Bipolar disorder in primary care: the bipolar spectrum is larger than was once believed, and misdiagnosis can lead to an unfavorable treatment response

Journal of Family Practice, March, 2003 by J. Sloan Manning

Antidepressant monotherapies induce remission far less often than was initially believed--usually in <45 to 50% of cases in controlled trials. (1) This means many depressed patients have impairing residual symptoms that increase their risk of relapse.

Difficult-to-treat depression is also common. Many patients fail multiple antidepressant trials; others respond quickly and robustly, only to abruptly lose treatment benefits after a few weeks. Antidepressants cause some depressed patients to deteriorate by triggering or worsening symptoms of activation--restlessness, insomnia (often with racing thoughts), agitation, irritable mood, impulsivity, and--in rare cases--increased suicidality.

Undiagnosed bipolar illness is the cause of many of these difficult-to-treat depressions. (2) Few patients with bipolar disorder feel the need to seek medical attention when they are hypomanic or manic; they are much more likely to present with depression. Their paradoxical responses to antidepressant monotherapy are typical of hypomanic/manic "switches" or mixed states (concurrent mania and depression).

Depression is common in primary care practice, with perhaps 20% of all patients affected by some mood disorder. In generalist settings, depression was once considered overwhelmingly unipolar, but recent evidence suggests that up to 30% of depressed and/or anxious patients in primary care may have bipolar illnesses.

As awareness of a prevalent bipolar spectrum has grown, psychiatrists are changing their approach to patients with depressed and/or anxious mood and are emphasizing the exclusion of bipolar disorder prior to prescribing antidepressants or other medications. This article is intended to help clinicians differentiate unipolar from bipolar illness in patients who present with symptoms of depression.

Defining the bipolar spectrum

Bipolar disorder is characterized by periods of expansive or irritable mood known as mania or hypomania. (3)

* A diagnosis of bipolar I disorder requires at least one manic episode.

* Bipolar II disorder is defined as hypomania plus at least one episode of major depression.

* Patients with cyclothymic disorder experience hypomania and depressions that do not meet criteria for major depression.

* A residual category referred to as bipolar not otherwise specified (bipolar NOS) is used for patients identified by clinicians as having bipolar illness but not meeting formal criteria for other categories.

Substantial research since DSM-IV was published in 1994 suggests that bipolar NOS encompasses many cases that are indistinguishable from bipolar II disorder, based on the duration of hypomanic episodes.

Changing prevalence. Earlier studies estimated the prevalence of bipolar I (manic) illness in the 1% range. When bipolar II or related illness is included, the range expands to 3 to 6%, with some estimates even higher. A figure of 5% is considered reasonable. (4) This universe of bipolar illness is often referred to as the bipolar spectrum.

Prevalence in primary care. One-third of depressed patients arc treated in mental-health settings, (5) and two-thirds are cared for elsewhere--usually in primary care. In the best cross-sectional investigations done during the 1980s and early 1990s, Coyne et al (6) documented bipolar illness in 10% of primary care patients with depression, using the structured clinical interview. Manning et al (7,8) documented a bipolar prevalence of 25 to 30% in primary care cohorts of depressed and anxious patients (Figure 1).

[FIGURE 1 OMITTED]

Presentation of bipolar disorder

Bipolar II depression is the most common clinical presentation of bipolarity. Before you select treatment for any depressed or anxious patient, it is wise to exclude bipolar illness. The following scenarios should raise suspicion for bipolar illness:

Antidepressant failures. Consider three or more antidepressant failures a diagnostic clue. The same is true for anxiety disorders, which commonly coexist with bipolar illness.

Antidepressant-induced activation. Antidepressant-resistant panic disorder and generalized anxiety disorder may indicate the presence of bipolar disorder, especially when antidepressants induce activation symptoms, restlessness, irritability, and insomnia or worsen panic attacks despite low starting dosages and slow titration.

Behavioral disruptions. Persons with evidence of behavioral disruptions (tempestuous interpersonal, legal, or occupational histories) and attention-deficit/hyperactivity disorder also should be closely examined. Many clinicians may be more familiar with DSM-IV axis II personality conceptualizations, but the high comorbidity of bipolar disorder with borderline personality disorder and other members of the "erratic" cluster is noteworthy.

Early diagnosis is important, because patients with bipolar disorder may respond adversely to antidepressants (particularly when used as monotherapy), anxiolytics, and psychostimulants when these agents are used as unfocused interventions. For example, treatment-emergent hypomania/mania, rapid cycling and mixed states, and resistance to eventual treatment with mood stabilizers have been seen. Therefore, rather than introducing antidepressant therapy for depressed patients with bipolar symptoms, it may be psychopharmacologically prudent to begin therapy with a mood stabilizer.