Letters to the Editor
High Frequency of Bipolar Spectrum in Outpatients With Depression
The frequency of bipolar II disorder (BD II) is higher than the 0.5% community prevalence reported in DSM-IV-TR (1): rates are 11% in the community (2,3) and 30% to 60% in outpatients suffering from depression (4,5). Diagnostic criteria for “bipolar spectrum disorder” (6) include major depressive episode (MDE), no spontaneous mania or hypomania, family history of BD, and (or) antidepressant- induced mania or hypomania, plus some of the following: hyperthymic personality, many MDEs, short-duration MDEs, atypical and psychotic features, young and postpartum onset, short-duration antidepressant response, and no response to many antidepressants. The diagnosis of depressive mixed state (DMX), defined as MDE plus 3 or more concurrent hypomanic symptoms, has received clinical, family history, and psychometric validation (7–9) and replication (10,11). DMX is common in patients with BD II (up to 60%) and in MDE outpatients with major depressive disorder (MDD) (up to 30%). Links between MDD with DMX and BD II have been found (specifically, similar age of onset, atypical features, and bipolar family history) (7), supporting its inclusion in the bipolar spectrum (4,5). The current study aimed to determine the frequency of the bipolar spectrum in outpatients with depression, including bipolar spectrum disorder, MDD with DMX, and BD II.
Details can be found in previous reports (7–9). A sample of 433 MDE outpatients consecutively presenting in private practice (which is more representative of mood disorders treated in Italy) were interviewed with the Structured Clinical Interview for DSM-IV–Clinician Version (12), as modified by Benazzi and Akiskal (13), to focus probing for past hypomania more on overactivity (that is, increased goal-directed activity) than on mood change. Patients with the following conditions were excluded: substance- related and borderline personality disorders (rare in the setting) (14), significant general medical illnesses, and cognitive disorders. Often, family members or close friends supplemented clinical information. We investigated the BD I and II family history of first-degree relatives, using the Family History Screen (15). We defined DMX as MDE plus 3 or more concurrent hypomanic symptoms (7–9). Diagnostic criteria for bipolar spectrum disorder were followed: family history of BD, more than 3 MDEs, atypical features, and onset of first MDE before age 25 years. We used the t test to compare means (SDs) and the 2-sample test of proportion to compare proportions. We calculated 2-tailed P < 0.05.
Of 433 patients, 260 (60%) suffered from BD II. Patients with BD II, compared with those having MDD, were significantly younger (mean age 41.7 years, SD 14.0 vs mean age 47.0 years, SD 15.6), had a lower age of onset (mean age 22.9 years, SD 10.8 vs mean age 32.0 years, SD 14.5), had a higher percentage of more than 3 MDEs (81.1% vs 58.9%), and had a higher percentage of atypical features (53.0% vs 25.4%), DMX (59.2% vs 29.4%) and family history of BD (54.1% vs 21.3%). In the sample with MDD, 17.9% suffered from bipolar spectrum disorder. When we added BD II and bipolar spectrum disorder, bipolar spectrum frequency was 67.2%. When we added BD II and MDD with DMX, bipolar spectrum frequency was 71.8%.
We found high bipolar spectrum frequency according to 2 different definitions. The high frequency of BD II vs MDD was probably related to interview methods (13), which may have important treatment implications. Underdiagnosis of the bipolar spectrum can lead to underuse of mood stabilizers and to overuse of antidepressants (6). Overuse of antidepressants in treating BDs may increase mood instability.
Validated interviews, standard and systematic assessment, key informants, and an interviewer with clinical and research experience in mood disorders should have reduced the possibility of BD II overdiagnosis (BD II frequency was in the reported range; 4,5).
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Franco Benazzi, MD,