Timolol Eye Drops for Acute Therapy of Migraine

            Acute migraine sufferers may find relief with beta-blocker eye drops     

This is a report on an eyedrop indicated by the FDA to treat glaucoma—Timoptic (Timolol).  It can also be used as an acute therapy drug for migraine that is safe with patients with medication overuse headache.  The dose is Timolol .05% solution as 1-2 drops in both eyes at onset, which may be repeated every 1-2 hours.

 Case building for this promising, yet unexplored therapy with push for clinical trial

October 15, 2015

Lynda Charters

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.

Reviewed by Carl Migliazzo, MD, and Robert Hagen III, MD

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.

Its 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.

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.

Dr. Migliazzo and Hagan are currently working with a private headache center to obtain grant money in order to carry out a prospective trial of the beta blockers in patients with acute migraine.

Carl Migliazzo, MD

E: Carl@Migliazzo.com

John C. Hagan III, MD

E: jhagan@bizkc.rr.com

Possible Side effects:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.  Contraindicated with asthma.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Change in eyesight, eye pain, or very bad eye irritation.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Very bad dizziness or passing out.
  • Very bad headache.
  • Slow heartbeat.
  • A heartbeat that does not feel normal.
  • Chest pain.
  • Trouble breathing.
  • Muscle weakness.