Strategies for the Early Recognition of Bipolar Disorder
Terence A. Ketter, MD
Department of Psychiatry and Behavioral Sciences, and the Bipolar Disorders Clinic, Stanford University School of Medicine, Stanford, California
Missed Diagnoses and Misdiagnoses of Bipolar Disorder
Two challenges to the early recognition of bipolar disorder are missed diagnoses and misdiagnoses. Missed diagnoses are particularly common in childhood and adolescence, often due to age-dependent presentations or comorbid conditions that capture the clinician’s attention. Missed diagnoses can also occur because some children never see a mental health care provider or a primary care physician who is attuned to early bipolar disorder presentations.
Misdiagnosis occurs when a patient receives a diagnosis for a disorder other than the one he or she actually has. A survey1 conducted in 2000 found that 69% of patients with bipolar disorder first received a diagnosis other than bipolar disorder (AV 1). Among those misdiagnosed, over half received a diagnosis of MDD.1 For patients with bipolar disorder who are initially misdiagnosed, a 9- to 10-year latency from first symptom onset to a correct bipolar diagnosis and appropriate treatment has been reported.1–3
Prevalence and features of early onset. The first bipolar episode occurs before adulthood in approximately two-thirds of patients.1,4 Rates of missed diagnoses and misdiagnoses could be reduced through increased alertness of the prevalence of bipolar disorder in younger populations. Improving diagnosis of bipolar disorder in children and adolescents may improve patient outcomes, as early onset of bipolar disorder is associated with increased treatment delay and worse illness course (eg, more episodes, more comorbidities, and greater severity) compared with onset during adulthood5; however, this relationship may or may not be causal.4
Identifying characteristics of bipolar disorder that are specific to children and adolescents may contribute to a reduction in missed diagnoses and misdiagnoses in this population (AV 2). For example, rapid cycling is more common in youths than in adults, occurring in over 85% of young patients.6 Mixed mania and grandiose delusions are each seen in about half of young patients. Suicidality occurs in one-fourth of young patients.
In recent years, increased attention to the possibility of bipolar disorder in children and adolescents may have contributed to a diagnostic problem in the opposite direction—that is, overdiagnosing bipolar disorder in young patients with problems such as temper tantrums. Carefully assessing children and adolescents for bipolar disorder using the DSM criteria as well as looking for the presence or absence of a family history of bipolar disorder can help avoid overdiagnosis.
Comorbidity. Early onset of bipolar disorder is associated with Axis I comorbidity, and over 60% of adults with bipolar disorder have a lifetime comorbid Axis I disorder.7 Anxiety disorders, substance use disorders, and mood disorders coaggregate, so finding 1 of these 3 disorders should always lead to screening for the other 2 disorders.
In childhood and adolescence, ADHD is one of the most common conditions comorbid with bipolar disorder. ADHD occurs in up to 90% of child and adolescent cases of bipolar disorder.6 Researchers8 have identified differences between the 2 conditions that, combined with characteristics described in the DSM-IV-TR,9 can help clinicians distinguish between them (AV 3). Carefully distinguish bipolar disorder from ADHD; keeping in mind that they can co-occur may facilitate a more accurate diagnosis.
Detecting Prior Manic, Hypomanic, and Mixed Episodes
One reason that misdiagnoses of MDD are so common in patients with bipolar disorder is that manic symptoms are often missed for several reasons: depressive episodes are often the first episodes in patients with bipolar disorder, bipolar symptoms are predominantly depressive, and depressive symptoms are commonly chief complaints when patients present for assessment and treatment.10,11 The detection of prior mania or hypomania in currently depressed patients can be challenging, which complicates the differential diagnosis of bipolar disorder.
Mixed episodes, also called mixed mania, may be even more difficult to detect than manic or hypomanic ones. The DSM-IV-TR9 requires syndromal mania and syndromal depression for the diagnosis of mixed mania. The DSM does allow for concurrent diagnoses of hypomania and syndromal depression but does not give this mood state a specific name (such as the non-DSM term mixed hypomania), which can lead these episodes being misconstrued as agitated depression rather than mixed mania or mixed hypomania. Other non-DSM mixed episode-like definitions include syndromal mania or hypomania with subsyndromal depression (called dysphoric mania or dysphoric hypomania)12 or subsyndromal mood elevation with syndromal depression (called mixed depression).13 Thinking in terms of these definitions for types of episodes may make bipolar disorder easier to identify.
Clinicians must remember that mood elevation can be caused by alcohol and substance use and some medical conditions.11 Patients presenting with episodes of mood elevation should be screened carefully to differentiate primary (bipolar) mood elevation from mood elevation secondary to alcohol or substance use or medical conditions.
The MDQ is a simple, self-reported screening instrument for bipolar disorder. The adult version14 indicates the presence of bipolar disorder if an individual meets the threshold of at least 7 of 13 mood elevation criteria, while the adolescent version15 indicates possible bipolar disorder when at least 5 of 13 criteria for mood elevation are present. Both MDQ versions require that symptoms of mood elevation occur simultaneously and produce at least moderate negative consequences.
Hirschfeld et al16 used the MDQ to screen over 85,000 individuals. Of the over 3,000 individuals screening positive for bipolar disorder, approximately 31% had received a previous diagnosis of unipolar depression, 49% had received no diagnosis, and only about 20% had been diagnosed with bipolar disorder. The results of this study highlight the problem of missed diagnoses and misdiagnoses in bipolar disorder, but they also suggest that screening patients—especially those presenting with depressive symptoms—with the MDQ could help facilitate correct diagnoses in this population.
Patients presenting during a depressive episode often have poor recall of prior episodes of mood elevation, particularly if the prior mood elevation was hypomania rather than mania. Therefore, having patients’ significant others rate the patient with the MDQ can also provide very valuable collateral information, thereby increasing the sensitivity of the measurement tool.
Detecting Depression at Risk for Bipolar Outcome
As mentioned, bipolar disorder presenting with a depressive episode often leads to the misdiagnosis of unipolar MDD when prior manic or hypomanic symptoms are missed. Individuals with onset of a first major depressive episode during childhood, adolescence, or early adulthood are at risk for the development of bipolar disorder, since depression may be the initial mood episode in many patients with bipolar disorder (particularly female patients).17,18 Depression in prepubertal children and severe depression (particularly psychotic depression) in young adults were predictive of subsequent bipolar disorder in more than 40% of patients (AV 4).19,20
A family history of bipolar disorder is also very suggestive of the disorder.21,22 If an individual presenting with a depressive episode has a family history of bipolar disorder, the patient’s risk for having a bipolar outcome is at least double that of someone with no family history of bipolar disorder.23
Thus, risk factors for bipolar disorder include major depressive episodes with onset before 25 years of age, a history of psychosis, and having a first-degree relative with mania.17,23 Among patients with major depressive episodes, having 1 of these 3 characteristics yields an approximate 20% risk of also having mania, having 2 increases the risk to about 50%, and having all 3 further increases the risk to about 67%.23 So, clinicians should screen for these risk factors and pay close attention to indications of mania when these risk factors are present in patients presenting with depression.
Antidepressant monotherapy and, in some instances, even an antidepressant combined with an antimanic agent can be problematic for patients with bipolar disorder, as such interventions may fail to relieve depression and may even promote rapid cycling or manic episodes in some patients. With this in mind, a history of problematic responses to antidepressant medications during depressive episodes may also suggest the possible presence of bipolar disorder rather than unipolar MDD.17
Mitchell et al24 published a list of characteristics associated with bipolar depression compared with characteristics more often associated with unipolar depression (AV 5). A careful assessment of the presence or absence of the listed illness characteristics can help physicians determine the risk that a patient presenting with depression might be experiencing a bipolar depressive episode.
Substantial diagnostic challenges make early detection of bipolar disorder difficult, but several strategies can be used to improve detection. Avoid misdiagnoses of patients presenting with depressive symptoms by assessing for a history of mood elevation symptoms, involving patients’ family members and significant others in the diagnostic process. Patients are perhaps more sensitive raters of their own depressive symptoms, whereas significant others may be more sensitive raters of mood elevation symptoms. Investigate patients’ family histories for bipolar disorder when possible. Use the current DSM criteria effectively and ask the patient directly if he or she has ever been diagnosed with bipolar disorder or mania or hypomania. Administer a bipolar disorder screening instrument such as the MDQ when patients present with depressive symptoms, particularly if they have never been treated with an antidepressant. Pay attention to age-dependent comorbidities that are associated with the presence of bipolar disorder, such as ADHD in younger patients and anxiety and substance use disorders in older patients, with the latter 2 also being common in patients with unipolar MDD. Look for characteristics that suggest possible bipolar versus unipolar outcomes in patients presenting with depression. Following these steps can increase the early diagnosis of bipolar disorder, which, in the long run, can yield more effective and timely treatment and better patient outcomes.
For Clinical Use
- Screen for a history of mania or hypomania in all patients with depressive symptoms
- Involve patients’ families or significant others in the diagnostic process
- Be aware of the risk factors and age-dependent presentations for bipolar disorder
ADHD = attention-deficit/hyperactivity disorder
DSM-IV-TR = The Diagnostic and Statistical Manual of Mental Health, Fourth Edition, Text Revision
MDD = major depressive disorder
MDQ = Mood Disorder Questionnaire
Take the online posttest.
- Hirschfeld RM, 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(2):161–174.
- Baethge C, Tondo L, Bratti IM, et al. Prophylaxis latency and outcome in bipolar disorders. Can J Psychiatry. 2003;48(7):449–457.
- Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61(10):804–808.
- Perlis RH, Miyahara S, Marangell LB, et al, for the STEP-BD Investigators. Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Biol Psychiatry. 2004;55(9):875–881.
- Leverich GS, Post RM, Keck PE Jr, et al. The poor prognosis of childhood-onset bipolar disorder. J Pediatr. 2007;150(5):485–490.
- Geller B, Zimerman B, Williams M, et al. Diagnostic characteristics of 93 cases of a prepubertal and early adolescent bipolar disorder phenotype by gender, puberty and comorbid attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 2000;10(3):157–164.
- McElroy SL, Altshuler LL, Suppes T, et al. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry. 2001;158(3):420–426.
- Geller B, Williams M, Zimerman B, et al. Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affect Disord. 1998;51(2):81–91.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
- Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530–537.
- Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60(3):261–269.
- McElroy SL, Keck PE Jr, Pope HG Jr, et al. Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry. 1992;149(12):1633–1644.
- Benazzi F, Akiskal HS. Psychometric delineation of the most discriminant symptoms of depressive mixed states. Psychiatry Res. 2006;141(1):81–88.
- Hirschfeld RMA, Williams JBW, Spitzer RL. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873–1875.
- Wagner KD, Hirschfeld RM, Emslie GJ, et al. Validation of the Mood Disorder Questionnaire for bipolar disorders in adolescents. J Clin Psychiatry. 2006;67(5):827–830.
- Hirschfeld RM, Vornik LA. Recognition and diagnosis of bipolar disorder. J Clin Psychiatry. 2004;65(suppl 15):5–9.
- Akiskal HS, Walker P, Puzantian VR, et al. Bipolar outcome in the course of depressive illness: phenomenologic, familial, and pharmacologic predictors. J Affect Disord. 1983;5(2):115–128.
- Perlis RH, Delbello MP, Miyahara S, et al. Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I Systematic Treatment Enhancement Program for Bipolar Disorder participants. Biol Psychiatry. 2005;58(7):549–553.
- Geller B, Zimerman B, Williams M, et al. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry. 2001;158(1):125–127.
- Goldberg JF, Harrow M, Whiteside JE. Risk for bipolar illness in patients initially hospitalized for unipolar depression. Am J Psychiatry. 2001;158(8):1265–1270.
- Gershon ES, Hamovit J, Guroff J, et al. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry. 1982;39(10):1157–1167.
- Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2007;64(9):1039]. Arch Gen Psychiatry. 2007;64(5):543–552.
- Othmer E, Desouza CM, Penick EC, et al. Indicators of mania in depressed outpatients: a retrospective analysis of data from the Kansas 1500 study. J Clin Psychiatry. 2007;68(1):47–51.
- Mitchell PB, Goodwin GM, Johnson GF, et al. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008;10(1, pt 2):144–152.