The depressive phases of bipolar disorder predominate the disease's course, in initial episodes, as well as in relapse. Therefore, it is challenging to make an early and accurate diagnosis of the disorder. Early recognition and management of bipolar disorder may arrest the long-term progressive tendency of the illness. This arrested progression, in turn, can prevent the emergence of substance abuse problems, rapid cycling, and resistance to pharmacologic treatment, as well as negative consequences associated with social and occupational dysfunction.
Although early diagnosis of bipolar disorder can be difficult for even the most experienced physicians, there are diagnostic clues that primary care physicians can incorporate into their clinical assessments to raise sensitivity to the disorder. The first, and most important, step is to consider bipolar disorder within the differential diagnosis when assessing a patient with complaints of mood change (
Figure 1). As physicians remember that unipolar depression is a diagnosis of exclusion, their recognition of bipolar depression, as well as mood disorders secondary to medical conditions and substance use disorders, will improve.
9
During patient evaluations, physicians should consider clinical features suggestive of bipolar depression, the most important of which make up the points of what may be referred to as the
bipolar diagnostic star (
Figure 2).
10,11 Among these features is
early age of onset, as evidence suggests that most patients with bipolar disorder have onset of illness before 20 years of age.
12 (Patients with unipolar disorder tend to have a later average age of onset.) The earlier the onset of mood symptoms, the greater the likelihood of a diagnosis of bipolar disorder versus unipolar disorder. Another consideration is
family history of mental illness, and, more specifically, family history of bipolar disorder. The disease appears to be an autosomal-dominant disorder with incomplete penetrance, and a 70% concordance rate in monozygotic twins.
13
Physicians should note the presenting symptoms, as well as the course of the symptoms. They should screen all patients with depression for manic and hypomanic symptoms, and question patients' history of episodes. Symptoms of mania can co-occur with depressive symptoms, a phase of bipolar disorder known as “mixed state.” Unfortunately, bipolar disorder, mixed state is frequently misdiagnosed as agitated depression. Physicians should consider the diagnosis of bipolar disorder, mixed state when a patient has predominating symptoms of agitation, irritability, anxiety, and insomnia that occur against a background of depressive symptoms.
Other presenting or classic symptoms suggestive of bipolar disorder include hypersomnia, psychomotor retardation, abrupt onset, termination of episodes (eg, “mood swings,” postpartum episodes of depression), and the presence of comorbidities (eg, substance abuse, anxiety disorders, attention-deficit hyperactivity disorder [ADHD]).
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The final consideration is patients'
prior response to treatment. The antidepressant refractory depression rate is reported to be as high as between 30% and 40%.
14 Part of the explanation for this astonishing treatment failure rate can be attributed to a lack of diagnostic precision. Antidepressant failure or adverse reactions while patients are on antidepressant therapy can be important clues leading to a diagnosis of bipolar disorder, as patients with bipolar disorder generally do poorly on antidepressant monotherapy. In fact, tricyclic antidepressant agents have long been associated with induction of mania, hypomania, and cycle acceleration when used alone as treatment.
15
It appears from other data, however, that selective serotonin reuptake inhibitors (SSRIs) and bupropion hydrochloride impart much less risk.
16 Nonetheless, antidepressant monotherapy, regardless of the agent chosen, is contraindicated in patients with bipolar depression. The use of a safer antidepressant (eg, SSRIs, bupropion hydrochloride) in combination with a mood stabilizer, however, can be highly effective. This efficacy is evidenced by the recent US Food and Drug Administration (FDA) approval of the olanzapine-fluoxetine hydrochloride combination for the treatment of patients with acute bipolar depression.
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In addition to the five points of the bipolar disorder diagnostic star, physicians should consider other features in the evaluation of patients with depression. Given the seriousness of the symptomatology, as well as the high recurrence rate and progression of this disorder versus unipolar disorders, physicians should expect to find significant social and occupational dysfunction (
Table). This finding is frequently evidenced by multiple failed interpersonal relationships, erratic career or job performance, financial difficulties, and legal problems, as well as serious high-risk behavior. Additionally, physicians should suspect bipolar disorder in patients who have antidepressant-refractory anxiety disorders, particularly panic and social anxiety disorder, as well as prior or active substance abuse.
11
A new, patient-rated screening instrument for bipolar I and II disorders, the Mood Disorder Questionnaire (MDQ) is available.
18 (A version derived from the original MDQ is available as a pdf file for downloading on the Depression and Bipolar Support Alliance's Web site at:
http://www.dbsalliance.org/questionnaire/screening_intro.asp). This instrument has been validated on an outpatient psychiatric population and found to have a sensitivity of approximately 70% and a specificity of 90%. A patient with depression endorsing 7 or more of the 13 items contained in question 1 of the questionnaire would suggest a diagnosis of bipolar disorder. The patient must then acknowledge on questions 2 and 3 that the symptoms endorsed in question 1 have co-occurred and admit that the symptoms have resulted in at least moderate social or occupational problems. In a busy clinical practice, this timesaving instrument can be a tremendous aid in diagnosis. Its use in mental health settings, as well as in primary care settings, should be strongly encouraged.