Serotonin

Specific Illnesses & Conditions VM/MAV
1

Is there an article that explains the role serotonin plays in chronic migraine?

The kid was terribly difficult to medicate for anxiety. Anything that increased norepinephrine (like the tricyclics) caused an enormous uptick in his sensory hypersensitivity, and with it increased irritability. (He’s the kind of kid that found blue jeans hard to wear because they felt like sandpaper against his skin.) SSRIs reduced his anxiety, but caused a variety of difficulties, depending on which one we were trying. Abilify was helpful, but induced tardive dyskinesia. (I don’t know what neurochemicals Abilify works on.) He ended up on lamotrigine, which has been wonderful. I know lamotrigine reduces glutamate levels in the brain, and I know it’s sometimes used on its own for migraine prophylaxis. And glutamate is involved in migraine, isn’t it?

Anyway, if you can point me to something that is understandable by someone who is not a neuroscientist that explains what role serotonin plays in chronic migraine, I’d be grateful. And if it talked about glutamate, too, that would be interesting as well. When I’ve poked around online, I’ve mostly found stuff that I wasn’t sure was trustworthy, or else stuff published in research journals that I couldn’t understand as I don’t have an advanced degree in chemistry or mathematics.

Thanks!
Mamabear

2

HI Mamabear,
Abilify hits dopamine and Serotonin…I have a prescription my doctor wants me to try, but I"m reticent…it has a really long half life as well, so I’m not sure. However, Lamotrigine (Lamictal) is one that I have heard a lot of good things about. I think I would be more open to that than the Abilify…did you do a slow titration? I know there is a rash associated with it if you titrate up too fast, so hopefully you don’t have that problem. I thought I read on another post that you had the kid on Propralonol? I might be mistaken…
Anyway…good luck with everything and I"m glad things are better.
:slight_smile:
Kelley

3

Hi Mamabear –

Are you interested in having a look at this? It looks hard core but I can grab it and translate if you like:


J Headache Pain. 2008 Oct;9(5):267-76

Abstract
The 5-hydroxytryptamine (5-HT) has been implicated in migraine pathophysiology for the past 50 years. A low central 5-HT disposition associated with an increase in 5-HT release during attack is the most convincing change of 5-HT metabolism implicated in migraine. Peripheral studies on plasma/platelet have not generally shown low 5-HT levels. Studies on 5-HT reactivity showed hypersensitivity, also expressed as reduced tachyphylaxis (habituation), which successively was evidenced as the most characteristic marker of an altered sensory neurotransmission. Even the gender and seasonal variations of 5-HT parameters seem to agree with a low 5-HT turnover with receptoral hypersensitivity. The interpretation of the effects of some serotonergic drugs and recent neuroimaging studies give major evidence for this cascade of events. Although the exact mechanism that links abnormal 5-HT neurotransmission to the manifestation of head pain has yet to be fully understood, a deficit on 5-HT descending pain inhibitory system is still probably today the most implicated in migraine pathophysiology. This short review focuses and discusses the alteration of peripheral and central 5-HT parameters in migraine patients.

4

Scott, yes, if you could help me walk through it, I’d love to read that! I can tell from the abstract that it’s over my head, but I think not so far over my head that I couldn’t get it if I had some help.

Kelley, the kid’s psychiatrist follows the “start low, go slow” philosophy with all meds, and especially for lamotrigine. She titrated that up really, really slowly. And, yes, the reason for the go-slow with lamotrigine is Stevens-Johnson Syndrome, otherwise known as “The Rash.” Only it’s not just a rash – it can kill you. (I know some people here have been scared about taking psych meds – take any fear that you feel and multiply it a zillion times, and that’s how it feels to start your kid on a medication like that!) But the rash is rare, and so far, there’s not been any problem.

Yes, he’s on propranolol, too. Since lamotrigine also acts as a migraine suppressant, one option for the neuro would have been to increase his dose on that, rather than starting a new medication. But, first, the neuro didn’t want to muck with a drug a different doctor had prescribed for something else. And besides, the risks from lamotrigine are pretty much all when you change the dose. So she added propranolol. And it’s worked, so I think it was a good call. (Does propranolol affect neurotransmitters? Or does it help prevent migraine some other way?)

The psychiatrist said that propranolol and lamotrigine play well together. So both docs are happy with his meds now, and the meds are working. But when we’re giving the kid all these kinds of high-powered meds, I feel like I have the responsibility of understanding what they do, and how they work. I need to understand what can go wrong, and why, too. And I was an English major – wrapping my mind around a lot of this stuff is hard work!

When the kid was on Abilify, it was the first time in his life that he wasn’t totally disabled by his anxiety. It was amazing. When the tardive dyskinesia started, he didn’t want to discontinue the medication. He was willing to tolerate a small amount of involuntary movement, if that was the cost of turning down the anxiety. The psychiatrist watched it closely, and started him on Vitamin E (which she said is neuroprotective), but when it started to get worse, she and the kid agreed that he needed to discontinue.

We discontinued that fast, and ramped up the lamotrigine slowly. That was a rough time. But not nearly as rough as this fall/winter, with the migraine.

Mamabear

5

Mamabear,
the anxiety was helped with the Abilify? What dose was he on? My doctor wants me to try it and the TD is scary to me!! I have to say anxiety is the worst feeling, maybe on par with bad vertigo…neither should have to be endured!!
Kelley

6

Kelley, I honestly don’t remember what the dose was. But it turned his anxiety way, way down. It’s not without risks; no drug is. Whether the benefit is enough to make the risk worth taking is going to depend on so many things.

In the kid’s case, it was definitely worth the risk. If you were to start on Abilify (or any other drug that carries a risk of TD), it’s easy enough to stick out your tongue at yourself in a mirror once a week or so, and look for any movement on the surface of your tongue. That’s how TD starts. If you don’t see any movement, you don’t have to worry about it. And if you see it, you can immediately start taking Vitamin E, and talk to your doctor about discontinuing.

But I don’t think TD is terribly common. The kid just has a tendency to have every side effect listed for a drug, and some that no one has thought of yet.

Mamabear

7

Why Do you keep saying ‘The kid’ is this your son your reffering to ? Maybe its where Im from but that’s a strange term to use ?

8

Hi, Blondie. Yes, “the kid” is my 15-year-old son. When I logged in here the first time, I felt like I needed to be entirely anonymous, for myself and for him, because it’s his personal medical information I’m talking about. If it were me, I’d be using my own name. But if one of his friends googles him, I don’t want my comments about what meds he’s on, or what his diagnoses are, to come up. It’s up to him to decide where and how to share that kind of information.

So I called him “the kid.” Around here, “kid” is an informal term for a young person. Is it something different where you are?

Mamabear

9

That’s fair enough Mamabear. I can imagine as a 15 yo, the last thing he would want is for this stuff to be known by his peers. I can’t imagine having to have dealt with a migraine drama like this in those years of life. I’m just glad he’s sorted out now and pretty much back to normal.

S

ps. Paper coming soon. Been too busy at work again and fighting some very bad non-stop headaches that won’t let up.

10

Yeah I know what you mean you need to stay discreet for your son for his privacy. Its justI wasn’t sure if it was your sure as you kept saying ‘the kid’ which seemed more Impersonal. Im from England we do say it just not in the same way you say it LOL Hope your son is feeling better x

11

— Begin quote from “scott”

Paper coming soon. Been too busy at work again and fighting some very bad non-stop headaches that won’t let up.

— End quote

We had a little too much going on at our house the last couple of weeks, too. I hope your headache is better – and that you’re not affected by the cyclone.

Mamabear

12

Mamabear – sorry for the delay. I’ve added the full paper in there now for you to see. I still haven’t had a chance to read it though. Have a go at it and let me know if it’s readable or just all Greek.

S :slight_smile:

13

Thanks, Scott. This will be my lunch-hour reading today. I’ll let you know if I can make heads or tails of it!

Mamabear

14

Scott, this article is right at the edge of my ability to understand – which means, of course, that I’m not entirely sure whether I understand it or not! I could have things entirely wrong.

To start with, this looks like a meta-analysis – they didn’t do any new research, but just looked at all the existing research about serotonin and migraine to see what it said. I think they were trying to figure out two things. First, whether migraine is caused by having too little serotonin. And second, whether people with migraine are more sensitive to “natural or experimental alterations of the serotonergic system” – that is, whether people with migraine are more likely to feel bad if you muck with their serotonin levels.

The first appears not to be true. SSRIs and serotonin agonists aren’t helpful for migraine, anyway. And the research that should have shown differences between people with migraine and controls really didn’t.

The second, though, may well be true. Even though a generally low serotonin level doesn’t seem to be related to migraine, having your serotonin level crash (as happens “in the perimenstrual period, in the relaxation period after prolonged stress …, after acute stress …, or … after alcohol intake” or after taking certain drugs like mCPP and ecstasy) can trigger migraine. So anything that changes your serotonin levels is potentially problematic for migraineurs.

Am I close?

If so, I’ve got some questions.

I’m not sure what they mean by “turnover” when they’re talking about serotonin turnover (and turnover of other neurotransmitters). That seems to be important, especially because serotonin turnover varies seasonally, and dopamine and norepinephrine turnover don’t.

Is there any correlation, positive or negative, between SAD and migraine? Is light therapy ever used for migraine? So many of the drugs that are used for migraine are also used for bipolar – are these drugs stabilizing serotonin levels? Is that the way they work for both diseases? Is there any correlation between bipolar and migraine?

And, at the end, the article talkes about Sicuteri’s theory about migraine being an alteration in pain transmission and concludes by saying that “a deficit of central serotonergic antinociceptive system.” What does that have to do with the rest of the article? And how does it explain migraine that doesn’t have headache associated with it?

Thanks!
Mamabear

15

Hey Mamabear –

It sounds like you’ve ploughed through the article very well and got a lot out of it. I’m interviewing flat mates today but should be able to have a read either tonight or Sunday.

At first glance, a low turnover rate of serotonin to me has to do with the rate of production and breakdown. Brain serotonin and dopamine metabolism (5-HIAA/HVA) mutually regulate each other (5-hydroxyindoleacetic acid is a product of serotonin breakdown). Therefore, either a low 5-HIAA or HVA concentration can, under certain circumstances, be indicative of reduced central nervous system (CNS) serotonergic activity. Serotonin is synthesised from L-tryptophan (amino acid) and by taking it orally, we can upregulate serotonin production. We can also upregulate it with 5HTP which is an intermediate between tryptophan and serotonin. Both tryptophan and 5HTP can cross the blood-brain barrier. If we took serotonin alone, it would only affect the digestive system and cannot enter the brain.

http://upload.wikimedia.org/wikipedia/commons/1/1c/Serotonin_biosynthesis.svg

Interestingly, SSRIs work by keeping serotonin doing it’s thing longer in the synaptic space (cleft) where it can keep on binding with its receptor and make us feel better. Have a look at the diagram below. I am quite certain that I have a serotonin metabolism problem or that it easily disrupted causing me all the pain and hassles. I read an interesting article hypothesising that amines, sulphites, and nitrites are not taken care of properly in the migraineur’s body and they screw up serotonin somehow which then kicks off the migraine.

The yellow bit is the axon terminal where you see the little round vesicles, the black is the synaptic cleft, and the green is called the dendrite where the receptors are.

http://upload.wikimedia.org/wikipedia/commons/1/1b/Synapse_Illustration_unlabeled.svg

Scott

16

— Begin quote from “scott”

Interestingly, SSRIs work by keeping serotonin doing it’s thing longer in the synaptic space (cleft) where it can keep on binding with its receptor and make us feel better. Have a look at the diagram below. I am quite certain that I have a serotonin metabolism problem or that it easily disrupted causing me all the pain and hassles.

— End quote

That makes sense. If the problem isn’t a low level of serotonin, but a level that fluctuates, then having a serotonin system that is easily disrupted would wreak all sorts of havoc.

But why don’t SSRIs stabilize the level of serotonin? It seems like they should.

Anyway, I’m looking forward to your further comments on the article. Thanks!

Mamabear

17

Hi
Just wanted to poke my nose into this thread specifically about Abilify and antipsychotic meds and TD. As a Speech Therapist I’ve had quite a few patients referred to me with TD and it can be permanent, even after drug withdrawal. It’s usually after being on them a long time but I did have one lady who was on it for very short time with severe TD.
Don’t want to frighten anyone but I just think we should all be aware of potential adverse effects.

D-I

18

Dizzy Izzy,
Do you know how high of a dose she was on? That is a big fear…that would SUCK!! I have enough things that suck with mav than to add that stuff in the mix!
Kelley

19

Sorry whats TD?

20

Tardive dyskenesia. A neurological movement disorder a bit like Parkinsons Disease, causing involuntary writhing of muscles. Can affect limbs and/or facial muscles (hence speech). Not nice.