Predicting response to Botox injections

A good predictor of response to Botox injections in chronic migraine patients has been found by Spanish researchers.

While Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain, it does not help everyone. Approximately 30% of patients with chronic migraine headaches do not respond to Botox. We usually try at least two sets of injections three months apart before considering the patient to be a non-responder. Considering that Botox is an expensive treatment, it would be very useful to know beforehand which patients will respond and which will not. Besides the cost, it would also save patients time, during which they could be trying other treatments.

Some studies show that having a constricting headache or pain in the eye is usually a positive predictor of response to Botox. On the other hand, exploding headache (that is when the pain is felt pushing from the inside out), is less likely to respond to Botox injections. However, these are very subjective descriptions and predictions based on them are not that reliable.

A new study by Spanish researchers just published in the journal Headache reported that the levels of CGRP (calcitonin gene-related peptide) and VIP (vasoactive intestinal peptide) in patients’ blood are good predictors of response to Botox in chronic migraine sufferers. These two chemicals, which circulate in the blood and perform various important functions in the brain have long been the subject of scientific research. Actually, we think that Botox works by blocking the release of CGRP from the peripheral nerve endings. Dr. Julio Pascual and his colleagues measured the levels of these two chemicals in chronic migraine patients before they were treated with Botox. Botox was administered according to the standard protocol every 12 weeks for at least two treatment cycles. A patient was considered a moderate responder when both: 1) moderate-severe headache episodes were reduced by between 33 and 66%; and 2) subjective benefit on a visual scale from 0 to 100 was recorded by the patient of between 33-66%. Patients were considered to be excellent responders when both items improved by more than 66%. Those without improvement of at least one-third in the two items were considered as nonresponders.

The study involved 81 patients with chronic migraine and 33 healthy controls. CGRP and VIP levels were significantly increased in the chronic migraine population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. The probability of being a responder to Botox was 28 times higher in patients with a CGRP level above the threshold.

The measurement of CGRP and VIP is done only by research institutions and is not yet offered by commercial laboratories. However, considering how much money can be saved by not giving Botox to those who are unlikely to respond, these tests should become widely available once these findings are confirmed by other researchers.

  1. Dr. Mauskop says: 11/05/201510:44 am

    Yes, some people need to get Botox more often than at the standard 12 week intervals. I have many patients who get Botox every 10 weeks and a few who need it even every 8 weeks. The main problem we encounter is convincing insurance companies to pay for more frequent Botox injections. Some allow it, but many will not agree to pay for a treatment even a day sooner than 12 weeks.

  2. Adam R. says: 11/04/20153:08 pm

    I had two rounds of Botox for chronic migraine. The first round took 3 weeks to work but I was migraine free for 5 weeks! Then the headaches returned, I am assuming because the Botox wore off. My second round was not as dramatic for I am having more migraine days then before (but also having sleep difficulties which is a big trigger for me.) I am hoping that it doesn’t mean Botox isn’t working, especially since I had 5 weeks relief the first round. I am back in a migraine cycle and want to move my third round of Botox up a week (10 weeks instead of 11). Just wondering if others can receive Botox at 10 weeks since for me it seems to wear off at 8 weeks. Thank you

  3. Dr. Mauskop says: 11/03/20154:50 pm

    The development of antibodies to Botox is very rare, but certainly can happen. The question usually is whether Botox stopped helping or the patient developed antibodies. In case of antibodies, you would not have lost your wrinkles and the ability to move your eyebrows up and down. To confirm the presence of antibodies we give a test dose into the forehead muscles to see if they get paralyzed. A blood test for Botox antibodies is also available, but this clinical test is more reliable. If antibodies are indeed present, changing the protocol does not help, but switching to botulinum toxin type B (Myobloc or rimabotulinumtoxinB) can. The other two available botulinum toxin products on the US market (Dysport or abobotulinumtoxinA and Xeomin or incobotulinumtoxinA) are type A, so those will also be ineffective if antibodies to Botox are present.
    Typically Botox stops helping not because of antibodies, but due to an increase in headache triggers, such as stress, lack of sleep, alcohol., which seems to be the case with you.

  4. Jamie says: 11/02/20158:26 pm

    Dr. Mauskop, I’m wondering if you could provide more information on your experience with the development of antibodies to botox and loss of effectiveness of injections over time. I am a chronic migraine sufferer and also a physician. I started receiving botox injections about a year ago and they were very helpful for the first six months. However the last two injections have been minimally effective (though there were other factors at play as well that may have worsened headache frequency). Do you recommend ongoing injections? Other changes in protocol to improve effectiveness?

  5. Dr. Mauskop says: 04/12/201411:46 am

    Yes, neck and shoulder muscles are often injected with Botox. The effect lasts 10 to 12 weeks. Usually, each subsequent treatment is better than the one before. So, the first treatment may give 30% relief, the second, 60% and the third, 90%. Symptoms other than pain in the head, eyes and ears, such as light and noise sensitivity, brain fog, and other are also usually relieved. You can see how typical Botox injections are done on this youtube video I recorded –

  6. Holly says: 04/11/201410:50 pm

    Thanks! Do they inject it in the neck like they do cortisone shots (have not had those before)? I am in the military, so hopefully should have no problem with getting it. Moving this month, but the moment I settle I am going to pursue inquiring about Botox for SURE & will try to update you down the road as a guinea pig, ha. I saw it was given every 12 weeks for a couple/few treatments….do you have an idea how long it works on the patients once tried & if it has helped with some of the other symptoms caused by the headaches? My other weird things may not be caused by the headaches themselves, as they may be independent of what ever else may be going on, but I’m wondering if the Botox at least helps with the light/sound sensitivity, along with maybe the face burning/numbness & eye pain/blurriness & ear pain/burning. Based on suggestions, I started alternating the Magnesium Citrate & Magnesium Aspartate along with about 3000mg Vit D3. Like I said, I’m desperate, so I’m trying anything! Thanks again!

  7. Dr. Mauskop says: 04/11/20148:06 pm

    Yes, Botox can help regardless of the type of headache. Researchers are looking at various predictors of response, but at this point it is trial and error. But in case of Botox, unlike with medications, the error or rather side effects are minimal, so it is worth a try. COnsidering that you’ve tried so many prophylactic medications, most insurance plans will cover Botox.
    We think that the way Botox works is by stopping nerve endings in the scalp from responding to messages that come from the brain. Without this response from the periphery, the brain does not get wound up and the headache is prevented. Since you work as a nurse in an ED you may want to ask a doctor to give you IV magnesium, unless you have kidney problems or another contraindication. Oral magnesium often does not get absorbed well. Keep us posted.

  8. Holly says: 04/11/20144:53 pm

    Just ran across your blog today –ever searching for headache HELP, of course. I’m 37, work as an ED nurse, love my job & don’t have any unusual stress that I notice from normal & no Hx depression. Last year, I started developing strange, miserable headaches that got worse & worse & lasted longer & longer until I finally dragged myself to my Dr. Many other symptoms started after this whole mess, but my Docs cannot figure out what they are from yet (though we have tested several things & I have seen MANY specialists). One of my neurologists believe they are “secondary” headaches/migraines, but don’t know what “from”. They tell me that “we will have to just wait & see what else presents itself” (if anything, which I hope nothing else starts, because all of this has been ENOUGH!). Most medications have not helped besides steroids when this first started last year; & propranolol at least helps keep it from escalating to ‘really’ bad –because it keeps my heart from palpating with them, which in turn makes my head pressure/burning worsen into POUNDING with my pounding, fast heart.
    My question after all that rambling is, have you heard if it is only a particular headache/migraine that Botox helps? Past pain management Dr’s have spoken to me briefly about botox, but didn’t really explain how it worked. Neurologists are at a loss as to what meds to try (without using anything heavy, as I need to function in my serious job!). I initially tried my own methods of NSAIDS/Tylenol/Aspirin/hydration. In addition to the more helpful steroids/Propranolol, we’ve tried Imitrex, Zomig & Maxalt -takes ‘edge’ off at times, Nortiptyline -no help-, & Topamax -no help & made some other symptoms worse. Rarely Phenergan for nausea/dry heaving. I just read about Magnesium, so have started that on my own for the past couple weeks. I’m getting desperate & am thinking about asking about the Botox. Do you know how they inject it & does it have any side effects for this use? Thanks for any info if you are able 🙂

  9. Holly says: 04/11/20144:13 pm
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