Timolol For Migraine 2024
All persons with migraine need to adjust their lives to live with such a chronic disease. It is not their fault that they have it. Migraine is genetic and clusters in families. Twenty percent of persons with chronic migraine are disabled. Migraine is a frequent reason for missing school or work. It is a common reason to go to the emergency room.
Many of the acute therapy drugs for treating Migraine have limits as to how often then may be taken without causing an overtreating problem—medication overuse syndrome. NSAIDS, triptans, ditans like Reyvow, and new CGRP altering drugs like Nurtec have limits as to how much may be taken.
Dihydroergotamine (DHE) can be used often but it comes as an outpatient injection intramuscularly or as Migranal nasal spray. There is a need for a quick, easy, outpatient treatment of Migraine patients with episodic or chronic Migraine which may come with medication overuse headache.
Therefore, with all these problems many migraineurs are left with their chronic headaches and limited therapeutic choices.
This is an article by Britt Talley Daniel MD, member of the American Academy of Neurology, the American Headache Society, migraine textbook author, podcaster, YouTube video producer, and blogger.
Timolol Eye Drops For Migraine . Timolol works successfully and quickly for preventive and acute Migraine treatment. It is a betablocker eye drop which works quickly, is easy to take, and is not a pill or a shot. It can be used for acute or preventive migraine therapy and doesn’t cause or aggravate Medication Overuse Headache. It is well accepted and has a low side effect profile.
Timoptic (Timolol) eye drops
What is the dose of Timoptic (Timolol)?
The dose for acute treatment of Migraine headache is Timoptic (Timolol) 0.25 or 0.5% solution as 1-2 drops in both eyes at onset, which may be repeated every 1-2 hours. There is no adjusting for renal impairment.
For prevention the usual starting dose is 10 mg twice a day. The usual maintenance dose is 20-40 mg per day.
Read my Mini Book on Migraine Here.
Aren’t betablockers like propranolol or aetenolol used for Migraine prevention?
Propranolol and aetenolol are oral pill medications that have a long history of use for Migraine prevention. These drugs must be taken daily and don’t work for acute MIgraine therapy..
What are possible side effects of using Timolol (Timoptic)?
hypersensitive to drug/class
asthma, bronchial
COPD, severe
heart failure, uncompensated
2nd or 3rd degree AV block
sinus bradycardia
cardiogenic shock
caution if bronchospastic disease, major surgery, diabetes mellitus, hyperthyroidism, myasthenia gravis, glaucoma, angle-closure, anaphylactic reaction history
Drug interactions of Timolol
CYP2D6 substrate, bradycardia, hypotensive effects
Safety/Monitoring of Timolol
No routine tests are recommended.
Pregnancy and Timolol
May use during pregnancy
Lactation and Timolol
May use while breastfeeding
Pharmacology of Timolol
Timoptic (timolol) non-selectively antagonizes beta- 1 and beta-2 adrenergic receptors.
Does Timolol have an FDA indication for acute treatment of Migraine?
Timolol has an FDA indication for prophylactic Migraine treatment. It can also be used for acute Migraine therapy. It has an FDA indication for treatment of Glaucoma which a problem of increased pressure in the eyeball.
Pertinent Literature articles
Migliazzo CV, Hagan JC III. Beta blocker eye drops for treatment of acute migraine. Missouri Med 2014; 111:284-289.
“Take home message—a small case series of patients has shown that use of beta-blocker drops may be a simple and inexpensive way to eliminate pain in patients with acute migraine.
Kansas City, MO : Millions of patients suffer from migraines and their physicians historically have gone through herculean efforts to find pain relief, but interestingly an inexpensive and effective drug may literally be sitting on the shelf and waiting to be tested in clinical trials.
Beta-blocker eye drops, used to treat glaucoma, have been shown in a series of patients to provide almost complete pain relief from acute migraine over years of use at very low cost to the patients.
Carl Migliazzo, MD, an ophthalmologist in private practice in Kansas City, MO, has been focused on investigations into the usefulness of this therapy for acute migraines for decades. John C. Hagan III, MD, who is also in private practice in Kansas City, recently joined Dr. Migliazzo in this effort.
Both investigators noted that while daily oral beta-blockers, such as timolol, betaxolol, levobunolol, metipranolol, and carteolol, have been used routinely to prevent chronic migraines, the drugs do not stop acute onset migraines after the onset of symptoms.
Timolol mechanism
The mechanism of action of the drops, the authors believe, is the passage of the beta-blockers into the nasal cavity and their rapid absorption into the blood vessels.
“Within a few minutes, the blood level of the beta-blocker is increased sufficiently to stop the escalating migraine headache," Dr. Hagan said. "This action would explain the success of the beta-blocking eye drops and the failure of the oral medications, as delivery through the eyes is much quicker than through the gastrointestinal system.”
In some of their most recent work published in the July/August 2014 issue of Missouri Medicine, the investigators evaluated the effects of timolol 0.25% and 0.5% and levobunolol 0.5% in seven women who used the eye drops when they first experienced migraine symptoms. According to Dr. Hagan, the women used these treatments over years, and the patients reported nearly complete pain relief and few adverse effects.
Comment by the author. “The Migraine process causes cerebral vasoconstriction which means tightening or narrowing of blood vessel diameter in the brain. Timolol, like all beta blockers, is a “vasonormalizer.” This means it prevents cerebral arterial constriction. Inderal (propranolol) was released to the American public in 1974 and is the first drug to have an indication from the FDA for prevention of Migraine.”
Case reports
Two representative cases showed the effectiveness of the beta-blocker therapy for acute migraines.
A 38-year-old woman had had migraines for 25 years. Her acute episodes were characterized by right-sided headache, nausea, vomiting, light and sound sensitivity, and confusion. Untreated migrainous episodes lasted 24 hours or longer. Relief sought with several oral treatments brought symptom relief after several hours.
She began instilling one drop of topical timolol 0.25% ophthalmic solution bilaterally with the first migraine symptoms with symptom relief after 10 to 20 minutes. On a scale of 1 to 10, the patient rated her relief as 8. She reported slight shortness of breath with bilateral instillation and now uses one drop in one eye with no adverse effects.
A 57-year-old woman, who began having migraines at age 5, complained of visual aura, unilateral headache, nausea, vomiting, photophobia, and confusion as her typical symptoms. Her migrainous episodes began with visual aura lasting 10 to 20 minutes following by severe pain above the right eye. The migraines usually lasted 4 to 6 hours following by a feeling of a hangover for one to two days.
About 27 years ago, she started using timolol 0.5% ophthalmic solution sublingually when the aura began. Improvement began in about 10 minutes and in 30 to 45 minutes the symptoms were completely relieved.
She also had asthma, but use of timolol did not cause breathing problems. In her mid to late 40s, she was able to discontinue use of timolol when the migraines stopped.
The investigator noted that not all patients with migraines are candidates for this treatment if they have asthma, other breathing problems, and some eye problems. The authors also stressed that these patients taking beta-blocker eye drops for acute migraine attacks be monitored closely.
Dr. Hagan noted that while this study had only seven patients, if the results could be replicated in larger placebo-controlled studies, this treatment approach could be beneficial worldwide.
Roadblocks
Dr. Hagan emphasized that beta-blockers have been reported to successfully eliminate the pain of migraine over the last 35 years. The first reports appeared in 1980 and were followed by others, but to date, no large clinical trials have been conducted. Dr. Hagan blames this on the fact that the drugs are available generically, which will provide little profit for the pharmaceutical industry to explore this treatment.
He emphasized that prospective, masked, controlled, randomized, clinical trials are long overdue and they could prove or disprove whether beta-blocker drops are useful for treating acute, even chronic migraines.
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By Ryan J. Cady, CEO Clivest Research; J. Kent Dexter, MD; Roger K. Cady, MD of The Headache Care Center in Springfield, Missouri.
USE OF BETA-BLOCKER OPHTHALMIC SOLUTION FOR THE TREATMENT OF MIGRAINE
Article Originally published by National Headache Foundation – http://www.headaches.org/2016/07/01/use-beta-blocker-ophthalmic-solution-treatment-migraine
In the annals of migraine, one of the most fascinating stories is how, in 1966, a physician named Robert Rabkin observed that the drug propranolol could prevent migraine. Dr. Rabkin was actually conducting a study using a beta-blocker (propranolol) to treat heart pain (angina) and fortuitously observed that one of his research subjects had a remarkable reduction in the frequency of his migraine attacks.
A decade later, Drs. Seymour Diamond and John Graham presented their experience treating 86 migraine patients with daily propranolol to the Food and Drug Administration (FDA), and demonstrated that propranolol was indeed efficacious and safe for migraine prophylactic therapy. Subsequently, propranolol became the first FDA-approved medication for the prevention of migraine.
As one of many beta blockers used commonly to prevent migraine, propranolol currently, is probably the most widely prescribed medication in the world for prevention of migraine. Beta blockers are used to treat multiple diseases including high blood pressure, heart pain, and irregularities of the heart as well as conditions such as anxiety and certain types of tremors. Beta blockers have been so successful that they are considered one of the most important medical discoveries of the 20th century.
In 1978, a second beta blocker, timolol, also received FDA approval as the first topical beta blocker for the treatment of glaucoma. Although clinical trials demonstrated a very strong benefit from using timolol as a migraine preventive, neither it nor propranolol have demonstrated efficacy as an acute treatment for migraine.
However, these previous studies have focused on oral preparations of these drugs and the drug was not absorbed quickly enough to be effective as an acute treatment. Interestingly, since the 1980s, there have been rare case reports of patients with glaucoma being treated with timolol eye drops who experienced migraine relief.
Considering the history of these beta blockers, two ophthalmologists—John Hagen and Carl Migliazzo—recently made a startling observation. During a game of golf, these ophthalmologists had an “eureka” moment while discussing possible treatment options for Dr. Hagen’s daughters who experience migraine.
They observed that some of their patients treated for glaucoma with timolol eye drops reported that if the timolol eye drops were instilled during a migraine, the headache would be rapidly terminated.
Following their discussion on the use of beta blocker eye drops for the treatment of acute migraine, Drs. Hagen and Migliazzo reported on a series of seven patients who had successfully treated acute attacks of migraine with timolol eye drops, which was published in The Journal of the Missouri State Medical Association in 2014.
The seven patients in these case reports were all female, ages 38 to 76, who presented with migraine syndromes, with and without aura. Five of the seven patients reported complete pain relief, with one patient reporting complete pain relief within 10 minutes of treatment. The two remaining patients reported pain relief of 8 and 9.5 on a 1 to 10 scale, with 10 representing complete relief.
These patients were all instructed to use 1 or 2 drops of their beta blocker eye drops as early as possible during their acute migraine attacks. Patients were advised to blink several times to encourage the eye drop to pass into the lacrimal drainage duct. Interestingly, one patient used timolol drops sublingually and reported receiving pain relief. The dye drops were generally well-tolerated with only one reported side effect of shortness of breath which only occurred if eye drops were used in both eyes.
Drs. Hagen and Migliazzo stress all patients underwent a complete medical history and ophthalmic examination prior to the initiation of topical beta blockers. Patients were advised to read the package insert and inform their primary care physicians of their acute use of beta blocker eye drops.
Since the publication of these reports, Drs. Hagen and Migliazzo have received multiple messages and phone calls from fellow physicians who have reported success with patients using beta blocker eye drops for migraine relief.
Although these represent only a few case reports, they provide additional evidence of the use of topical beta blockers in acute migraine, and the treatment appears to be well-tolerated. The physicians are hopeful to see the development of well-controlled studies to validate the efficacy of beta blocker eye drops for acute migraine relief.
HOW WOULD BETA BLOCKERS WORK IN ACUTE TREATMENT OF MIGRAINE?
The exact mechanism of beta blockers in the treatment or prevention of migraine is unknown. Beta blockers work primarily by blocking the stimulating or activating effects of adrenalin. Considering that individuals with migraine have inherited a nervous system that is more excitable than those without migraine, it is easy to assume that beta blockers may in some way reduce this inherent excitability.
In other words, the beta blockers may make the nervous system less vulnerable to migraine. While this likely explains the migraine prevention benefits, it also may provide a rationale for their use in the acute treatment of migraine headaches.
One can imagine that during a migraine, the threshold for nervous system activation has already been surpassed and hence the process of migraine occurs. Beta blocker eye drops enter the nasal cavity through the lacrimal duct (a small passageway from the eye to the nose that drains tears from the eye) very quickly.
Once in the nose, the eye drops are rapidly absorbed into the blood. Conceivably, they could block the activating effects of adrenaline and allow the nervous system to reverse migraine. Beyond the speed of entry into the blood, another major advantage of nasal absorption is that medications do not have to pass through the liver before entering the systemic circulation, thus avoiding their metabolism by the liver and allowing a much smaller dose of medication to be effective. Beta blockers have also been found to reduce the electrical excitability of nerve cells, and this too may be part of their potential mechanism.
When oral preparations of beta blockers are used to prevent migraine, levels build up slowly in the blood. This action works well for prevention but during migraine, these levels would increase too slowly to be effective. Using an eye drop with rapid absorption through the nose circumvents that problem.
Also, nerves in the nasal cavity may become activated and potentially, beta blockers could act directly on these nerves. Finally, it is possible that some of the beta blocker eye drop could be absorbed into the brain and exert their beneficial effect in that manner.
WOULD BETA BLOCKER EYE DROPS BE A BREAKTHROUGH FOR THE ACUTE TREATMENT OF MIGRAINE?
Currently, the medications used to treat acute migraine generally are either triptans or nonsteroidal anti-inflammatories (NSAIDs). Triptans act by constricting blood vessels and blocking the release of calcitonin gene-related peptide (CGRP) from the nerves activated during migraine. CGRP cause blood vessels to swell and initiates the cascade of inflammatory events leading to pain.
The NSAIDs are believed to work primarily by blocking the synthesis of another inflammatory pathway mediated by prostaglandins. If beta blockers are found to be an effective acute treatment for migraine, their efficacy would likely be due to a novel mechanism(s) and provide a third line of potential treatment success. This finding would undoubtedly represent a major medical advancement for the acute treatment of migraine.
Also, because beta blockers are already used on a daily basis to prevent migraine, it is likely that their frequent use to treat acute migraine would be associated with medication-overuse headache.
This finding would welcome news for those individuals with high treatment requirements. The beta blocker eye drops also would likely have a good tolerability profile as the dose of actual medication received would be quite low relative to oral beta blocker therapy. Clearly, the need to obtain good clinical trials is indicated before making claims for their use of safety.
WHAT ARE THE RISKS AND LIMITATIONS?
Oral beta blocker therapy is not tolerated by everyone. Beta blockers can lower blood pressure and slow the heart rate. These effects have been occasionally noted with beta blocker eye drops as well. Rarely, beta blockers can have an adverse effect on asthma. Finally, for those patients with diabetes who are prone to hypoglycemia (low blood sugar), beta blockers can mask some of the warning symptoms and would have to be used with caution. However, beta blockers, and in particular timolol, have been used for decades on a daily basis for treatment of glaucoma, and are generally well-tolerated even with daily use. It is assumed that as an acute treatment for migraine, the beta blocker eye drops would be used on an intermittent basis which should increase their tolerability. In the future, studies may be conducted on the administration of beta blockers as a nasal spray.”
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Britt Talley Daniel MD
