Kindling & Refractory Bipolar Disorder
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Q:  Kindling & Refractory Bipolar Disorder

Dr. Phelps:

  I was diagnosed Bipolar I three years ago. I'm now 51 years old, and my first episode was severe depression at age eighteen.  My question is regarding the concept of "kindling".  My understanding is that as one progresses through life with the illness, without treatment, the tendency to have episodes and their severity increase over time.  Additionally, this may be partly to blame for treatment resistant "refractory" bipolar disorder.  As for myself, I am on a maintenance regimen of Lamictal 300mg/day and Seroquel 100mg/day.  I'm better, but still plagued by subsyndromal depressive symptoms, occassional brief but sharp depressions, and some fairly strong hypomanic spikes.  I've not had a full manic episode for over three years now, since my treatment began.  What are your thoughts on kindling and refractory bipolar disorder.  Thanks

Dear Mr. G. --

To have reached age 51 and be doing fairly well is a good thing.  From your description here, my first thought is that this is a discussion of how to optimize a regimen that is working, rather than a discussion of kindling and refractory bipolar disorder.  But perhaps I am being too optimistic in my interpretation of your description.

As you may know, the usual "top end" dose for lamotrigine (Lamictal) is 400 mg (and occasionally we go a little higher, although the risk of mild neurologic side effects such as memory problems and mild balance problems begins around 400 mg and goes up from there).  So there may be a little room to go up -- in discussion with your doctor, of course, not on your own.  As for quetiapine (Seroquel), here there is much more room to go up.  Indeed, the anti-manic dose is 600 mg in most studies, although I think it has the potential for such benefits at lower doses in some people. 

In general, I prefer to target "cycling" than either depression or hypomania. That way, any medication which can smooth out the pattern can be considered, not just those with specific antidepressant properties, or anti-manic properties.  In your case, both lamotrigine and quetiapine can be very effective "mood stabilizers".  As you also may know, lamotrigine is generally stronger against the depression side symptoms; and higher doses of Seroquel, closer to 600 mg, generally thought to have more strength against manic symptoms.

The point there is that just some further tuning of your current medications might get you a very nice result.  That way we would not have to talk about "treatment resistance", let alone "kindling".  But just two brief thoughts on the these issues: as long as there is no antidepressant in the picture, which can keep effective mood stabilizers from actually working, then in general the approach to "treatment resistant" bipolar symptoms is to keep laying on the mood stabilizers until things smooth out. Of course this includes non-medication approaches, including lifestyle changes (no alcohol, no stimulants, in some people no caffeine; a regular pattern of exercise; and very importantly, a regular pattern of sleep, even on weekends) and bipolar-specific psychotherapy.  The latter is not widely available but any very good psychotherapist can incorporate bipolar-specific tools easily into her or his practice; the link above is a summary of that field with references, to which you could direct your therapist.

Finally, regarding kindling: we must all remember that this is a theoretical concept.  I certainly worry about it, particularly in terms of antidepressants, but my opinions are not widely shared.  Here is my website page on kindling.

Again, in summary, based on the paragraph you sent (knowing it might be a good deal more collocated than this), if I was your psychiatrist I would be excited: "look, we've clearly made headway.  Let's just proceed along the same lines a bit further and see how much better we can get this just using your current medications.  Of course higher doses carry more risk of side effects, so there is always a trade-off.  Good luck getting that figured out --

Dr. Phelps

Published November, 2008


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