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Will Botox Work For You? New Study May Provide a Clue

Ever since 2010, when the FDA approved Botox for the treatment of chronic migraine, migraineurs and/or our doctors have been eager to try it. (My neurologist, for instance, brings it up at every appointment, though at an $180 copay per treatment I’ve so far balked at the idea.) Many patients, including numerous readers and several of our contributors have experienced significant relief from the injections, some going from nearly daily migraines to as few as one every other week or so. Other patients, however, haven’t been so lucky.

For some migraineurs, Botox seems to do little or nothing. For a select few, it can even make matters worse by aggravating the neck muscles and/or triggering additional head pain. So, what’s a migraineur to do? Try or not try?

A new study recently published in the journal Headache may offer a new way to decide.1

Researchers in Spain looked at the correlation between Botox response and two peptides that can be found in the blood: calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). They recruited 81 adult patients with chronic migraine and 33 matched patients with no headache history. They then tested the CGRP and VIP levels of the participants prior to treating with Botox. They also measured the participants’ responses over the course of treatment.

The results of the study were striking, particularly when looking at CGRP levels.

Participants whose CGRP levels were above 72 pg/ml were 28 times more likely to respond positively to Botox treatment than participants whose CGRP levels were below 72 pg/ml. (Positive response, for the purposes of the study, was defined as an improvement of at least 33% in both the frequency of attacks and in a subjective analysis of a visual scale of 0-100.)

Though this certainly shows a correlation between CGRP levels and Botox responsiveness in chronic migraineurs in this study, readers should note it was a very small study. Therefore, additional researchers conducting their own studies will need to repeat and confirm the results before doctors will start using CGRP levels to determine whether to give a patient Botox. (If the results are confirmed, we’ll also need to wait for the CGRP test to become more widely available. At this point in time, only research laboratories can do it.)

For now, migraineurs who want to have some idea of whether or not Botox will work for them specifically may want to check out the research on pain directionality and Botox response.2

The gist of the pain directionality research seems to be that migraineurs who experience ocular/eye-popping pain and/or crushing, vice-like, or “imploding” pain seem to do better on Botox than migraineurs who experience exploding pain (i.e. pain that feels as though it is building up inside the head and then pushing out). Some migraineurs, however, may find it difficult to speak of their migraines in this way, and may therefore have little use for such a “test.” For these migraineurs (and I count myself among them), a blood test like the CGRP test may be particularly valuable.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Headache. 2014 Jun;54(6):987-95. doi: 10.1111/head.12372. Epub 2014 May 6. Available at:
  2. Arch Dermatol. 2010;146(2):159-163. doi:10.1001/archdermatol.2009.356. Available at:


  • Judy
    5 years ago

    Several years ago I had Botox when my migraines became chronic. My neck went into severe spasms causing me to have to leave work to put heat to alleviate the pain. My forehead felt such pressure like there was an elephant sitting on it the entire three months! I hated the feeling the entire three months that it lasted and swore I would never ever do it again!! However, it was successful in cutting down the number of migraines but that was not worth the pain I felt in my neck and the discomfort I felt in my head. I don’t know if it was how the Botox was administered but I would be so afraid to try again. I have increased my Topamax to 300mgs. ,Inderall to 80mgs, and for the most part my migraines are manageable…three times a week or so. I try and exercise most days when I can, walking and light yoga. It is only when I am curled up in bed for four days in a row that I begin to wonder whether I should ever try it again. I am fortunate that my insurance covers most of the cost…but it is very, very scary stuff ,

  • Paulaff
    5 years ago

    I tried Botox last fall, but got no relief. Then I changed neurologists & he recommended another treatment because sometimes it takes two rounds. So I did, in Jan. No help again.

    I guess I’m at the end of meds available for migraine prevention, so I don’t know what I’ll do next. Does anyone know of any drugs in other countries that are touting migraine prevention?


  • technopeasant
    5 years ago

    I have read this site for about a year now and my thoughts are these. Many of you guys are not much better than me. I started having symptoms I recognize as migraine now when I was in about the sixth grade but, I just read the comment, about the burning ears symptom and remember my mother thinking it was a strange complaint when I was in the second grade. Now that I have a diagnosis at 62 I recognize so many things in my life as related to migraine. I am an nearly lifelong migraine sufferer, well might as well say lifelong. I also remember those hot ears always being on the same side as the migraines.

    When I was in college at about 19 I had an attack that lasted over a year. My ears got so bad I had to have tubes installed like a kid. The ENT said I had so much fluid built up behind my eardrums and in the bone he knew of no other way to break the cycle of ear infections. Cortisone was new then and doctors didn’t have the experience with it they have now. He left me on it so long I almost died from the combination prednisone and antihistamine drug from adrenal cortex suppression. I was living in Nashville at that time and ask for a referral to Vanderbilt Allergy Clinic. I sought refuge there for “allergy problems” for about 10 years. I got really no better. One time the allergy doctor commented “your headaches sound like migraines sometimes?”. He continued on in his original thought with hardly a second spared. I am a man so migraines seemed out of place in his thoughts in those days, I guess. I suffer with hardly ever a migraine free day each month. When there are a few it is a monumentous occasion. I actually had such a two week period the first of June this year. But, Their back now!

    I remember my first really severe headache was when I was a Junior in high school. It hit me out of the blue walking down the sidewalk beside my school. I went home and went to bed. That headache went on for weeks until I had been to the local doctor three or four times. He treated with antibiotics, cortisone sprays. I finally went over to the bigger town next door and saw the ENT. He said Sinus infection. He washed them out, gave me another antibiotic and the headache got some better. It was an infection I believe now, but only because the migraine got so bad the swelling was in tolerable for my body. The earaches continued as did the sinus problems. I have an earache migraine now. Most of the time when I have a severe period of migraines they are accompanied by major depressive episodes. These have, along with migraines put me at the edge of suicide a number of times.

    About twelve years ago I had the worst of both. I had the worst depression episodes of my life. Along with it was one of the worst migraine episodes. I began to get the depression under control with anti-depressives but the headaches were murderous. I walked into the allergists office for a yearly visit. She looked at me and said you look like you don’t feel very well. I replied that I had a really bad sinus headache. To which she replied, “describe it to me.” To which I commenced with the best description I could do. She is a really good typist and listened looking me in the face and taking notes at the same time (she’s that good). She said “let me look” and took a quick look in my nose. Her immediate reply was, “You don’t have a sinus headache, you have a migraine”. She left the room and brought me back a tablet and a cup of water saying, “here take this.” We continued to talk for about twenty minutes. She then said “How’s your headache?” To which I said, “It’s gone!” She wrote out prescription for a triptan and made a referral to a neurologist. OH! if it were only that simple!!! At least now I know.

    If knowing only provided a solution. I am on about my tenth anti-seizure med and have tried all the support meds you can think of. Triptans work for about 10-15 hours then the pain and other symptoms are back in worse measure. I am now taking Vimpat it is the only anti-seizure med that has ever helped and it has to be on the edge of intolerable side effects to work. The others either made no difference or had such terrible side effects I couldn’t take them. Topamax nearly killed me. It caused severe appetite suppression by causing everything to have a unbearable metallic taste that carried over to drinks even water! I still have constant ringing in my right ear from it. I nearly went deaf and both ears were severely ringing and almost deaf from it. I got dehydrated and my kidneys got damaged. All the while the neurologist was saying I just “must have a virus.” I finally stopped taking it myself. I have seen five neurologists one who was a headache specialist. I lost my job. I am now disabled and the headaches go on.

    One final word I told my primary care 15 years or so ago that something must be causing the neurological problems I was having. Basically what seems to be my “final diagnosis” (however you make that plural) are chronic severe intractable cluster migraines, rheumatoid arthritis, major depression, diabetes (mainly brought on very early by constant treatment with prednisone)and severe degenerative disk disease brought on by the RA. If you carry the diabetes gene, cortisone can accelerate early manifestation of diabetes so be sure you are checked often if you take it. That’s my record of woe. It is too bad that medicine can’t diagnose these things early and prevent so much suffering by prevention. But unfortunately suffering is the necessity that brings on the diagnoses. I hope they do better in future years for our children’s sake.

  • technopeasant
    5 years ago

    PS: Sorry to be off subject. My first comment. I didn’t know there was a subject I was just posting.

    I have had nerve blocks which seem to help for a few days. But they use cortisone and it is not worth it for me considering the diabetes exacerbation.

  • cathyn
    5 years ago

    I have been getting migraines 3-5 times a week for almost two years, and after triptans stopped working, went the Botox route. Had first round in Jan. and I would say improvement was slim to none. However, I was happy that I had no side effects.
    Decided to go for second round in May. The dr. I’m seeing for the injections told me it takes 2-3 rounds to see improvement, and if there isn’t any at that point, it’s probably not going to work.
    This time he gave me a higher dosage on the left side (where I have symptoms), and within 24 hours I had one of the worst headaches (not migraine) I’ve ever had in my life, and the flu-like symptoms Katie Golden described. This lasted for 3-4 days and was almost as bad as migraines themselves.
    I did notice this time more days where migraines weren’t as severe. Mine are very very much weather triggered so it’s hard to say if it was Botox or just more stable weather. Will I go for round 3? I’m still deciding. I have a $150 co-pay, and not sure it’s worth it. I’m also afraid of the horrible side effects again. But, I’ve also seen a couple comments that round 3 offered improvement.

  • cathyn
    5 years ago

    Sorry BellaRobina, I have been out of town and am just seeing your comment now. I don’t think it was a direct result of where the injections were, as I had a general feeling my head would explode, and the injection sites didn’t bother me much. It was not a migraine (I get those on left side only), and I didn’t have nausea or brain fog,which I get with migraines – it was just a horrible headache, along with achiness and fatigue.
    I’m sorry you had the headache for two weeks, luckily mine was only four days, but that was more than enough. The more I read posts, the more I think there are just some of us who react poorly to treatments.

  • BellaRobina
    5 years ago

    2 years ago I went to a cosmetic surgeon (first mistake) to get botox for headaches. He gave me a very low dosage and put the shots on forehead and between the brows. By the time I got halfway home I was in agony. I had one of the worst headaches I have ever had and it lasted for 2 weeks. I don’t know if it was the doctor, the placement or if I just cannot do that treatment. Was your headache a direct result of where the botox was injected?

  • Chapreca
    5 years ago

    I’ve been doing Botox for a year and a half now & I guess I should consider myself one of the lucky ones…I went from having migraines 3-4 times/week to maybe 1every other month! Also, my insurance covers it w/no copay for me!! 35 years of suffering have come to an end…I can have my life back!

  • technopeasant
    5 years ago

    That’s wonderful. My insurance requires a $300 co-pay. I can’t afford that so it remains untried.

  • Sarah Hackley author
    5 years ago

    That’s fantastic! I’m so glad you’re having such great results from it, and that your insurance covers it 100%. What wonderful news! Thank you for sharing your story with us.

  • ClarissaS
    5 years ago

    Botox has been kind of the last resort in my treatment plan with my Headache Specialist. We have now gotten to the point where all of the other treatments have failed, so we began the paperwork for insurance approval. I have my first injections tomorrow, and am nervous and excited at the same time. I have tried my best to prepare for the possibility of this not working, and I know that it could take 2-3 sessions before it could work. Right now I’m averaging 6 days with Migraine or a higher level headache, most of the time it’s every day of the week. So any type of decrease in headache and migraine days I will take.

  • Sarah Hackley author
    5 years ago

    Good luck! I hope it works for you. Like Katie said, you sound well informed. That’s always a plus. 🙂 Let us know how it goes. Warm regards, Sarah

  • Katie M. Golden moderator
    5 years ago

    Good luck tomorrow!! You seem pretty well-informed about the procedure and have realistic expectations. Yes, it can take 2 or 3 sessions before getting the full effects. And right after the injections, you may have intense headaches or flu-like symptoms. This happens often after your first treatment as your body is getting used to the medicine. It doesn’t sound fun, but I promise it will subside and you should notice a decrease in intensity soon.

    Good luck and let us know how it goes!

  • Lifetime_Migraine_Sufferer
    5 years ago

    I too have had two rounds of Botox injections; one was the traditional migraine protocol and the other was a mixture of the migraine protocol and several other inflamed (painfully knotted) trigger points. I wasn’t lucky enough to have insurance pay for both treatments. One cost me $500 OOP and the other $3,000 OOP!! I can say with absolute confidence (and much disappointment) that neither protocol worked for me and in fact made my pain much more severe for several months. I can’t wait until medicine in the US advances to the point where they can 1) identify potential migraine responders to differing treatments, and 2) find a cure for those of us that suffer quietly everyday. Thank you for the enlightening article.

  • Sarah Hackley author
    5 years ago

    I’m so sorry that you have had such disappointing results, and that you had to pay so much out of pocket. I think we’re all hoping for new and improved medicines and treatment options soon. (And a cure!) Here’s hoping you find something that works for you soon. Warm regards, Sarah

  • ocprgmr
    5 years ago

    You might be able to get help with your copayment from Allergan. I did. Go to and find the option for savings or help with treatment cost. There is a form you fill out and a welcome package is sent to you. You may need to be proactive in making sure you receive your package.

    It took a couple of tries for me to get mine, but after submitting the EOB for my first treatment, I received a prepaid card with a balance matching my copayment — there’s a limit of $250 for first treatment and $100 for subsequent treatments. The card can only be used for medical/prescription purposes, I believe.

    I also believe there is an additional program for insurance that doesn’t cover BOTOX or for those who don’t have insurance, but don’t rely on that. Call them. They have been very helpful to me.

    BTW, my first treatment I could see an improvement. It didn’t last that long. The second treatment was delayed (insurance), and it didn’t help much at all. The most recent, 3rd, treatment helped faster and longer. I still have issues most every day; however, I’m able to DO something more often. Before the treatments I I was hardly able to do anything especially anything of a physical nature.

    I’m scheduled for my 4th treatment in a couple of weeks. I pray that it continues to help me.

  • Sara
    5 years ago

    From what I’ve read, The 3rd treatment is when you start seeing the full benefits. I have not tried it yet either. My neuro wants me to but I’ve been hesitant. It’s my next option if I do not improve on current treatment methods.

  • Krystolla
    5 years ago

    I tried botox but it didn’t work for me — my neurologist is pushing for me to try it again at a higher dose. If responsiveness to the treatment depends on peptides in the blood it doesn’t seem like changing the dose would make a difference.

  • chebbot
    5 years ago

    If you don’t have to pay a lot out of pocket, I recommend trying it again. It has a cumulative effect, and for me the first treatment helped, but the second helped more, then the third. I get them every 3 months and when I’m due I feel them coming back full force. So it’s worth a shot (harhar) if your insurance covers it.

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