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Migraine Symptom Predicts Response to Imitrex

When we launched CureTogether in 2008, we believed that if we could simply ask thousands of people about the details of their experience with different health conditions; gather their responses in a structured, quantitative way; and apply the right algorithms to that data; important discoveries would emerge that could reduce needless suffering.

Considering how valuable good health is to all of us, and how much time and money is spent each year to maintain it, it seems incredibly wasteful for millions of people to leave, locked in their heads, detailed knowledge about their experience with conditions, symptoms and treatments.

Migraine was one of the first conditions added to CureTogether, and one for which we’ve gathered the most data. One of the most popular and highest rated treatments is Imitrex (Sumatriptan). Most people who try Imitrex report an improvement in their symptoms, but a significant 11% report feeling “much worse” after taking it.

There are two good reasons why someone with Migraine would want to know how their risk of having a negative reaction compares to the average: 1) Migraines are hard enough to endure on their own – you don’t want a negative reaction to a treatment to make it even harder and 2) Imitrex is expensive – costing as much as $30 per tablet!

We were interested in whether differences in symptoms might account for some people reacting negatively to a treatment that otherwise helped so many people feel better. So, starting with a subset of 38 Migraine symptoms that at least 100 members had reported having, and at least 100 members had reported not having, and for which all members had also provided effectiveness ratings for Imitrex, we segmented members into two groups:

Group A = those who reported having the symptom
Group B = those who reported not having the symptom

We then further segmented these members according to how they rated Imitrex:
- major improvement
- moderate improvement
- no effect or uncertain
- made it slightly worse
- made it much worse

To determine which symptoms had the greatest influence on negative ratings of Imitrex, we calculated, for each row, the negative response ratio (NRR) as follows:

NRR = p(MW|Y) / p(MW|N)

where:
- p(MW|Y) = the fraction of members having the symptom who rated Imitrex “much worse”
- p(MW|N) = the fraction of members NOT having the symptom who rated Imitrex “much worse”

After ranking the symptoms from highest to lowest NRR, ”Vertigo / Dizziness” came out on top, with an NRR of 4.2x.

Among CureTogether members with Migraine, the overall probability of reporting a “much worse” response to Imitrex is 11%. Of those who reported not having “Vertigo / Dizziness”, only 4.0% reported a “much worse” response to Imitrex. Of those who reported having “Vertigo / Dizziness”, 17% reported a “much worse” response. Thus, members who reported “Vertigo / Dizziness” were 4.2x more likely to report a “much worse” response.

To test for significance, we needed to determine the probability that a 4.2x (or more extreme) NRR could be generated by chance, rather than as a result of a genuine influence. Our null hypothesis was that whether someone had, or did not have, Vertigo / Dizziness had no effect on Imitrex ratings. We generated 1 million fake datasets by randomly permuting the User ID’s for Imitrex ratings, pairing members of Groups A and B with real, but random Imitrex ratings, rather than their own, and measuring the NRR each time.

The frequency of a 4.2x NRR within the fake datasets would indicate the probability that the such a value could be generated by chance, assuming the null hypothesis were true. We ran the analysis and plotted the sampling distribution of 1 million NRRs as a histogram:

An NRR of 4.2x would be generated with a probability of 2.44e-4 – i.e. only one in ~4,000 times would we see such a result by chance if the null hypothesis were true. Usually, scientists consider a p-value of < 0.05 to be significant, so this is a very significant result, even if you factor in the fact that we only discovered the 4.2x result after sorting 38 symptoms.

But dizziness is a known side-effect of Imitrex. How do we know that those CureTogether members who tried Imitrex were not just more likely to report dizziness as a side-effect, rather than as a symptom prior to trying Imitrex? How do we know that Vertigo / Dizziness actually predicts response to Imitrex? Well, if it were a side-effect, then we would expect members who tried Imitrex to be more likely to report significantly more Vertigo/Dizziness. Here’s what the data says:

While 76% of those who tried Imitrex (224/293) reported Vertigo / Dizziness, 72% of those who did NOT try Imitrex (246/340) also reported it. There is only a 5% difference between these two groups, in contrast to the 4.2x difference above. While this may seem counterintuitive, keep in mind that the probability of reporting a symptom, given that you have tried a treatment is not the same thing as the probability of giving a treatment a negative rating, given that you’ve had the symptom. p(s|t) != p(mw|s).

Now, there is one caveat – we cannot assume that these results apply to all Migraine sufferers. Although we see promising early indications that CureTogether members are representative of the general population, we are not ready to make that claim conclusively.

Thus, we have demonstrated that, among CureTogether members with Migraine at least, having Vertigo / Dizziness as a symptom increases the chance of reporting a “much worse” response to Imitrex by 4.2x, from 4.0% to 17%.

We are enthusiastic to have this result confirm our initial belief in the power of CureTogether’s approach to health research. We also believe this is the first of many predictive discoveries across the 500+ conditions for which we continue to gather data.

Thank you to our members who took the time to participate in our surveys. And special thanks to Dr. Will Dampier, Research Assistant Professor at Drexel University School of Biomedical Engineering and Health Systems, for his help with the statistical analysis.


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24 Responses to “Migraine Symptom Predicts Response to Imitrex”

  1. Will Dampier Says:

    Glad to help … I’m one of those data-points of migraine suffers who has vertigo and reacts poorly to Imitrex. I’m glad to see data showing that I’m not just crazy ;)

  2. [...] This post was mentioned on Twitter by Chris Hogg, Gary Wolf. Gary Wolf said: Beautiful case of using self-tracking data to predict medication effects, from @CureTogether. http://bit.ly/hoIdH2 #quantifiedself [...]

  3. Jean Hoffman Says:

    I had migraines from age 13 to age 61 when it was cured forever 15 years ago when I had chemotherapy for breast cancer. Before that, I found biofeedback the best therapy since there were no pain killers that worked for me – before Imitrex was on the market.

  4. Sumatriptan or Imitrex by injection is the only drug that has ever worked for me. However, I buy the vials and syringes and find that I only need about half or less of the auto-injection amount. I do get a rush of increased pain for about 15 minutes or so after injection, but it gradually dissipates, along with the migraine. Sometimes I have to repeat the injection. I get migraines several times a week. I’ve had them for well over 50 years.

  5. Glad to have these results to help me decide the medication I select for my migraines.

  6. Melanie Symonds Says:

    I’ve long been frustrated by doctors who don’t really listen to what I’m saying about my symptoms, so I’m very glad to see this type of research being carried out and already finding significant results in the data.

    I’m lucky to be a migraineur for whom the Triptan class of abortive medications do work, but I’m eager for the day when a truly effective preventive, targeted solely for migraine disease, is developed.

  7. Thanks for listening to us…imitrex does nothing for me. A shot also does nothing. I get tired of being treated like an addict just because I need pain medicine. Believe me… if I didn’t need relief just to function normally…I wouldn’t be taking this much medicine
    I just got fired for missing too much work due to my pain level being too high to drive….I am happy I am not the only one. I just wish doctors got this information and applied it on a somewhat regular basis.

  8. Another thing that worked for me was caffergot suppositories. No one sold them, but a compounding pharmacy made them for me. They did make me thow up, which was unpleasant, but they were the best thing at the time. This was before Imitrex. They might be something to think about for people for whom sumatriptan doesn’t work.

  9. Stormlaughter Says:

    Well, chalk me up in the “vertigo/Imitrex makes me far worse” group.

    One thing I want to mention: vertigo is vastly different from dizziness.

    I’m retired on disability pension from Meniere’s Syndrome. One of the four consistent symptoms of Meniere’s is rotational vertigo – either the room feels like it’s spinning or the person feels like he or she is spinning and the room is still.

    Dizziness is a description of lightheadedness which has no sensation of movement associated with it.

    Vertigo and dizziness have unrelated root causes and different meanings to a doctor. Dizziness is a symptom of drug allergic reaction and vertigo is not, for example.

    Separating vertigo from dizziness might give interesting results if anyone has time to do it. :)

  10. Imitrex didn’t work for me. I didn’t use for long, and that was some years back so I don’t remember if vertigo was a problem. Cafergo suppositories worked well, but those were taken off the market. The only thing that really works for me now is Zomig.

  11. I had one shot of Imitrex – that was enough. My skin started burning and itching within minutes. My heart was pounding so hard I thought people in the lobby could hear it, and to top it off, my headache got immediately worse. It was not a good experience for me.

  12. Daniel, Superb article! Most of all, excellent job breaking everything down and thoroughly explaining what the statistics meant. It really helps give a better perspective.

    Viewers: As everyone knows, everyone reacts to different meds differently. And considering they don’t really understand exactly how it works, you never quite know what the results will be.

  13. Hi,

    thanks for the whole project, I really like the spirit, and I think this can become a very important source for knowledge about health!

    I also like the permutation analysis. However, IMHO it might have been important to report sensitivity and specificity (http://en.wikipedia.org/wiki/Sensitivity_and_specificity) so that the diagnostic utility of “vertigo and dizziness” could be estimated. Even though the risk of “much worse” is four times higher in patients with dizziness, the large majority are not much worse. So depending on how the positive effects are distributed (how were they?), I might still be a good idea to try Imitrex.
    A recent review of trials into response to different triptanes also finds that the response to a particular triptane cannot be predicted based on the response to previous triptanes (Dahlöf, 2006: http://www.ncbi.nlm.nih.gov/pubmed/16426262).

    Sorry for being picky, but I really take this seriously.

  14. What would be great is if they could look into what medicine works best for those with dizziness. I for one stopped taking any medicine for my migraines about four years ago because I had a negative reaction to Imitrex (my skin would feel like it was burning and my migraine would get even worse) and was tired of trying all kinds of different medication to help with my migraines, none of which ever worked.

  15. Interesting study. It is unfortunate that the study was done with the oldest of Triptan therapies on the market. I find Zomig 5mg nasal inhaler much more helpful. Also, Maxalt 10mg tabs are pretty good. I have had migraines severely and almost daily for three years now. I lost my Career of 23 years as a result. This of course due to missing so much work. I wish that research would put more money into both abortive therapies, as well as prevetative therapies. Now losing multiple days to a migrain for so long feels like one’s life has been taken from them. And may I add that being on strong pain medicine is not fun, nor desireable. It does nothing to make a life bettter. It ruins a life, a long with the migraines. But without it, I would be in the emergency room constantly. Good work, please keep working on finding more answers for those of us mirgaineurs.

  16. Keith and Mairin, great comments! YES, we will be doing more research on both abortive/preventative therapies, and treatments that work for migraines with dizziness. Thank you for your excellent feedback, and I wish you well.
    Alexandra Carmichael, CureTogether co-founder

  17. Hi!

    I really enjoyed this post. It gave me a better perspective on how to deal with migraines. I also used imitrex, but since I also have rosacea this didn’t help me very much. My headache was less, but my face was red like a tomato, and very, very itchy. So this was no alternative for me.

    I read a lot on both rosacea and migraines and discovered that a lot of people see a connection between the two. Do you feel the same ’bout this?

    I found that an alkaline diet helps me the most, and identifying triggers is also important. Do you have any suggestions about this?

    Thanks for the really good work!

  18. [...] data aggregations revealed that people who experienced vertigo in conjunction with migraines were four times as likely to have painful negative reactions when using the migraine drug Imitrex as those who did not have [...]

  19. [...] data aggregations revealed that people who experienced vertigo in conjunction with migraines were four times as likely to have painful negative reactions when using the migraine drug Imitrex as those who did not have [...]

  20. [...] of information aggregations suggested that people who gifted vertigo in and with migraines were four times as expected to have unpleasant disastrous reactions when regulating a migraine drug Imitrex as those who did not have [...]

  21. [...] data aggregations revealed that people who experienced vertigo in conjunction with migraines were four times as likely to have painful negative reactions when using the migraine drug Imitrex as those who did not have [...]

  22. I have had migraines without aura since age 13 or so. Imitrex has been a miracle drug for me. About 10 years ago I started getting migraines without pain, which have all the symptoms of a migraine including dizziness, but with no head pain. I thought these were a gastro-intestinal problem, but a brilliant gastroenterologist diagnosed them as migraines. Imitrex worked fine for them as well, and I seem to have stopped getting them, although my regular migraines continue. As has been said above, although this is extremely useful research, and I love this site in general, it’s still worth giving Imitrex a try for an individual.

  23. Imitrex and I have had a love/hate relationship. Coincidentally, I wrote about my experience, my interaction with Imetrix, migraines, etc., in a post on my (relatively) new blog, http://laughingfrommysickbed.blogspot.com/2012/03/laughing-from-my-sickbed-about-needles.html
    I’m not sure about the protocol when it comes to identifying oneself and further, disclosuring oneself as being a blogger on “comments,” since I’m new to the blogging world and am pretty pathetically non-knowledgeable about the computer and the Internet, so I apologize ahead of time if I’ve stepped over any lines.  But I’ve had CFIDS/ME/fibro for 37 years, vertigo for 15 years, though migraines since childhood.  

    I wish I’d known more about Imetrix way back when (shot form) but am really thrilled to see this sort of information coming out to help others, and indeed all of those who suffer pain, because, obviously, with each new piece of a possible puzzle piece, we’re that much closer to understanding all this torment endured by way too many.  

    I also suffer from “body migraines,” a term given to me after I was finally diagnosed in the late 80′s with CFIDS, etc.  Frova has been extremely helpful and when I see that I am getting constant migraines (seemingly without end), and that I’m constantly taking pain meds that no longer touch any of my pain at all, that’s when I have to realize what’s going on, kick myself and force myself to go back to eating the “right” foods (for me!) and stop eating those foods that contribute to my migraines. I’m not always successful with the food restrictions, but they along with Frova have been a pretty decent combo recently…knock on wood!

  24. [...] data aggregations revealed that people who experienced vertigo in conjunction with migraines were four times as likely to have painful negative reactions when using the migraine drug Imitrex as those who did not have [...]

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