# Lamotrigine



## optimusrhyme (Aug 24, 2004)

Sierra M, Baker D, Medford N, Lawrence EJ, Patel M, Phillips M, David AS (2004 submitted) Lamotrogine in the Treatment of Depersonalisation Disorder. Journal of Psychopharmacology.

Depersonalisation disorder (DPD) is the persistent subjective experience of unreality and detachment from the self. To date there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous double-blind randomised crossover trial although open trials were encouraging. We carried out an open label trial of lamotrigine in patients with DPD seen in a specialist clinic. The majority were also receiving other medications, mostly selective serotonin re-uptake inhibitors. 32 patients agreed to participate and had complete follow-up data. 16 (50%) showed a significant improvement (mean 40%) in their depersonalisation symptoms, as rated by standard and novel scales, assessed 16.6 months after commencing treatment. Concomitant symptoms of depression also showed improvement but this did not account for the specific effect on DPD. There were no serious adverse effects. The results of this trial suggest that a significant number of patients suffering from DPD may respond to lamotrigine, particularly when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotrigine as ?add-on? treatment in DPD.


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## dalailama15 (Aug 13, 2004)

I have all the core DP symptoms (constant and long-term) and I'm now into the third month of Lamictal (lamotragine) along with Wellbutrin. And so far nothing.

I am perhaps a little more detached from my daily behavior, and I have bits of songs in my head any time I am not really concentrating on something else. Also my dreams seem a little. . . dead, with quite a bit of just verbal stuff. I have no idea if this is connected to the combo, or really, how new these things even are.

At any rate, I will see the mental health professional who can write scrips in three weeks or so, and plan on switching to a regular SSRI, to augment the lamotragine, instead of the Wellbutrin.

I've got to pick one. You guys think prozac?

Which SSRI do yall think would be best for this last phase of this experiment?

Thanks

your friendly neighborhood dalailama


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## Guest (Aug 28, 2004)

By the way, Dali, your post made me laugh re the Idiot I was calling myself for not knowing how to delete a post I'd made in error (it was since deleted for me by Rev, but I read your funny response first, grin)

I'd say Prozac, only because if you can tolerate Wellbutrin and it doesn't make you jittery, etc. and in fact, you still feel deadened on it, then you'll need the most "stimulating" of the ssri's which is Prozac.

Have you tried any of the old anti-d's, the tricyclics? Just a hunch. You might ask the doctor about them.

Peace,
J


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## Homeskooled (Aug 10, 2004)

Dear Dalailama, 
I posted a poll some time ago on which meds had helped people with DP the most ( it was for a school project), and the most people seemed to be helped by Celexa, followed by Effexor. I think that if you were going for most good effects and least bad, Celexa would be the first I would try. Ron from the MSN depersonalization board attributes his cure to that and Klonopin. Good luck!

Peace 
Homeskooled


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## university girl (Aug 11, 2004)

Hey all,

I have been doing some reading up on lamotrigine. Since it seems to block the effect of ketamine, an NMDA antagonist, and because THC is also an NMDA antagonist (which is what triggered my DP/DR), I think I will try it out. I'll let you all know how it goes. I know study results have been quite contradictory but hey, it's worth a shot.

Uni-girl


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## dalailama15 (Aug 13, 2004)

Uni-girl
I'll keep you posted on my trial as well.

I probably should start a new thread on this, but the start of my severe and chronic _depersonalization _(not anxiety, not depression) is also, by all evidence, at least _connected_ to THC (and I know it is more than that.)

I agree with Uni-girl. There are real clues, suggesting real therapies, in the bio-chemistry of THC. For example



> Anandamide (N-arachidonoylethanolamine) is a brain chemical that activates the same cell membrane receptors that are targeted by tetrahydrocannabinol, the active ingredient in marijuana and hashish. The pharmacological effects of anandamide suggest that it may play important roles in the regulation of mood, memory, appetite, and pain perception. It may act as the chief component of a novel system involved in the control _of cognition and emotion_. [my italics]


http://www.nsi.edu/research/e008.html

To be clear, this system of anandamide receptors is usually called the cannaibinoid system.

And this, from _Nature_, titled
_*
The endogenous cannabinoid system controls extinction of aversive memories.*_


> Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom1. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction2, its cellular mechanisms are largely unknown. . . .
> Here we show that the endogenous cannabinoid system has a _central function in extinction of aversive memories. . . _ [my italics]


http://www.nature.com/cgi-taf/DynaP.../nature00839_fs.html&dynoptions=doi1093749359

http://www.letfreedomgrow.com/cmu/cannabinoids_and_bad_memories.htm

[edited this, delete paragraph, because it sounded a little defensive to me, and inappropriate when asking for advice from so many of you that I like and respect]


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## dalailama15 (Aug 13, 2004)

And Janine, thanks for the info on prozac, as well as the tricylic suggestion. I _have_ seen some stuff that suggests the possible efficacy of tricyclics, and with this additional evidence, I will discuss this with the MHP (mental health professional) during our next visit. And Homeskooled, I appreciate your imput as well.

And thanks to anyone else who may also respond to this issue. :!:


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## university girl (Aug 11, 2004)

dalailama,

in terms of what ssri you should try, i would personally recommend paxil as it did help me with my THC-induced dp/dr. thanks for the info on the research you mentioned above. i actually have quite a few papers on cannabinoid receptors etc and am learning more about the action of THC each day. not sure how it could induce a permanent change in neurobiology though...

uni-girl


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## dalailama15 (Aug 13, 2004)

> not sure how it could induce a permanent change in neurobiology though


My pet hypothesis is something like:

The storing and retrieving of emotional memory, the connecting of emotional memory to factual memory to consciousness, and the hard wired four F physiological and behavioral responses (fight, flight, feed, and reproduce) all are mediated through the limbic system, specifically the amygdala and hippocampus.

Since anandamide resides in these places and is connected to THC, by using common receptors, and since anandamide is implicated in the areas of malfunction I experience (emotional deadness, no sense of a continuous memory, etc.) the drugs (in my case THC) may have somehow gunked up these receptors, due to perhaps a genetic predisposition, or perhaps a predisposition created by the burning in (perhaps through obsessive repetition) of emotional distress. Or perhaps this gunking up somehow mimics a burning in of severe distress (severe enough to prevent its extinction in memory)

Or perhaps a burning in, or a predisposition, created by the kinds of things that Janine has talked about: the creation of an idealized self which supplants the real self, and which progressively becomes more and more detached from the real world, through distorting self images and expectations, and distorting reality to bend to its wishes..

Of course this is shakey, incomplete, and probably either obvious or silly since my knowlege of even basic biology is not very strong, and so my self-education in molecualar biology is going a little slow. :shock:


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## bat (Aug 18, 2004)

sertraline (lustral, zoloft) seems to be working for me although its been a nightmare to get on


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## gimpy34 (Aug 10, 2004)

Dalailama, what dose of Wellbutrin are you taking? I had been taking 300 mg a day forever. When Wellbutrin XL came out, I jumped up to 450 mg a day, split in two doses, and there was a world of difference. That jump especially helped my DP as well as mood, motivation, and cognitive abilities. The thing with Wellbutrin, at least for me, is that you have to be able to tolerate the side effects. It can make people jittery, anxious, and nervous. If that is so, it's probably going to make your DP worse. I couldn't tolerate those high doses without a benzo like Klonopin. However, I am able to tolerate 300mg of XL when taken with Remeron at bedtime. Remeron is great for sleep.

One more thing, I've recently accepted the fact that drinking too much really defeats Wellbutrin, probably more so that any other AD I've been on. The sense of pleasure from drinking comes from the release of dopamine, which, along with norepinephrine, are the primary neurotransmitters that wellbutrin is working on.

As for SSRIs, I never found them very useful except at low doses. Even then, the difference was slight. At high doses they make me more depressed, DPed, and makes my panic disorder worse. I've taken Celexa and Zoloft and I didn't notice much difference. I asked my doctor and he said if you don't respond to one SSRI, there's a good chance you won't respond to another. He says there are exceptions, though. But, a lot of times the side effects of one SSRI are a depressive factor, and a lot of people's mood improves just being on another SSRI with less side effects. With DP, though, I think people are a lot more worried about getting rid of the DP rather than worrying about side effects. Just my opinion.

Actually, I just remembered you said you weren't depressed or anxious and hadn't tried an SSRI, so ignore what I just wrote about SSRIs. This might seem to be a weird suggestion, but you might want to ask your doctor about Provigil, a drug for narcolepsy which is also used for depressives who oversleep and are fatigued. I have taken it in the past and it works really well for attention and cognition, and found it to work much better than Adderral or Ritalin. Unfortunately for someone with panic disorder like myself, insomnia and anxiety are some of it's main side effects, so taking it after a while just wore me down. I would reccommend you try an SSRI or another AD before making that jump.


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## dalailama15 (Aug 13, 2004)

Gimpy,

150 mg, two times a day, now for over a year.

At first It seemed to make a big difference, and I did quit smoking and begin other positive changes in behavior. But this seems to have worn off, and the 300 mg, now for quite a long time, feels as if I could just as well be swollowing M&Ms

(Interestingly, the XL, when I took it (150 then 300) seemed to be so different ( I found myself pacing and weeping) that I really wondered if they had putzed around with the chemistry just to compete with the just released generic version. I was, however, at this time,going through some real stress (possible incarceration) so this probably was the difference.

I am now taking the same 300 mg along with 300 mg of lamotragine, because of the research Jordon started this thread with, and that Uni-girl also spoke of. I am well into this trial and the only effects seem to be (slightly) negative.

The formula calls for lamotragene (which I now know I can easily tolerate--no fatal rash or weird behavior) plus, _specifically_, an SSRI. Your experience, as well as everybody else's, makes me a little more confident in making the lamotrigine/SSRI combo the new (and perhaps last) plan. Also, I feel I need to loose the Wellbutrin, just to see what it may or may not be doing.

What is left after this is maybe a tryciclic (which will pretty much finish off the ADs --with the exceptoon of MAOIs) or something a little exotic, like Pfovigil (whigh I had never heard of and now, certainly, will look at) or one of the more specifically dopamine-related drugs. And after that, I will probably give up on psychopharmacology all together, for fear that I am just making things worse.

Thanks for the advice and imput. As always, you sound really knowledgable about this stuff.

.


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## gimpy34 (Aug 10, 2004)

You're lucky that you don't really have depression or an anxiety disorder because that opens up your options. I'd go with the SSRI, or possible effexor (it's kind of like a mix of SSRI and wellbutrin to some extent) first like you're planning. Lamictal, with me, made my DP a little worse, not much, but it helped stop intrusive thoughts, like my mind moving a million miles per hour after a binge. What did you start first, the lamictal or wellbutrin?

If I were a psychiatrist, I wouldn't prescribe you a tricyclic. They're not really the cleanest drugs, they are notorious for bad side effects, one of which is clouding one's cognitive abilities. I started with a tiny dose of nortryptiline (1/10 the target dose) and found it unbearable. I didn't really have any non-psychiatric side effects, but it made me so confused and stupid, and made my DP much worse. That's just me, though. I think DP and cognitive abilities have a direct relationship. So, it makes sense for someone without panic disorder to try something like Provigil or Strattera (ADD drug). I know a few people on this board have had great success with it.


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## dalailama15 (Aug 13, 2004)

g, on anxiety disorders

When this first started for me, the main and most debilitating symptoms must have been anxiety attacks (although I didn't call them that)--basically pounding heart, shaky hands and voice, and the humiliation that this was obvious, and I couldn't control it. This would occur in any even innocuous kind of performance (like reading a paragraph in some class), let alone the kind of high profile performing I had been doing (beginning to play my horn like Harry James). Then sometimes even social situations began to seem like performances .as well, and could trigger the same physiological responses. .

I just wanted to tell you that with time most of this has just faded. That I think, at least from my experience, a kind of spontaneous remission is possible -- with time and some behavioral desensitization. I don't know much about this, and don't presume to, but this seemed to be perhaps a positive message.

And to answer. First the Wellbutrin, then more recently (3 months now) the lamictal. And it seems to have increased my DP, a little, as well.


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## university girl (Aug 11, 2004)

dalailama15 said:


> > not sure how it could induce a permanent change in neurobiology though
> 
> 
> My pet hypothesis is something like:


Interesting Dalailama. Thanks for your hypothesis. As for myself, my THC-induced neurochemical changes seem to be distinct from yours as I do not experience "emotional deadness, no sense of a continuous memory"... I do experience problems with integration of external stimuli, namely perceptual and auditory. Do you experience such problems? Oh, and by the way, you are doing well in understanding biochemistry despite your claim of a weak understanding of "even basic biology".  Since you seem to be just as keen on developing hypotheses as myself, can you develop an possible explanation as to why within weeks of constant DP/DR setting in I began to develop these peculiar more physical symptoms (ie. intense constant muscle tension and spasms at base of my skull, headaches, etc.)? ANYONE?

uni-girl


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## dalailama15 (Aug 13, 2004)

Uni-girl. Of course I'm just guessing, but all this stuff seems to involve the amygdala??a set of subcortical nuclei that is important for perceiving in others and having in oneself emotional or affective behaviors and feelings ?

Just googling stuff on the amygdala returns some fascinating and relevant stuff.

Regarding muscle tension there is this:



> Many gestures reflect the amygdala's turmoil. In an anxious meeting, e.g., we may unconsciously flex our arms, lean away, or angle away from colleagues who upset us. Lip, neck, and shoulder muscles may tense as the amygdala activates brain-stem circuits designed to produce protective facial expressions


Also, the amygdala sorts and integrates external stimuli:



> Electrical recordings have shown that the amygdala is responsive to a variety of sensory stimuli - visual, auditory, tactile, olfactory, and gustatory - and its connections allow it to monitor events in the environment - external stimuli - and control neural circuits in the hypothalamus





> [Regarding the] detection and evaluation of "salience" of stimuli and situation. . . key neural structures are LIMBIC SYSTEM (especially n. accumbens of basal ganglia and amygdala


The amygdala has direct two way connections to the hippocampus and to the hypothalamus 
The hippocampus is involved in long term memory and in connecting emotional information to biographical information, and some disruption here could easily cause my types strange symptoms, and DP symptoms in general.

The hypothalamus is, as I understand it, kind of a thermostat, turning on and off autonomic responses like pain, and some disruption here could easily cause more physical symptoms.

The hypothalamus is also strongly implicated in kinds of headaches:



> The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals. Malfunction of this area of the brain may give rise to cluster headaches


http://health.allrefer.com/health/cluster-headaches-hypothalamus.html

13,000 other google hits on hypothalmus and headache.

Someone said, in the context of multiple causes for similar symptoms, that perhaps ?all roads lead to Rome? (I think dreamer). Rome very well may be the amygdala.


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## university girl (Aug 11, 2004)

Dalailama,

Wow! I don't think any practioner has thought about my symptoms and tried to piece the puzzle together as much as you have. I sincerely thank you.  It is great having someone who is able to suggest such things and who I feel like is on my side. I really do hope a DP get-together comes together as I would really like to meet some of you guys.

I have to re-read and think over what you wrote and then I will respond.

uni-girl


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## DutchMark (Aug 10, 2004)

c'mon do you guys realy think there can be a permanent neurological change in the brain when you have THC induced DP/DR?
And uni-girl when you quited paxil, dit your DP/DR returned?


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## university girl (Aug 11, 2004)

DutchMark said:


> c'mon do you guys realy think there can be a permanent neurological change in the brain when you have THC induced DP/DR?
> And uni-girl when you quited paxil, dit your DP/DR returned?


DutchMark,

Yes, I do believe THC can induce a long-lasting change in brain chemistry. THC was definately the trigger of my DP/DR. What is your theory, DutchMark (a serious question)?

This is taken from Daphne Simeon's paper Depersonalisation Disorder from CNS Drugs, 2004:

"... chemical triggers of a specific nature can initiate long-standing depersonalisation disorder..."

Presented in the paper were two theories as to how such a phenomenon could exist:

1) In those already susceptible to DP, the experience the user has with the drug is in itself traumatic, therefore leading to DP
2) "drugs act as highly specific triggers that dysregulate already vulnerable neurochemical systems that may underlie the neurobiology of depersonalisation disorder"

 This suggests a 'permanent' change in neurobiology (to me atleast).

Oh, and I have not quit paxil. Not sure where you got that from. I've been on it for 3.5 yrs now. Perhaps you are referring to a time where I tried to change to Celexa? And yes, at this time the DP/DR was horrific.

-uni-girl


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## university girl (Aug 11, 2004)

Dalailama,

I have started a new thread on THC-induced DP/DR in "Depersonalization / Derealization Medical Explorations" so we can talk about it there instead of here.

-university girl


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