Nassir Ghaemi, MD, MPH


July 10, 2013

At the recent American Psychiatric Association (APA) meeting in San Francisco, California, a number of symposia addressed bipolar and depressive conditions.

Canadian researcher Roger McIntyre presented new analyses[1] of the neuroleptic lurasidone, in which its benefit in acute bipolar depression had been demonstrated. McIntyre looked at the effects of lurasidone in acute bipolar depression without any manic symptoms (what I call "pure" bipolar depression) vs depression with some manic symptoms (what some researchers call "mixed" bipolar depression). (The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, [DSM-IV] definition of major depressive episode is so broad that patients can have multiple manic symptoms and not meet the definition of a mixed episode if the overall duration of manic symptoms is less than 1 week. About one half of depressive episodes in bipolar illness involve some manic symptoms; the other half are "pure" depression, without any manic symptoms.) McIntyre's analysis found that lurasidone was equally effective in pure bipolar depression as in mixed bipolar depression. This finding suggests that the benefits of some neuroleptics are not only for mixed states but also for pure depression.

In another presentation, Dr. Sheri Johnson, of the Department of Psychology at the University of California, Berkeley, described studies examining ambition, using rating scales, in persons with bipolar illness vs controls.[2] People with bipolar illness had more ambition in their life goals than controls, and higher ambition correlated with higher risk for later manic episodes. This negative relationship should be balanced by the observation, however, that many persons with bipolar illness achieve their ambitions and are highly represented among successful entrepreneurs, as described by Dr. Michael Freeman of the University of California, San Francisco.[2] Dr. Terence Ketter, of Stanford University, Stanford, California, also described research[2] showing that persons with bipolar disorder in the euthymic mood state demonstrated higher creativity, in tests of creativity, than normal controls. Creativity was higher among students in the creative professions (art, writing) than normal controls, but it was even higher among persons with bipolar illness than in normal controls.

Another session examined recent biological and course studies. John Geddes, chairman of Oxford University's Department of Psychiatry, Oxford, United Kingdom, described new prospective course data[3] showing that the natural history of bipolar illness is not characterized by periods of normal mood alternating with periods of abnormal mood episodes of opposite polarity (ie, depression or mania), as claimed by the DSM system. Rather, bipolar illness is characterized by frequent mood lability, with both manic and depressive symptoms, that are sometimes milder (during periods outside of clinical mood episodes) and sometimes more severe (during periods meeting clinical mood episode criteria). In other words, mood episodes, when they occur, usually involve a mix of depressive and manic symptoms, not pure depressive or manic episodes, as claimed by DSM. Further, these mixed episodes occur on a baseline temperament often characterized by mild mood lability (as in cyclothymic or hyperthymic temperaments), not completely normal euthymic mood. This constant mood lability throws into doubt the entire DSM-based distinction between "bipolar" and "major depressive" disorders. It is instead consistent with Kraepelin's original view of manic-depressive insanity as a broad illness of recurrent mood episodes, irrespective of polarity (in other words, recurrent depression is manic-depressive illness even without classic manic episodes), in contrast to the current faith in bipolar disorder (mania is required) vs major depressive disorder (mania is absent).

Other symposia either directly or indirectly addressed the unavoidable fact that DSM-5 was released at the APA meeting, and there was debate about whether the DSM approach to psychiatric nosology should be continued for another 30 years or not.[4] In a symposium on the debate about antidepressant efficacy in major depressive disorder, I commented on the meta-analyses that indicate that antidepressants are differentially effective vs placebo based on severity of depression: Antidepressants and placebo are equally effective in mild depression; benefit with antidepressants is seen only in more severe depression. I suggested that the broad major depressive disorder category in DSM-III onwards obscures antidepressant efficacy because many different types of depression are lumped together, while antidepressants may be responsive in some but not other kinds of depression. An impassioned debate about the relative merits of DSM-5 ensued.

The APA meeting in San Francisco, from the standpoint of mood illnesses, demonstrated that there is no consensus about what we know and what we don't know. Whether DSM-III through 5 has helped us progress in our knowledge on these topics also appears debatable. Recent studies described above suggest that there is room for doubt.


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