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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether migraine medications can reduce the impact of tinnitus, the perception of ringing or noise in the ears without external sound. The study tests two medication combinations: one group takes verapamil (a calcium channel blocker) and paroxetine (an antidepressant), while another group takes nortriptyline (an antidepressant) and topiramate (an anticonvulsant). Researchers will measure participants' tinnitus symptoms before and after treatment to assess improvement. Ideal candidates for this trial have mild to moderate tinnitus and can commit to taking medication and attending study visits. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

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.

What is the safety track record for these treatments?

Research shows that combinations of verapamil with paroxetine and nortriptyline with topiramate are generally well-tolerated. Studies have found that these combinations can reduce tinnitus severity for many patients with relatively few side effects.

When used at moderate doses, about 40% to 50% of patients experienced improvements in tinnitus symptoms without significant negative effects. This suggests that these medications are generally safe. However, larger studies are needed to confirm these results over a longer period.

In this trial, researchers start verapamil and paroxetine at low doses and gradually increase them based on patient response. The same method applies to nortriptyline and topiramate. This gradual increase helps manage any possible side effects.

These medications are already used for other conditions, such as migraines and depression, which provides some confidence about their safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for tinnitus because they repurpose migraine medications, which is a novel approach. Unlike traditional tinnitus treatments that often focus on sound therapy or cognitive behavioral therapy, these drugs—Nortriptyline, Paroxetine, Topiramate, and Verapamil—work by targeting neurological pathways that could be linked to both migraines and tinnitus. This could offer a new way to manage tinnitus symptoms, especially for individuals who haven't found relief with existing options. Additionally, the ability to adjust dosages based on symptom improvement provides a personalized treatment approach, potentially enhancing effectiveness and minimizing side effects.

What evidence suggests that this trial's treatments could be effective for tinnitus?

In this trial, participants will be assigned to one of two treatment groups. Studies have shown that the Verapamil-Paroxetine combination, one of the treatment options, can effectively reduce tinnitus severity in about 40-50% of patients. Similarly, the Nortriptyline-Topiramate combination, another treatment option, has demonstrated comparable effectiveness. Researchers measured this improvement using the Tinnitus Functional Index (TFI), which tracks changes in tinnitus symptoms. Both drug combinations have shown promise in trials, significantly reducing tinnitus severity compared to a placebo. These treatments are generally well-tolerated and have fewer side effects at moderate doses. However, experts suggest that more extensive studies are needed to confirm these findings over longer periods. ^{1 2 3 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

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

I am between 25 and 85 years old.

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

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39588680/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0ta0Q3IXt1voohclJGj-6RlAP-94WkWif6eMSAAYb_D&fc=None&ff=20241127232155&v=2.18.0.post9+e462414

Efficacy of Nortriptyline-Topiramate and Verapamil-Paroxetine ... Both combinations of drugs were promising in improving tinnitus severity. However, larger-scale trials with longer follow-up periods are warranted.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/lary.32338?af=R

Optimal Dosing of Nortriptyline–Topiramate and Verapamil ... Both NT and VP combinations at moderate doses effectively reduce tinnitus severity in approximately 40% of patients, with fewer adverse effects ...

3. medschool.uci.edu medschool.uci.edu/news/neurotology-faculty-pioneers-placebo-controlled-trial-tinnitus

Neurotology Faculty Pioneers Placebo-controlled Trial For ... Both drug combinations resulted in a significant decrease in tinnitus severity captured by the TFI scores, which was not observed in the placebo ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40515518/

Optimal Dosing of Nortriptyline-Topiramate and Verapamil ... Both NT and VP regimens effectively reduce tinnitus severity in approximately half of the patients at moderate doses within 8 weeks.

5. escholarship.org escholarship.org/content/qt5tm6633k/qt5tm6633k.pdf

Efficacy of Nortriptyline‐Topiramate and Verapamil‐ ... To evaluate the efficacy of 2 drug combinations on tinnitus severity and associated stress, depression, sleep, and anxiety. Study Design. A ...

6. withpower.com withpower.com/trial/phase-4-tinnitus-8-2019-acbde

Migraine Medications for Tinnitus Research has shown that combining nortriptyline with topiramate or verapamil with paroxetine can be safe for people with tinnitus. Studies have found that these ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04404439?term=AREA%5BConditionSearch%5D(%22Tinnitus%22)&rank=10

Treatment of Tinnitus With Migraine Medications Nortriptyline may be increased by 7.5mg weekly (to a maximum of 60mg), topiramate by 10mg weekly (maximum 80mg), verapamil by 30mg weekly (maximum 240mg), and ...