Overview of Mixed Depression in Italy

By Franco Benazzi, M.D. | April 15, 2004

The presence of hypomanic symptoms in MDD supports the continuity between MDD and BD-II (Benazzi, 2003d). The distribution of the number of hypomanic symptoms between BD-II and MDD was near normal, not supporting the two depressive syndromes as distinct disorders (i.e., categories). Following Kendell and Jablensky's (2003) approach to diagnostic validity, points of rarity between the two syndromes would support a categorical definition. By applying this method to a sample of patients with mixed depression, a near normal curve of hypomanic symptoms was found, supporting our dimensional definition of mixed depression.

The bipolar nature of mixed depression, studied in mixed BD-II and MDD samples, was strongly supported by a high family history of BD. Family history was assessed by interview of probands (and often of a family member) by the Family History Screen. This structured interview has the important advantage of assessing both BD-I and BD-II in first-degree relatives. There was a high frequency of BD-II in the probands of patients with mixed depression and a similarly high frequency to that of probands of patients with BD-II. Currently, family history is probably the most important diagnostic validator (Akiskal and Benazzi, 2003; Ghaemi et al., 2002).

The diagnostic validity of mixed depression was supported by its association with classic bipolar disorder and diagnostic validators (Akiskal, 2003; Akiskal et al., 1995; Angst et al., 2003; Ghaemi et al., 2002; McMahon et al., 1994). The diagnostic validity and bipolar nature of mixed depression was also supported by finding a dose-response relationship between the number of hypomanic symptoms present during the depression and positive family history of bipolar loading.

The bipolar nature of a subtype of mixed depression, i.e., psychomotor agitated depression, was supported by its links with bipolar validators. Mixed depression was found to be very common in BD-II samples (around 60%) and in MDD samples (around 30%), supporting its diagnostic utility (Benazzi and Akiskal, 2003c). The most common hypomanic symptoms during mixed depression were irritable mood, racing thoughts, psychomotor agitation, talkativeness and distractibility. An important finding was the positive association between racing thoughts and suicide ideation. Our studies on the increased mental activity of mixed depression were not limited to racing thoughts (increased speed of thoughts). We also included "crowded thoughts" (mind full of non-stop thoughts). This link between racing or crowded thoughts and suicide ideation could explain why treatment of mixed depression with antidepressants sometimes led to suicidal behavior, probably by increased mental and behavioral agitation (Benazzi, 2003e; Koukopoulos and Koukopoulos, 1999).

Temperamental mood lability was found to be more common in mixed depression than in non-mixed depression, suggesting that frequent baseline mood swings may facilitate the onset of mixed depression by pushing hypomanic symptoms into depression. Akiskal et al. (1995) already showed that mood lability predicted the shift of MDD to BD-II. Mixed depression, as compared to non-mixed depression, was more likely to occur in females and at a younger age (Benazzi, 2002b). Mixed depression was found to be no more common in BD-II with hypomania-depression cycles versus BD-II without these cycles.

The impact of treatment on our mixed depression study suggests that the current underdiagnosis of BD-II could be overcome by systematic probing for a history of hypomania and improving clinicians' interviewing skills. The interview should focus on assessing any history of overactivity rather than on mood change (behavior is easier to remember and is observable and verifiable by others). Negative outcomes of antidepressant treatment (without mood stabilizers) of BD-II misdiagnosed as MDD could thus be avoided. Some of these unwanted effects include switching to hypomania, increased cycling, induction of hypomanic symptoms during depression and increased severity of mixed depression (Altshuler et al., 1995; Ghaemi et al., 2003; Koukopoulos and Koukopoulos, 1999). By diagnosing mixed depression, the possible negative outcomes of antidepressants used alone, such as increased agitation, racing thoughts, and irritability, anger and aggressivity, could potentially be avoided.

Dr. Benazzi is senior staff psychiatrist in the department of psychiatry, National Health Service in Forli, Italy, and director of the E. Hecker Outpatient Psychiatry Center in Ravenna, a collaborating center with the University of California at San Diego.

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Overview of Mixed Depression in Italy

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