Treating Bipolar Depression: Part I
In October last year, the FDA approved Seroquel for treating bipolar depression. Currently, there are three medications on the market associated with treating bipolar depression, plus an old standby with some demonstrated effect for this phase of the illness. Now is a good time to review bipolar depression, and how precisely these meds (as well as antidepressants) are supposed to work.
This series of blogs is in three installments. Part I discusses bipolar depression and antidepressants. Parts II and III talk about various meds strategies for different phases of bipolar depression.
Before we proceed: My MD stands for manic depression, not doctor of medicine. The purpose of the following is to help you make informed choices, in partnership with your psychiatrist. In no way is the following to be construed as medical advice. Please fully discuss all matters regarding your treatment with your psychiatrist.
Depression is by far the more prevalent and incapacitating form of bipolar disorder. According to Stanley Foundation Bipolar Network data, bipolar I patients are depressed three days for every one day manic or hypomanic while bipolar II patients are depressed 50 days for every one day hypomanic.
There is strong evidence that many so-called “unipolar” depressions exhibit the qualities of “bipolar” depressions. These are referred to as “highly recurrent” depressions that patients tend to cycle in and out of. These patients may not cycle “up” to the type of hypomania that is the diagnostic threshold for bipolar II, but they may exhibit some under-the-radar tendencies such as staying hypomanic for only a day or two (instead of the minimum of four days mandated by the DSM). Reclassifying these patients as true bipolars could conceivably widen the official bipolar population from two percent to as high as six percent.
Unipolar and bipolar depression may be close diagnostic cousins, but in terms of treatment they are very different. Bipolar patients tend to get misdiagnosed with unipolar depression, and are invariably subjected to endless trials on antidepressants which invariably fail them or even make them worse. If they are lucky, their psychiatrists will wise up and rediagnose them as bipolar. Another alternative is to treat patients with highly recurrent depressions as if they had bipolar disorder.
Confused? Read on
Antidepressants are standard treatment for unipolar depression. For bipolar depression, it is a different story. The American Psychiatric Association’s 2002 Treatment Guideline for patients with bipolar disorder recommends using antidepressants only with a mood stabilizer (such as lithium or Depakote). Without a mood stabilizer, there is a serious risk of a bipolar depressed patient switching into mania or hypomania or rapid-cycling. Even with a mood stabilizer, some psychiatrists regard an antidepressant as problematic.
There is no strong clinical evidence for treating bipolar patients with an antidepressant, even with a mood stabilizer. The drug company-sponsored antidepressant trials that have been carried out on large populations of patients with unipolar depressions have never been conducted on those with bipolar depression. This applies to both short-term treatment and long-term treatment.
One retrospective study of Stanley Foundation patients did find some benefit in patients remaining on their antidepressant, but this applied to only 15 percent of the patients in the study. Now if researchers could only figure out in advance which 15 percent.
What to Make of the STAR*D Findings
This year, the NIMH began releasing the results of a series of real world clinical trials known as STAR*D. A population of 4,000 patients with unipolar depression were first tried on an antidepressant. Those who failed on the antidepressant were tried on a different antidepressant treatment, and those who failed on the second antidepressant treatment were tried yet again on another, and so on to four rounds of treatment.
Of those who stayed in the study, 67 percent remitted. After two failures, the success rate dropped off sharply. These are the “official” results of the trials. The world’s leading authority on bipolar disorder, however, had a different take. In correspondence to me, Frederick Goodwin MD, co-author of “Manic-Depressive Illness” and former head of the NIMH pointed out to me that most of the patients in the study had experienced six or more depressions. In other words, their depressions fell into the “recurrent” rather than “chronic” category.
The cycling nature of these depressions may account for why so many patients in the study kept failing on their antidepressants or dropped out of the study in apparent frustration. These patients may have benefited from treatment as if they had bipolar. Unfortunately, STAR*D did not test for this.
Next: Treating the cycle rather than the symptom …
Published On: January 08, 2007
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