Amitriptyline for Migraine

(RCTVM Trial)

Overseen By Richard A Roberts, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: MAO inhibitors, SSRIs

Disqualifiers: Meniere's, Pregnancy, Stroke, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how well amitriptyline and lifestyle changes help individuals with vestibular migraine, a condition causing dizziness and headaches. Participants will join one of two groups: one group will take amitriptyline, a medication, while the other will follow lifestyle advice, such as improving sleep and exercise, for three months. The trial seeks individuals already diagnosed with vestibular migraine and using medication for migraine attacks. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to the foundational understanding of managing vestibular migraines.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow for the use of rescue medication for migraines. However, if you are using an MAO inhibitor or an SSRI antidepressant, you may need to stop those before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amitriptyline can reduce the number of migraine days. However, it may cause side effects such as nausea, constipation, and drowsiness. Some individuals may also experience dizziness or lightheadedness upon standing, known as orthostatic hypotension.

More serious risks exist as well. Amitriptyline can increase the risk of suicidal thoughts and behaviors, so it is crucial to consider this carefully and discuss it with a healthcare provider.

Although amitriptyline has been used for migraines before, this study is in the early stages. The primary goal is to assess how well participants tolerate the treatment. If there are any concerns, consulting a doctor before starting any new medication is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about amitriptyline for migraines because it offers a different approach compared to the standard options like triptans, beta-blockers, and CGRP inhibitors. Amitriptyline, originally an antidepressant, works by affecting neurotransmitters in the brain, which can help prevent migraines. Additionally, the lifestyle modification arm of this trial emphasizes holistic strategies such as improving sleep, regularizing meals, avoiding dietary triggers, and incorporating exercise, which could complement medication and offer a more comprehensive treatment plan for migraine sufferers. This dual approach not only targets the biological aspect but also encourages lifestyle changes that might enhance overall well-being.

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

This trial will compare amitriptyline with lifestyle modification for migraine management. Research has shown that amitriptyline can help reduce migraine symptoms. In one study, about 80% of patients felt better after using amitriptyline. This medication lowered the number of migraine attacks each month, from around 11 to 3 on average. While it may not be the strongest option compared to newer treatments, it has a history of helping many people manage their symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Richard A Roberts, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals who experience vestibular migraine, which includes symptoms like vertigo, nausea, and balance issues. Participants must be diagnosed with VM to join the study. The trial will involve a random assignment to either take the medication Amitriptyline or engage in lifestyle modifications.

Inclusion Criteria

I have been diagnosed with vestibular migraine.

I am currently taking medication for sudden migraine attacks.

Exclusion Criteria

Contraindicated for intervention with amitriptyline including: Patients with Hepatic Impairment, Patients with Renal Impairment, Pregnancy, Breastfeeding, Elderly Patients, Allergy to amitriptyline, Heart attack, Used an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazide, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others, Used an 'SSRI' antidepressant in the past 5 weeks, such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone, Bipolar disorder (manic-depression) or schizophrenia, Mental illness or psychosis; Stroke, Seizures, Diabetes (amitriptyline may raise or lower blood sugar); Glaucoma, Problems with urination

I am currently taking amitriptyline.

I am currently being treated for Meniere's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into either the amitriptyline arm or the lifestyle modification arm for 90 days

12 weeks

Visits at baseline, 30, 60, and 90 days

Follow-up

Participants are monitored for adherence and status one year after initiation of intervention

1 year

1 visit (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Amitriptyline

Trial Overview

The study aims to compare the effectiveness of Amitriptyline against lifestyle changes in reducing dizziness and headache symptoms associated with vestibular migraine. Progress will be tracked using specific inventories for dizziness (DHI) and headaches (HDI), at intervals up to one year.

How Is the Trial Designed?

Group I: Lifestyle Modification Active Control 2 Interventions

Written and video instructions to help improve restful sleep, mealtime regularity, avoidance of dietary triggers, and exercise for 90 days.

Group II: Amitriptyline Active Control 1 Intervention

amitriptyline, tablet, 25 mg, once daily, 90 days

Amitriptyline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Elavil for:

• Depression
• Anxiety and Stress
• Chronic Pain
• Fibromyalgia
• Headache
• Migraine Prevention
• Neuropathic Pain

Approved in European Union as Amitriptyline for:

• Depression
• Anxiety disorders
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Approved in Canada as Elavil for:

• Depression
• Anxiety and stress
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

In a study of 274 adolescent patients aged 12-17, eletriptan 40 mg did not show a significant difference in immediate 2-hour headache response compared to placebo (57% for both), indicating that its acute efficacy may be limited in this age group.

However, eletriptan demonstrated a significant reduction in headache recurrence within 24 hours (11% for eletriptan vs 25% for placebo) and better sustained headache response rates, suggesting it may be beneficial for longer-term management of migraines in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial. Winner, P., Linder, SL., Lipton, RB., et al.[2014]

In a double-blind study involving 64 migraine patients, amitriptyline significantly reduced headache attacks but caused severe drowsiness in many participants, indicating a notable side effect.

Fluvoxamine also effectively reduced the frequency of migraine attacks with only mild side effects, suggesting it could be a safer alternative for migraine prophylaxis compared to amitriptyline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of amitriptyline and fluvoxamine in migraine prophylaxis. Bánk, J.[2019]

Eletriptan shows a higher selectivity for contracting the middle meningeal artery compared to the coronary artery, indicating a lower risk of adverse coronary side effects at therapeutic doses, which is important for migraine treatment.

Both eletriptan and sumatriptan have similar efficacy in contracting the middle meningeal artery, but eletriptan is less potent in the coronary artery, suggesting it may be safer for patients without coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels. MaassenVanDenBrink, A., van den Broek, RW., de Vries, R., et al.[2022]

Amitriptyline, introduced in 1961 as Elavil, is an effective treatment for major depressive disorder, working by inhibiting the reuptake of serotonin and norepinephrine, which helps in managing mood disorders.

Despite its therapeutic benefits, amitriptyline poses a risk of cardiotoxicity due to its off-target effects on various receptors, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classics in Chemical Neuroscience: Amitriptyline. McClure, EW., Daniels, RN.[2022]

In a study of 52 patients with migraines, both amitriptyline (AMT) and venlafaxine (VLF) significantly reduced pain, but AMT caused more intolerable side effects, leading to higher dropout rates.

Venlafaxine was associated with fewer side effects compared to amitriptyline, suggesting it may be a safer option for migraine prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Bulut, S., Berilgen, MS., Baran, A., et al.[2022]

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