Migraine Medications for Tinnitus

Overseen By Amanda Francis

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Irvine

Disqualifiers: Pregnancy, Adverse medication reaction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Tinnitus represents one of the most common and distressing otologic problems, and it causes various somatic and psychological disorders that interfere with the quality of life. Despite too many research projects on finding the mechanism of tinnitus, its pathophysiology remains poorly understood. It is well understood that many factors, such as poor education, lower income, or occupational, and recreational activity associated with high noise exposure, influence the prevalence and risk of tinnitus. Although the economic and emotional impact of tinnitus is large, there is currently no FDA-approved medication to treat this condition. However, there are pharmacological options to address the stress, anxiety, and depression that are caused by tinnitus. In this project, the investigators intend to use medications for patients with acute tinnitus to decrease the impact of tinnitus in their daily lives and activities. There are some studies on medications treating tinnitus; however, there are few randomized clinical trials to prove the efficacy of the treatment. The frequency and loudness of tinnitus will be measured before and after the course. Functional MRI of the brain will be obtained to view any changes that may occur before and after the treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is it safe to use migraine medications like Nortriptyline, Paroxetine, Topiramate, and Verapamil for tinnitus?

Topiramate and Verapamil, used for migraine prevention, have been studied for safety in humans, but they can have side effects that vary in severity. It's important to balance their potential benefits with the risk of side effects and discuss with a healthcare provider. ^{1 2 3 4 5}

How does the drug combination of Nortriptyline, Paroxetine, Topiramate, and Verapamil for tinnitus differ from other treatments?

This drug combination is unique because it uses medications typically used for migraines and depression, such as Nortriptyline (a tricyclic antidepressant) and Topiramate (an antiepileptic drug), to address tinnitus, a condition with no standard drug treatment. This approach leverages the drugs' effects on neurotransmitter systems and neuronal excitability, which are also involved in tinnitus. ^{1 2 3 4 6}

What evidence supports the effectiveness of the drugs Nortriptyline, Paroxetine, Topiramate, and Verapamil for treating tinnitus?

Topiramate, an antiepileptic drug, is being evaluated for migraine prevention and has shown some effectiveness in reducing migraine frequency, which may suggest potential benefits for related conditions like tinnitus. Additionally, tricyclic antidepressants like Nortriptyline have shown benefits in migraine prevention, which could imply some effectiveness for tinnitus, although direct evidence is lacking. ^{1 2 4 6 7}

Who Is on the Research Team?

Mehdi Abouzari, MD, PhD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for individuals experiencing acute tinnitus, which is a persistent ringing in the ears. Participants should not have any FDA-approved medication for their condition and are looking to reduce the impact of tinnitus on daily life. Details about specific inclusion or exclusion criteria were not provided.

Inclusion Criteria

I am between 25 and 85 years old.

Subjects must be compliant with the medication and attend study visits

Must be able to read and write in the English language to provide consent

Exclusion Criteria

Subjects with a history of an adverse reaction to medication being prescribed

Subjects suffering from a medical condition or have a history that may be concerning to the investigator's clinical opinion

I have no health conditions that prevent me from taking certain medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nortriptyline plus topiramate or verapamil plus paroxetine for 8 weeks, with weekly dosage adjustments based on symptoms

8 weeks

Weekly phone check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nortriptyline
• Paroxetine
• Topiramate
• Verapamil

Trial Overview The study tests if migraine medications (Verapamil, Nortriptyline, Paroxetine, Topiramate) can help manage acute tinnitus. It measures changes in the frequency and loudness of tinnitus before and after treatment using surveys and functional MRI scans.

How Is the Trial Designed?

Group I: Group V-P Active Control 2 Interventions

Verapamil (starting dose 30 mg) plus Paroxetine (starting dose 4 mg) with appropriate dosage increase as necessary. The reported symptoms will dictate dosage adjustments. If symptoms do not improve, patients will be advised to increase their dosage by adding one additional pill, which equals an increase of verapamil by 30 mg and paroxetine by 4 mg, for one week until the next phone check-in. This process will continue until the patient reaches a maximum of 240mg of verapamil plus 32mg of paroxetine for the duration of the 8 weeks (a total of 8 pills of each combination).

Group II: Group N-T Active Control 2 Interventions

Nortriptyline (starting dose 7.5 mg) plus Topiramate (starting dose 10 mg) with appropriate dosage increase as necessary. The reported symptoms will dictate dosage adjustments. If symptoms do not improve, patients will be advised to increase their dosage by adding one additional pill, which equals an increase of nortriptyline by 7.5 mg and topiramate by 10 mg for one week until the next phone check-in. This process will continue until the patient reaches a maximum of 60mg for nortriptyline plus 80mg for topiramate for the duration of the 8 weeks (a total of 8 pills of each combination).

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

Divalproex sodium, the only FDA-approved antiepileptic drug for migraine prevention, significantly reduced migraine frequency by 30% to 40% in patients over 12 weeks, with nearly half of the patients experiencing a 50% or more reduction in headache frequency.

Gabapentin also showed significant efficacy in reducing migraine frequency, with nearly half of patients at higher doses achieving a 50% or more reduction, while topiramate demonstrated effectiveness in reducing migraine frequency in two separate trials, with some patients even experiencing weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic drugs in migraine prevention. Mathew, NT.[2019]

Antidepressants, particularly tricyclics, can be beneficial in treating both migraine and depression, but often a single antidepressant is not enough to effectively manage both conditions, necessitating combination therapies.

The review highlights the importance of understanding the interactions between various medications, including antidepressants and migraine prophylactics, to ensure effective treatment while minimizing the risk of adverse interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressants in long-term migraine prevention. Koch, HJ., Jürgens, TP.[2018]

Preventive pharmacological treatments for migraines, such as amitriptyline, divalproex, topiramate, and beta-adrenergic blockers (like propranolol), have strong evidence supporting their efficacy, based on clinical experience and level I evidence.

While these medications can be effective, they also come with varying degrees of side effects that may limit their use, highlighting the importance of balancing treatment efficacy with safety and patient preferences in migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic pharmacotherapy for migraine headaches. Buchanan, TM., Ramadan, NM.[2006]

In a pilot study involving up to 20 patients per treatment group over 12 weeks, high-dose cyclobenzaprine (30 mg) significantly reduced tinnitus symptoms as measured by the Tinnitus Handicap Inventory (THI) score.

Other muscle relaxants tested, including orphenadrine, tizanidine, and eperisone, did not show effectiveness, suggesting that cyclobenzaprine may be a promising new treatment for tinnitus that requires further validation in controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study. Coelho, C., Figueiredo, R., Frank, E., et al.[2014]

Preventive therapy for migraines is recommended for adults experiencing more than 6 headache days per month, with options including FDA-approved medications like propranolol, topiramate, and onabotulinumtoxinA, as well as effective off-label drugs such as lisinopril and amitriptyline.

The response to preventive treatments varies widely among individuals, with complete cessation of headaches being rare, but some patients experience significant relief, highlighting the importance of personalized treatment plans and gradual dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018. Loder, E., Rizzoli, P.[2019]

Migraine prophylaxis involves various drug classes, including antidepressants, beta-blockers, and antiepileptics, which work by normalizing neuronal excitability and blocking pain pathways, thus reducing the frequency and intensity of migraine attacks.

Recent trials have shown promising results for new treatments like angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, expanding the options available for migraine prevention beyond traditional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathophysiological basis of migraine prophylaxis. Galletti, F., Cupini, LM., Corbelli, I., et al.[2009]

Migraine preventive drugs, such as amitriptyline, topiramate, and beta-blockers, are effective first-line treatments, with their mechanisms primarily focusing on inhibiting cortical excitation and restoring nociceptive dysmodulation.

While these drugs can be effective, they also come with varying degrees of adverse effects, highlighting the importance of balancing efficacy with safety and patient preferences in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current trends in migraine prophylaxis. Ramadan, NM.[2009]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Antiepileptic drugs in migraine prevention. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Antidepressants in long-term migraine prevention. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Prophylactic pharmacotherapy for migraine headaches. [2006]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Pathophysiological basis of migraine prophylaxis. [2009]

7. United States pubmed.ncbi.nlm.nih.gov

Current trends in migraine prophylaxis. [2009]