Lamotrigine & Melanin:Beta-blockers & Bipolar Disorder Treatment
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Q:  Lamotrigine & Melanin Beta-blockers & Bipolar Disorder Treatment

Dr. Phelps, I have two questions in regard to mood stabilizers or potential mood stabilizers: 1) Does Lamotrigine permanently bind to melanin receptors or does it clear out after a certain length of time? 2) I have seen Beta-blockers listed as potential treatment options for bipolar in some publications. Apparently, the theory is that these increase blood flow to the frontal lobes. Are these worth a try?


Dear Dan --

1.  Let's start with the beta blocker. I think what you may have run into, unless there is something out there I haven't seen yet, is that beta-blockers have been used as an augmentation strategy along with standard serotonergic antidepressants for the treatment of unipolar major depression.  Their effectiveness in this role has been debated for some time.  The current working impression is that they don't have much impact.  Interestingly, in response to your question, I discovered one article on the use of beta-blockers in bipolar disorder, suggesting that they might actually have an adverse effect (Yatham et al; I have not dug up the article itself to see what adverse effect they are referring to).

Whoops, hold it, maybe this is the article that spurred your question.  In February of 2008, in a European Journal, a group reported augmentation of paroxetine (trade name Paxil in the United States) with a beta blocker (pindolol). Although again they did not find that overall this augmentation strategy was more effective than a starting up paroxetine alone, the combined strategy (versus paroxetine plus placebo) did indeed help patients with bipolar depression.

In other words, in this 2008 study, some of the patients had bipolar depression, and some had unipolar depression.  In those with bipolar depression, when they were given paroxetine, they did better if paroxetine was combined with pindolol than if paroxetine was given alone.  Well, that's interesting. At this point, adding paroxetine for the treatment of bipolar depression is not a widespread strategy. So this paper may not have a great deal of impact (particularly in the United States, where a much larger scale study recently showed that paroxetine was no better than a placebo in patients with bipolar disorder (Sachs).

2. As for lamotrigine and melanin: nothing new -- I just looked, on Google and Pub Med -- since I wrote a response to a question about that in 2005. I presume that because there is still a one-liner about this on websites like, the issue keeps coming up. But there is really nothing to go on to substantiate concern about this possible connection.  As far as I know, the only place that any warning at all was raised about it is in the manufacturer product information.  As far as I can tell, that is what is quoting.  If you know of any other source of information on this issue, please let me know.

Dr. Phelps

Published November, 2008

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