Q:  Lamictal & Lesions

Dr. Phelps,

I was diagnosed with bipolar II several years ago and think that my disease state is pretty mild (mania wise the depression gets pretty bad).  One drug that worked very well for me in the past was lamictal.  I was on up to 600 mg a day at one point and doing well. 

I then developed signs of SLE with an ana titer of 1:1280.  So my primary doctor was worried that it could be drug induced lupus and talked with my psychiatrist to discontinue the lamictal.  Hoping it was I was off the lamictal for almost 2 years.

Even though I tested positive for anti-ds dna antibodies specific to SLE and not found in drug induced lupus.  

I decided to restart the lamictal because I was getting really depressed and it is really a good drug for me.  I was switching psychiatrists at the time. 

I did the normal tapering up, using an old (yet not expired) supply (cutting 100's into quarters at first) - because I was waiting to see the new psychiatrist. By the time I saw the new doctor I was up to 100 mg a day. 

about two weeks after making it to 100 mg I developed what I originally thought was acne.  But what was strange was it was not behaving like acne.  I usually get acne before my menstrual cycle, and this was day 15 or a normally 31 day cycle.  They also did not pop.  They would white, but the "whiteness" was dead skin.  They were  all over my chin, some one my cheeks, and some on my chest.  I also had what looked like a cold sore on my lip, but it wasn't where I usually get cold sores.  And I also has "canker" like sores around some teeth on my gums in my mouth. 

So I decided to find out what steven johnson syndrome really is on the internet.  I  knew it was a rash but I wanted to see how it presented.  After looking into it I started to become concerned, but since lamictal works so well, decided I would see if it goes away and cut back the dose.  Well the next day my face and mouth were on fire.  I called and left a message with the psychiatrist and stopped the lamictal.  (I have yet to hear back from the psychiatrist and it's been about 3 weeks).  I since then canceled my appointment due to my expectation if she is to "manage my meds" she should respond. 

The lesions have now gone away.  I still have some healing scabs.  But I don't know if it really was steven johnson syndrome, because I never saw the doctor.  And I'm worried if I try lamictal again that it could come back worse.  Even though I really feel like lamictal is the drug that works for me.  I've looked into it some, and it seems as though lamictal has not been successfully restarted.  And I really don't want to risk going blind, if the lesions happen to appear on my eyes next.  

So I'm wondering what you think of all this.  If it's likely steven johnson syndrome (which obviously you didn't see it so how would you know for sure) - but neither did any other doctor.  And whether lamictal is out of the question forever. 

So I'm currently in search of a new psychiatrist of which is not becomming a very successful endeavor, as I'm very not "therapy/psychiatrist" friendly.  I give them a hard time, because I don't trust them.  

Thanks,
Dana

Dear Dana -- 
Rather than tell you what that was, which as you point out, not having seen it, how would I know? -- I'll tell you about some of the cases I've seen that were worrisome enough to stop the medication and have no intention of re-trying it, even with the microdose/slow titrations which some people have successfully used to restart lamotrigine (Lamictal) after a rash was seen. I think what you'll see here is that what you had is close enough to the "big worry" that you'd probably better keep hunting for an alternative medication as well as an alternative psychiatrist. 

The closest case I've had to what you describe was a woman taking not lamotrigine but zonisamide (Zonegran), a medication also known to have the potential to cause Stevens-Johnson Syndrome (SJS). The risk of SJS with zonisamide is much higher if someone has had an allergic reaction to a sulfa-based medication such as sulphamethoxisole (e.g. Bactrim or Septra -- sulfa-based antibiotics), which indeed this woman had experienced. We only tried zonisamide because we had tried so many other medications. She had a great response to quetiapine (Seroquel) but her glucose was going way up so we stopped that, and she was much worse again. So, after a long discussion about risk and how we were going to watch for rash, etc., we started Zonegran. After about 3 weeks she emailed me and said she had sores inside her mouth. She said her mouth was "raw", and that it felt like it was on fire. She know she had waited too long to let me know. I told her to stop as of that moment. The whole thing got a little worse, after that, then slowly got better.  I think we dodged the big bullet there: I think that was SJS getting started. I've had no such cases using lamotrigine, but statistically I'd have to have used it at least 1,000 times to have seen one, and I'd guess I'm somewhere in the 700-800 range so far. 

However, I've had three cases of less dramatic rash-like phenomena on lamotrigine, and sent all of them to a dermatologist. In two cases, he said "stop", indicating that indeed we could be looking at the beginning of something like an SJS reaction. One women had blisters on her hands, about 3 weeks as I recall after starting lamotrigine (I usually start at 12.5 mg for a week and increase by that increment weekly; sometimes I start as you did with 25 mg for two weeks, then 50 mg for two weeks). Nothing in her mouth, but that was enough for the dermatologists to say "quit". The other woman had a red spot on her cheek, not in or near her mouth.  We watched that one and continued the medication, but when she got a similar one on her shoulder (meaning that she clearly was having some "systemic", not local-spread phenomenon), I sent her and she too was told to stop.  I had one other case that worried me but the dermatologist said was okay, and we continued without incident.

What you're describing here is basically the worst case I've ever directly experienced (as opposed to those cases that are described in the literature but which I've never had anything to do with, where obviously they've gone on to full-blown SJS, which as you've learned can be a life-threatening condition and in most cases requires hospitalization with treatment as though for severe burns). I would be petrified to participate in a re-try of lamotrigine in your case. I might still do it, if you and some skin expert with a lot of immunology experience were to decide it was okay to do, because I know what the symptoms of bipolar disorder can be like and what risk is therefore sometimes justified if no alternatives are working --  but I'd still be petrified and would insist on an ultra-low dose approach (like the 0.1 mg doses used in one study: Besag. Note in that study that all those re-exposed had a mild rash at first and yet still they used this ultra-cautious dosing).

I hope you're getting the level of fear here. I think at minimum we could say that you should not even contemplate a re-try without a very satisfactory consultation with that skin/immunology expert. Sorry to have to say that. You've probably seen the data on fish oil, which occupies a similar niche to lamotrigine re: more effect on depression, it appears, than on hypomania, but maybe also some anti-cycling potential.  I'm going to put this on my site but haven't gotten to it yet so will for now just append it here, used with permission -- a testimonial about fish oil to increase your level of interest. Good luck with the hunt. 

Dr. Phelps

A fish oil testimonial: 

My diagnosis hx (20 years):

> Axis I: Bipolar II, Rapid Cycling Type

> Axis II: Borderline Personality D/O

> Axis III: Premenstrual Dysphoria

I've never responded well to medication. I "self-medicated" for years with alcohol and drugs, and have never had an enduring stable relationship with anyone until recently. I am [around 40] years old, a master's level social worker, and, as an aside, very physically fit (exercise being another "self-medication" technique).

In addition to the above, I've tried everything to stabilize my moods, including psychotropic medications and a multitude of supplements. Over a year ago I stopped drinking and became an active member of AA. Though the fellowship has helped to reinforce my confidence in practicing new learned behavior, my mood lability, borderline and PMS symptoms, have persisted.

Four months ago, I began taking Omega-3 fatty acids (360 mg/EPA and 240 mg/DHA twice daily (after breakfast and after dinner). In this past 4 months my relationships with others have improved in ways I could not have imagined, and the emotional reactivity and instability. 

I have always experienced in response to the smallest of stressors has all but disappeared. I have thought of stopping the supplements just to prove a point, but I hate to look a gift horse in the mouth. For the first time in my life, I don't swing up and down and I am dumbfounded. 

There are times I feel like I must be a poster child for Omega 3's. I realize that I have been more conscious of my behavior and have worked to be more mindful of my emotional reactions. But I'm not convinced I could have arrived at this relatively neutral/rational emotional place without the inclusion of Omega-3's.

At my request she wrote back, giving permission for me to use this statement, and added: 

Published June, 2006