The clinical features of bipolar depression: a comparison with matched major depressive disorder patients. J Clin Psychiatry. 2001;62:212-216.

7. Lish JD, Dime-Meenan S, Whybrow PC, Price RA, Hirschfeld RMA.The National Depressive and Manic-Depressive Association (DMDA) survey of bipolar members. J Affect Disord. 1994;31:281-294.

9. Hirschfeld RMA, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic- Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64:161-174.

11. Hirschfeld RMA, Cass AR, Holt DC, Carlson CA. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Pract. 2005;18:233-239.

13. Olfson M, Das AK, Gameroff MJ, et al. Bipolar depression in a low-income primary care clinic. Am J Psychiatry. 2005;162:2146-2151.

15. Hantouche EG, Akiskal HS, Lancrenon S, et al. Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord. 1998;50:163-173.

17. Hirschfeld RMA, Holzer C, Calabrese JR, et al. Validity of the Mood Disorder Questionnaire: a general population study. Am J Psychiatry. 2003;160:178-180.

19. Mangelli L, Benazzi F, Fava GA. Assessing the community prevalence of bipolar spectrum symptoms by the Mood Disorder Questionnaire. Psychother Psychosom. 2005;74:120-122.

21. Miller CJ, Klugman J, Berv DA, Rosenquist KJ, Ghaemi SN. Sensitivity and specificity of the Mood Disorder Questionnaire for detecting bipolar disorder. J Affect Disord. 2004;81:167-171.

23. Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.