Lamictal & Varying Treatment Guidelines
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Q:  Lamictal & Varying Treatment Guidelines

It appears that some of the enthusiasm for Lamictal may be diminishing, as reflected in the changes in the new (forthcoming) APA Guidelines. See, e.g.,  

I'd be very interested in any thoughts that you might have regarding (1) these changes in the Guidelines, and (2) relatedly, the recent studies that seem to raise questions concerning Lamictal's effectiveness. 

I ask these questions not simply as a matter of curiosity. I was recently prescribed lithium for bipolar depression (in addition to the Wellbutrin that I have long been taking), I have had significant problems with resulting "side effects" (mental fogginess, memory problems, etc.), and so I have been considering Lamictal as an alternative. 

Thank you very much in advance for any information and insight that you might be able to provide in regard to all of this.


Dear Robert --
Two studies have appeared recently that I think are the basis for this confusion about how effective lamotrigine (Lamictal) really is.

The bottom line: for patients who are more severely depressed when they enter a research study, lamotrigine is consistently found to be more effective than a placebo.  The results are crystal clear on this, as can be seen in a single graph to which I will leave you in a moment.

By comparison, when lamotrigine is used in patients who are not as severely depressed, but the results are not so clear.  Indeed, a rigorous interpretation would suggest that lamotrigine is no better than a placebo in such patients.

Finally, if you add all the patients together, in these studies -- the less depressed as well as the more severely depressed -- lamotrigine still looks better than a placebo, but not by much.

For the two studies in question, and the graph which displays all those findings described above, here is a link that attempts a translation of these two "meta-analyses": Does Lamotrigine Work, or Not? Don't get too lost in the details, if you find them overwhelming.  If necessary, just skip to the more important, more recent of these two studies.

Ironically, I think that what you are seeing in the varying Treatment Guidelines being published recently is a varying expectation for "sufficient evidence", rather than a varying view of what the medication actually does.  In other words, some treatment guideline authors have set the bar much higher for official evidence of a medication's effectiveness than other authors (including the older Texas Medical Algorithm, which put lamotrigine very high, but then was questioned in the McMan article you linked).

Thanks for the important question.

Dr. Phelps

Published June, 2009


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