bottle of timolol maleate drops for migraine
Medication,  Migraine,  Research,  Science/Research,  Timolol

Timolol Eye Drops For Migraine: Is It The Right Abortive for you?

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John C. Hagan

Medically reviewed by John C. Hagan, III, MD, FACS, FAAO

Timolol eye drops for migraine is a big topic of conversation in our private Facebook group. Why would glaucoma eye drops be so interesting to people with migraine? A couple of small studies have shown Timolol maleate ophthalmic drops (0.5% solution) to be effective for treating acute migraine attacks. 

This article will explore how timolol for migraine and vestibular migraine can be an effective and less expensive option for treating attacks. The goal is to give you information to evaluate if Timolol maleate eye drops 0.5% ophthalmic solution is an appropriate treatment to discuss with your doctor. 

** This is written from the patient and patient-advocate perspective and is for the purpose of education and sharing of experiences. The topic concerns medications. Any changes in medications should be discussed with your doctor.  This is not medical advice. **

A special thanks to Dr. John C. Hagan for providing the links to studies and papers about Timolol eye drops for migraine as well as commentary for this article.

Glaucoma eye drops (for migraine too?)

Timolol eye drops have been used to treat glaucoma since 1978. Beta blockers for glaucoma are one of the most commonly used classes of medication. They work by reducing the amount of fluid produced in the eye thereby reducing pressure build up in the eye. (11) Timolol has a low side effect profile and is inexpensive. The length of time on the market has shown that the eyedrops are safe and well tolerated with proper patient selection and monitoring for side effects. (10)

Timolol is available as a generic and is also available in a preservative-free formulation. Beta blockers can lower blood pressure and is a concern for many with migraine. This drop in pressure was measured by a study and showed the the average drop in diastolic (3.8%) and systolic pressure (2.8%) was less than 4%. (1) This article is reviewing how these glaucoma drops might work for acute migraine attacks.

Beta blockers for migraine: How they work

Oral beta blockers (propanolol, metoprolol, timolol) are very effective in preventively treating migraine. Beta blockers seem to work by stabilizing blood vessels and limiting their ability to over dilate. They can also reduce the excitability of the nervous system, serotonin and anxiety. (2) Slow absorption into the blood stream makes the oral beta blockers ideal for the prevention of migraine attacks, but this same absorption rate makes them ineffective for treating acute attacks. Most migraine attacks are well under way within 30 minutes and then they become more difficult to effectively treat. This is why headache specialists encourage migraine patients to treat at the first sign of an attack.

How do Timolol eye drops work for migraine?

“Beta-blocker eyedrops absorbs quickly into the lacrimal duct or sublingually and gets an 80% or greater beta blockage within 15 minutes”. (3) Oral beta blockers take 1-2 hours to reach peak plasma limits which makes them a poor option for treating attacks acutely. While the studies conducted on timolol drops for migraine have been small, the results were a “reduction of pain score by 4 points, or to zero, 20 minutes after instillation of the eyedrop.” (4) Out of the 233 migraine attacks treated with timolol eye drops for migraine during this study, 82% met this reduction in pain. (4)

How to use Timolol drops for migraine

The instructions for use of timolol eye drops for migraine (0.5% ophthalmic solution) is one drop in each eye at onset of migraine symptoms (aura or attack). If the pain is not resolved in 10 minutes, a second drop in each eye can be added. (4) Because eye drops can be hard to instill, Timolol drops for migraine relief used sublingually (under the tongue) and as a compounded nasal spray (more on this below) are also effective for relief. These methods can achieve more reliable systemic absorption. (5)

As mentioned above, beta blockers can help to stabilize the dilation of blood vessels, reduce anxiety, serotonin and nervous system excitability. This makes it an ideal treatment for migraine. The benefit of Timolol eye drops for migraine attacks is the quick absorption rate which allows treatment to be effective in about 15-20 minutes. “Topical beta blocker eye drops provide significant blood levels sufficient to provide beta-blockade within minutes of administration; an ideal pharmacokinetic feature of an acute migraine medication.” (6)

Compounded timolol nasal spray – available by authorized prescribers.

In 2019, a compounded Timolol nasal spray was developed and is available to authorized prescribers (only O’Brien Pharmacy at this time). The patients who should avoid the Timolol nasal spray for migraine are similar to the ones that should avoid the Timolol eye drops. (7)

Avoid the compounded nasal spray if you have:

  • Reactive airway disease
  • Marked bradycardia (slower than normal heart rate (less than 60 beats per minute)
  • Hypotension (low blood pressure – 90/60mm Hg and below)
  • Previous history of problems with beta blockers 
  • Already on a beta blocker

This list is not inclusive and you should not start beta blockers without the approval of your physician.

How to use compounded Timolol nasal spray

Shake bottle and swiftly apply one spray per nostril. If no improvement in 10-15 minutes, it may be repeated a second time. 2 sprays in each nostril is the max allowed dosage in 24 hours. (7) Delivering rapid release beta blocker to the nasal mucosa is as effective as an intravenous delivery. (7)

Timolol as part of a migraine cocktail

Other medications can be taken at the same time as these glaucoma eye drops for migraine including NSAIDs, triptans or ergot alkaloids. (5) Some benefits of rapid onset beta blockers are reducing blood pressure, slowing the heart rate and reducing the effects of anxiety. This makes timolol nasal spray or eye drops a unique medication to add to a migraine cocktail.

Recommendations of headache specialists 

Headache specialists who have reviewed the studies agree that using rapid onset beta blocker drops make sense for acute migraine treatment. They also agree that large scale randomized placebo controlled studies are warranted. (8, 9, 6)

Cost benefit, long term safety and low side effect profile

The new migraine specific CGRP medications are exciting to both the market and patients. However, they are not without side effects or even lack of effectiveness in many patients. Side effects are one of the most talked about topics in our private Facebook group. Many are burned out by the number of medications they have tried. As well as the copious side effects and those which have failed to provide relief. 

Timolol has shown to have very few side effects and is well tolerated by patients. (9) It doesn’t have the added worry of rebound that other migraine abortive medications do, like NSAIDs and triptans. It is also inexpensive and widely available. This benefit can’t be emphasized enough. The average cost of a bottle of Timolol maleate 0.5% ophthalmic solution is a fraction of the cost of the new CGRP medications. It would be a huge benefit for people who are trying to figure out how to afford effective medications to have the option of trying Timolol for migraine. Especially because the manufacturer’s patient assistant programs for the new CGRP meds are unavailable for those without commercial insurance. 

While the study sizes are small, Timolol, glaucoma eye drops for migraine, showed significant promise for acute migraine attack relief. The next step is to invest in larger studies to verify what has already been observed. “The encouraging positive response of the acute migraine in these patients supports the need for a prospective, randomized and masked study of a topical beta-blocker.” (9)

Personal Experience – Timolol eye drops for migraine review

My personal experience with Timolol for migraine is very favorable. I started taking the drops a couple of years ago at the first sign of an attack. Typically, the Timolol drops work well to abort my migraine attack. If I catch it early, it will take care of the attack by itself about 80% of the time. The other 20% requires other acute medication or ginger to be completely effective. Overall, I feel the Timolol eye drops for migraine attacks are effective for me. I am grateful for the opportunity to use them at the first sign of migraine attacks. This limits reaching for more expensive medications with more side effects. 

Timolol eye drops for vestibular migraine

One of the other Migraine Strong writers also uses Timolol eye drops for her vestibular migraine. Jennifer Bragdon has found the eye drops to be effective as well. Especially for head pressure associated with her vestibular migraine attacks.  She reaches for the eye drops for either a painful attack or a vertigo attack. Jenn’s use of these glaucoma eye drops for migraine is a key part of her prescribed treatment and is listed in the review of her vestibular migraine recovery plan.

Difficulty in obtaining a prescription

Along with those that have found Timolol eye drops to be effective for migraine prevention and acute treatment, there are an equal number who can’t get a prescription to try them. Many doctors are uncomfortable prescribing a medication that is so far out of their lane. Especially when there is no formal guideline for how to prescribe for migraine. Many neurologists who agree to a trial prescription require patients to first see an ophthalmologist. Dr. John C. Hagan III, ophthalmologist and author of studies and articles on Timolol maleate eye drops for migraine as well as Editor of Missouri Medicine: The Journal of the Missouri State Medical Association, agrees that this is a good idea.

Dr. Hagan’s input

Dr. Hagan was kind enough to provide his thoughts on Timolol through a Migraine Strong email interview. “Timolol is a beta blocker and all physicians should be aware of who should not be prescribed these medications and side effects to watch for if used. This is not an inclusive list but very slow pulse, very low blood pressure, asthma or wheezing history (as well as those who’ve had) previous problems with beta blockers.  Timolol eye drops will also not work on anyone already on a beta blocker, or who has tried unsuccessfully in the past with daily beta blocker pills for chronic migraine prevention. 

Beta blockers slow the pulse, lower blood pressure and provide some anti-anxiety relief. This is helpful for most migraine patients. For people using the timolol eye drops with the approval of their physician and that are using other oral acute migraine medications and trying timolol drops under the tongue: at first sign of acute migraine take your other migraine pills first and then quickly put the timolol drops under the tongue and try not to swallow for several minutes or drink for 10 minutes or more.

There are also some patients with eye problems that should not take timolol eye drops; the safest thing would be to ask the patient’s ophthalmologist or optometrist for an okay or if they have not had a recent eye exam or don’t have an eye doctor to have an exam to get clearance.  The Missouri Medicine articles we wrote noted that some patients prefer to take their medication under the tongue (sublingual); all recommendations however would need to come from the treating physician. As this is an off label use, only the treating physician can tell patients if they should try the beta blocker drops. This is not an endorsement of off label use of timolol eye drops by me.”

Timolol migraine reviews

When we reached out to our private Facebook group (over 16,000 members) most said they had never heard of it or reported frustration with doctors reluctant to prescribe it. Our role as migraine educators is to spread the word about new treatment options. Those in the group that had tried the glaucoma eye drops for migraine found them to be effective in treating their migraine attacks.

Hopes for Timolol

Around 60% of people with migraine express dissatisfaction with their acute medication. (3) This includes the new CGRP medications and well established triptan and ergot alkaloid formulations. Having another inexpensive medication to trial, with a long history of use and low side effect profile, would offer hope to many. 

When asked what his hopes for Timolol eye drops for migraine were, Dr. Hagan said “Hopefully it will be studied with larger groups of patients in FDA studies financed by grants or a pharmaceutical company.  Over time timolol in solution form (not pills), the hope would be that large scale, placebo-controlled studies would lead to approval for acute migraine like beta blocker pills are for chronic migraine prevention.”

Migraine Strong’s hope is to see a larger scale study and prescribing guidelines to make Timolol eye drops easier for patients to try and doctors to prescribe.

References:

  1. https://pubmed.ncbi.nlm.nih.gov/7019560/
  2. https://headaches.org/2007/10/25/beta-blockers/
  3. https://pubmed.ncbi.nlm.nih.gov/32401737/
  4. https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2771168
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312162/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179475/)
  7. https://pubmed.ncbi.nlm.nih.gov/32401737/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179459/
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179464/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270356/
  11. https://patient.info/medicine/timolol-eye-drops-for-glaucoma-timoptol-tiopex

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Timolol Eye Drops For Migraine: Is It The Right Abortive for you?

I began having migraine attacks when I was a teenager, but was never properly diagnosed until I was an adult. This began 18 years where I was chronic and mostly intractable, resulting in a migrainous stroke in the summer of 2014. By implementing the protocols from the Heal Your Headache book by Dr. David Buchholz and the Migraine Strong Treatment Pie, I have been able to reduce my migraine frequency to episodic and maintain that since 2015. The end result of continuing to practice these tools is being able to actively participate in my life as a wife, mother, family member and friend. My goal as a migraine advocate, educator, and wellness coach is to help others gain more control over migraine. Let us know how we can help.

9 Comments

  • Judy

    I think this would work for me but I am already on a Beta blocker (very high dose) for high BP. If it is just a little dose in the eye, would it really be a problem? My eyes water so much especially before and duing a migraine.

    • Migraine Strong

      From my understanding of the research, taking an oral beta blocker means that you already have a near 100% beta blockade going on. So adding another to what you are already taking may not be effective. I think it is something to discuss with your doctor for sure. Good luck!! -eileen

  • Charles Lederer

    Congratulations to Eileen for her article on using timolol as a method of prevention of migraine, administered at the first symptoms of an attack. To introduce myself, I am an M.D., an ophthalmologist.
    Perhaps I can fill out a little more on this topic. Eileen interviewed Dr. Hagan for her timolol article. He has played an important role in disseminating and explaining this concept. Dr. Hagan happens to be my good friend.

    There is a pretty good story behind the story concerning this topic. A few years ago Dr. Hagan, Dr. Carl Migiazzo, and I, all three of us Kansas City ophthalmologists, were playing a round of golf. Dr. Migliazzo actually was the inspiration for this technique of treatment of acute migraine. His wife is a migraine sufferer. Experiencing her migrainous misery with her, at one point he wondered if administering a drop of timolol in each eye at the very start of a migraine could abort an attack She tried it, and obtained very significant relief with this approach. He then suggested his migraine-affected office staff try it, and enough of them responded that he felt fairly convinced that he had discovered something that was potentially very important.

    In between us grumbling about our less than skillful golf shots, Dr. Migliazzo discussed his observations with Dr. Hagan and me. We were fascinated about the potential for this common, inexpensive, relatively safe and well-tolerated medication helping those who suffer with migraine. We started telling migrainers we knew, our patients and others, to try this approach, and both of us were quite impressed by how many migrainers responded to this approach. Some migraine patients were incredibly grateful, and overwhelmed by how it had changed their lives for the better.

    There is a very critical concept that must be understood to explain how this approach to migraine actually works when timolol (developed for treatment of glaucoma), is administered as an eye drop. When people use eye drops to treat eye diseases, the intent is to have the drop absorb into the eye to achieve the intended purpose. However, inevitably some of the drop escapes from the surface of the eye through a passageway, the lacrimal canal. The lacrimal canal is the “drain” of the eye. https://www.medfriendly.com/lacrimal-canals.html This canal drains tears (and eye drops) into the back of the nose. This canal explains why when people cry they need to blow their nose–the tears flow down through the canal to the back of the nose.

    The tissue around the eye, and the lacrimal canal, and the inside of the nose (and mouth) is lined by mucous membrane. The mucous membrane (slick, smooth tissue) is porous to medication and allows drugs (like timolol drops) to enter the bloodstream virtually immediately. This is much different than when timolol in pill form is administered orally. A pill needs to first dissolve in the stomach and small intestines. The medication in the pill, by this time dissolved in the blood, has to pass through the liver to be dispersed to the rest of the body. As the medication passes through the liver it is metabolized, which inactivates a variable percentage of the medication. After those steps the active drug finally enters the bloodstream.

    An eye drop, since it is absorbed by mucous membrane, is not metabolized by the liver but instead is absorbed into the bloodstream so quickly and efficiently that, in effect, it is more like an IV injection of the eye drop medication. This is the unique and special concept that explains why an eye drop, like timolol, can be effective in treating migraine at the very start of an attack–it gets into the system very quickly, without being processed by the liver.

    As mentioned above, mucous membrane lines the inside of the mouth. The sublingual area (the area under the tongue) has a high concentration of blood vessels. Sublingual administration of timolol is considered a more efficient way to administer the medication for our purpose, since it is sometimes hard to hit the eye with an eye drop and some of the drop always spills out over the eyelids and gets wiped away.

    To administer it sublingually, do this: Tilt your head back, or, even better, lie down on your back. Open your mouth widely. Place your tongue up on the roof of your mouth. Drop two drops of timolol into that space between your lower teeth and the under surface of your tongue. Ideally, someone else could more easily hit that target for you. After that, close your mouth and try to keep the drop, as much as possible, under the tongue, so a high concentration of the timolol drop is in contact with the sublingual blood vessels, allowing better absorption into the body. Don’t drink anything, and try not to swallow, for 10 minutes or so.

    Keep in mind that timolol can have systemic side effects and should not be overused. If a total of two drops are administered sublingually, with confidence that they were placed effectively, I would be reluctant to recommend repeating another dose of the drops.

    In terms of obtaining a prescription for timolol drops to use in this way, realize that doctors may not be aware of this way of treating migraine, and, admittedly, on the surface it is kind of an unusual treatment. Naturally enough, this would cause them to be very reluctant to become involved with this unique and off-label approach. Something that might be beneficial would be to copy a couple of scientific studies that describe the technique and hand them to the doctor for their analysis.

    Charles Lederer, M.D.

    • Migraine Strong

      Thank you for this comment Dr. Lederer! We so appreciate the work all of you are doing on behalf of all patients with migraine! As an aside, some of my best thinking is accomplished on the golf course!!

  • Charles Lederer

    Please check out my comment below. The very special feature of the timolol drops is how quickly it gets into the bloodstream, which seems to be the secret to its success when used at the first sign of an incipient migraine.

    If may not work as well, or at all, if a person is taking an oral beta blocker on a regular basis, but if I were you I would consider giving it a try since it is so (relatively) inexpensive and because you have proven that you tolerate beta blockers.

    C. Lederer, M.D.

  • Brittani

    I am extremely interested in trying this medication. I am going to ask my neurologist about it. He is always trying to suggest a medicine that is used for mental illnesses (which most migraine preventatives are) and I have had a bad experience with one. So, I don’t want to take one anymore. I do not like taking medications at all and have tried all natural things instead; not really working. Maybe I didn’t try them long enough. I get vestibular migraines. Which is almost NEVER accompanied with a head pain. Maybe when there is head pain is when I am having an attack? It’s hard for me to distinguish because I am dizzy and off balance about 24/7. Everything I do affects this. In turn, when I am having these symptoms I am confused as to whether I am actually having an attack or if I’m just presenting these dizzy vertigo symptoms (because they can be there even when you’re not suffering an attack.) my symptoms started suddenly about a year after I had my daughter (9years ago) and have been prevalent since. I am needing something to help me with this. The most frustrating part that I cannot deal with is the constant dizziness. It keeps me from performing functions. It prohibits me from enjoying life. It is miserable.

    • Migraine Strong

      I hope you get a chance to try them if they are appropriate for you with your medical history. Dr. Hagan who was interviewed for this article thinks seeing an ophthalmologist prior to starting is a good idea. It would likely also help your neurologist feel more comfortable with dispensing them. Dr. Shin Beh is a well known ‘dizzy doc’ and he prescribes them for vestibular migraine. We highly recommend his book which is listed in our Favorites section on the website. Vestibular migraine attacks don’t always have head pain. Sometimes it is primarily dizziness, vertigo, pressure in the head and ears and feeling off balance. I hope you get to try the Timolol eye drops and that it works for you!! -eileen

  • cheril

    I also get vestibular migraines. I never get pain in my head. Ive been saying for years an eyedrop would help and I thought a steroid eyedrop would work. I have to take a Medrol dose pack to rid of the migraine. I also get hemi plegic migraines so I cant take the new anti CGRP meds. tried everything else, nothing works but prendisone. I have mixed connective tissue disease so I thought the eyedrops with steroids would work. But Im going to ask my dr. about the eyedrops in this article.

    • Migraine Strong

      I hope they work well for you! Why can’t you use the new CGRP meds with hemiplegic migraine? I know many people who are on them with that type of migraine. Just curious. -eileen

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