Finally, some misdiagnosis likely arises from the lag between episodes. Patients may experience more subtle mood elevation (ie, hypomania) between or overlapping with depressive episodes. In some cases, patients may experience depressive episodes without a manic episode for 5 years or more thereafter—for the first few years of their illness, they are therefore "misdiagnosed" with recurrent major depressive disorder.14,15
Improving Diagnosis of Bipolar Disorder
In many cases, careful history-taking allows recognition of bipolar disorder. Two aspects are particularly important: the use of collateral informants, such as friends or family members wherever possible, and systematic inquiry about symptoms of depression, hypomania, and mania. For hypomania, some clinicians begin by looking for any period of abnormally elevated or irritable mood or change in behaviors, such as driving, spending, or sexual activity. These are all quite nonspecific, but if any such period can be defined, additional questions can focus on typical associated symptoms.
Although several diagnostic instruments exist, none can replace careful diagnostic evaluation.16 A helpful tool in the diagnostic process can be a patient-rated instrument, such as the Mood Disorder Questionnaire.17-19 This set of questions includes typical symptoms of mania and hypomania based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSMIV) criteria; a typical question asks whether there has ever been a period of time when "you were much more social or outgoing than usual, for example, you telephoned friends in the middle of the night?" Obviously, although not sufficient to diagnose bipolar disorder in and of itself, this instrument can lay the groundwork for more detailed follow-up questions to clarify diagnosis.
Although the diagnostic criteria for mania have been demonstrated to have high interrater reliability—ie, 2 clinicians faced with a manic patient applying DSM-IV criteria would be likely to arrive at the same diagnosis—those for hypomania show somewhat less reliability.20 Apart from the use of structured interviews or questionnaires, perhaps the best opportunity to improve diagnosis is through careful follow-up. Over time, hypomania or mood cycling may become more apparent, and the possible deleterious effects of antidepressants may be detected. Some form of mood charting16 by patients can also help where initial diagnosis is unclear.
The phase of illness that presents the most difficulty in diagnosis is typically depression: patients present in a depressive episode, and the clinician must assess the likelihood of bipolar disorder versus major depressive disorder. Unfortunately, although many studies have tried to identify clinical features of bipolar depression that distinguish it from major depressive disorder, none are particularly specific. For example, a number of studies describe reverse neurovegetative symptoms (increased sleep and appetite, rather than insomnia and loss of appetite) as being more common in bipolar depression.1-9 Irritability10,11 and anger12,13 may also be suggestive of bipolar disorder. However, it is important to emphasize that all of these symptoms are quite prevalent among patients with major depressive disorder as well.
Similarly, certain features of illness course have been suggested to indicate bipolarity. Bipolar disorder typically has earlier age at onset than major depression.14 Indeed, when it presents in childhood or adolescence it may be particularly difficult to identify, because mood episodes may be less distinct (with persistent mood lability or irritability more common), or symptoms may be attributed to attention-deficit/hyperactivity disorder. Bipolar disorder is also highly familial: having a first-degree relative with bipolar disorder certainly increases a patient's likelihood of having bipolar disorder by approximately 7-fold. On the other hand, bipolar patients frequently have unipolar family members and vice versa.15,16 Finally, highly recurrent depression, a history of abrupt antidepressant response followed by impersistence of response, or a history of numerous failed antidepressant trials, has been suggested to indicate bipolarity, although the evidence supporting this assumption is limited.
In sum, none of these individual clinical features are diagnostic for bipolarity. Rather, their presence should increase the clinician's suspicion of bipolar disorder and lead to even greater scrutiny (both in terms of past history and future course) for manic and hypomanic symptoms.
Consequences of Overdiagnosis
Of course, any diagnostic tool for bipolar disorder represents a tradeoff between sensitivity and specificity. Decreasing the rate of underdiagnosis generally entails some increase in the rate of false-positives—in this case, patients with major depressive disorder treated for bipolar disorder. Risks include exposure to a greater medication burden (in some cases requiring additional monitoring) as well as lesser likelihood of clinical improvement. Unfortunately, the tolerability of most bipolar pharmacotherapies is relatively poor compared with antidepressants, with possible medical consequences including diabetes and weight gain.21 Moreover, the evidence in controlled trials that bipolar pharmacotherapies, such as atypical antipsychotics or valproate, are effective antidepressants for individuals with major depressive disorder is generally lacking, with the possible exception of lithium.22-24 Having committed a patient to mood stabilizer treatment, clinicians are often loathe to reverse themselves, so a misdiagnosis is likely to persist. However, as with any other diagnosis in psychiatry, periodic reconsideration of both diagnosis and treatment regimen is warranted.
The accurate discrimination of bipolar disorder from major depressive disorder, with which it is most often confused, is receiving increasing attention as its clinical and economic consequences are recognized. Ultimately, the use of biological markers—brain imaging or genetic tests, for example—may facilitate early and accurate diagnosis. While such markers are developed, careful clinical evaluation remains the most useful tool for recognizing bipolar disorder.
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