Rapid-cycling, or refractory, bipolar illness

Rapid-cycling does not mean that your moods cycle rapidly.  That is English, not science.  Rapid-cycling, in the scientific use of the term, means having four or more mood episodes in a year.  That means that the episodes can last 3 months.  This is not about your moods “cycling” over hours. That’s mood lability, which is part of mixed states, not rapid-cycling. The difference is important.  Rapid-cycling is often missed because clinicians don’t pay attention to the fact that patients have episodes lasting a few weeks, a few times in a years.  That’s rapid cycling.

The importance of the diagnosis is that it means that there is an ABSOLUTE contraindication to the use of antidepressants, under any circumstances, at all. This is because antidepressants cause rapid-cycling; they worsen it.  Put another way, the only intervention shown to improve rapid-cycling is antidepressant discontinuation, as described below.

If antidepressants are stopped or aren’t being used, one is still faced with the reality that rapid-cycling is a major poor prognostic factor. It was originally defined in people who didn’t respond to lithium.  So lithium is ineffective by itself. Clinicians falsely believe that anticonvulsants are more effective than lithium in rapid-cycling. This has never been shown; in fact, it’s been disproven.  Lamictal was studied and proven ineffective, equal to placebo, in two randomized trials of rapid-cycling (one of which was never published).  Valproate was shown to be equal to lithium in the largest randomized trial of rapid-cycling.  Carbamazepine also is equal to lithium in rapid-cycling in head-to-head.

In short, nothing works in rapid-cycling – except stopping antidepressants.  After that, since no single mood stabilizer is effective, it is logical to combine mood stabilizers.  Valproate plus lithium have been proven more effective together than when used alone.  Thus, I recommend combining those agents (or carbamazepine plus lithium) for  rapid-cycling. Usually, patients tend to need one dopamine blocker added to two standard mood stabilizers.

Even so, improvement in rapid-cycling is slow, and should never be judged on the basis of what happens over a month or two with a current mood episode.  One can assess efficacy only by seeing if 4 or more mood episodes in a year decrease in frequency. This means one has to look at multiple episodes, over 6-12 months, before efficacy in rapid-cycling can be evaluated.  This requires patience on the part of patients and clinicians Use multiple mood stabilizers, with or without dopamine blockers, and stay off antidepressants/amphetamines definitively.  And wait.  That’s the only way to improve rapid-cycling bipolar illness.

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