Treating Bipolar Depression: Part III

John McManamy Health Guide
  • Let’s review some of the main points from my two previous blogs:

    On one hand, bipolar depression appears to be a different animal from unipolar depression. On the other, some unipolar depressions have a cycling pattern that resembles bipolar. Accordingly, treating bipolar depressions as if they were unipolar depression can lead to disaster. Ironically, treating certain unipolar depressions as if they were unipolar depression can also lead to disaster.

    In terms of both efficacy and safety, antidepressants (the go-to med for unipolar depression) tend to be problematic for treating bipolar depression. Bipolar patients on antidepressants are at risk of switching into mania or rapid-cycling. There may be a time and a place for an antidepressant, but it is advisable to use them only in conjunction with a mood stabilizer, the American Psychiatric Association strongly recommends in its 2002 practice guideline for bipolar disorder.
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    Because of the cycling nature of bipolar (and some unipolar) depressions, there is a growing consensus that clinicians should have regard for treating the cycle rather than merely the symptom. Even in the early phase of treatment, when depression (or for that matter mania) may be raging fierce, clinicians need to be thinking ahead toward keeping the patient stable, and thus avoiding cycles back down into depression (which are far more common than cycles back up into mania).

    Until recently, only lithium was regarded as having utility for treating bipolar depression (though it is considered stronger against mania). Mood stabilizers (such as Depakote) and antipsychotics (such as Risperdal) earned their stripes battling mania.

    Lately, however, one antipsychotic and one mood stabilizer, plus an antipsychotic-antidepressant combo pill, have been pressed into service for bipolar depression.

    Before proceeding, once again the reminder that my MD stands for manic depression and not doctor of medicine. Please fully discuss matters with your psychiatrist before reaching any conclusions.


    Lamictal’s FDA indication is for bipolar maintenance treatment, not bipolar depression. The 2003 indication is based on two trials lasting 18 months (an eternity by meds trial standards). Lamictal proved superior to lithium at delaying relapses into depression in patients with bipolar I with recently occurring manic or hypomanic episodes, while lithium proved superior at staving off relapses into mania. The FDA did allow GSK to put on its labeling that the findings were more robust for bipolar depression treatment.

    Lamictal’s manufacturer, GSK, also tested Lamictal for treating depression in the short-term (what is called the acute phase), and achieved encouraging results in one published 1999 trial. But, according to trial data listed on GSK’s web-based clinical trial register, the drug failed to outperform the placebo in seven unpublished trials ranging from seven to ten weeks. One of these trials involved unipolar depression. Two were for recurring unipolar depression, the type of cycling depression considered by many a close cousin of bipolar depression. The other four trials involved populations with bipolar I and bipolar II depression.

  • What the complete clinical trial record tells us is that Lamictal is a mood stabilizer with demonstrated efficacy for preventing relapses into bipolar depression, but is not the equivalent of a short-term antidepressant. Your psychiatrist may have sound clinical reasons for going “short” with the med, anyway, but you are entitled to clear answers first.


    Eli Lilly’s Symbyax (combination Zyprexa and Prozac) was the first drug to actually receive an indication for bipolar depression (in Dec 2003), though the indication fails to distinguish between short-term and long-term treatment. Zyprexa is an antipsychotic first used to treat schizophrenia and later to treat mania. The indication was based on two eight-week trials showing a mean improvement of about 50 percent. The trials also showed that Zyprexa without the Prozac boost demonstrated a fairly strong antidepressant effect, as well. But with sales of Symbyax amounting to just $53.9 million in 2005 (compared to Zyprexa’s $4.2 billion over the same period), it is clear that Symbyax is not to be Lilly’s next blockbuster med.
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    In October 2006, the FDA approved AstraZeneca’s Seroquel for treating bipolar depression. The indication does not distinguish between acute (initial phase) and maintenance (long term) treatment. Like Zyprexa, Seroquel is an atypical antipsychotic first used to treat schizophrenia. In 2004, the FDA approved its use for acute mania. The latest approval was based on two eight-week clinical trials. Nearly sixty percent in both trials responded to the drug (ie a 50 percent or more reduction in symptoms) and some 50 percent remitted (a virtual elimination of symptoms). By the standards of clinical trials, these are considered outstanding results, which augur well for future sales.

    What to Make of the Evidence

    The clinical evidence points to the proposition that, for bipolar depression, the medication that gets you well may not necessarily be the one that keeps you well, unless it’s lithium. Seroquel and Symbyax have demonstrated their efficacy in the early going, but have yet to prove their worth over the long haul. The labeling on both meds warns of the potential dangers of long-term use due to risk of tardive dyskinesia and other side effects.

    By contrast, the weight of evidence does not support Lamictal as a short-term med, nor does it have an FDA indication for this purpose. On the other hand, the evidence suggests that this may be the drug that keeps you well.

    Another way of saying this is Seroquel or Symbyax (or perhaps just Zyprexa without the Prozac) for the short term, Lamictal for the long haul (keeping in mind lithium as an option for going both short and long). The final decision – which may be a completely different one – is a matter for you and your psychiatrist.

    There is no perfect med for bipolar depression, but we are getting a lot smarter about what to do. Please work on forging a strong working partnership with your psychiatrist, and do not forget about the many non-meds options discussed in Part II.

  • Find bipolar disorder drug information.
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    Learn more about treatment for bipolar disorder.

Published On: January 16, 2007