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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Vestibular migraine (VM) is one of the most common causes of vertigo attacks, affecting 1 - 5% of people. People with vestibular migraine have lower quality of life compared to others and some may experience completely debilitating symptoms. Symptoms include vertigo, nausea, head motion-induced dizziness, unsteadiness, balance problems, and lightheadedness. There is evidence the medication amitriptyline in isolation and also our lifestyle modification intervention in isolation can each help reduce symptoms of dizziness and headache in patients with VM. However, these data are observational and subject to various types of bias. The purpose of the current investigation is to determine outcomes from each intervention using randomized allocation of participants diagnosed with VM into either the amitriptyline arm or the lifestyle modification arm. The investigators will measure for change in dizziness using the Dizziness Handicap Inventory (DHI) and for change in headache using the Headache Disability Inventory (HDI). For participants in the lifestyle modification arm, the investigators will also measure for change in lifestyle factor to determine improvement on those intervention factors. Measures will be obtained pre-intervention to establish baseline, at 30 days, 60 days, and 90 days. the investigators will also re-survey participants one year after initiation of intervention to determine adherence and status.

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 amitriptyline safe for humans?

Amitriptyline can cause side effects like drowsiness, difficulty concentrating, and low blood pressure when standing up. It may also lead to high blood pressure in some cases, so regular monitoring is recommended. ^{1 2 3 4 5}

How does the drug amitriptyline differ from other migraine treatments?

Amitriptyline is unique because it is primarily used as a preventive treatment for migraines, rather than for immediate relief, and it works by affecting neurotransmitters (chemical messengers in the brain) like serotonin and norepinephrine. Unlike some other migraine treatments that target specific receptors for quick relief, amitriptyline is a tricyclic antidepressant that helps reduce the frequency of migraines over time. ^{4 5 6 7 8}

Research Team

Richard A Roberts, PhD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

Group I: Lifestyle Modification Active Control 1 Intervention

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+

Findings from Research

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. [2022]

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

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

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

Hypertension Secondary to Amitriptyline Use as Prophylactic for Migraine in a 26-Year-Old Man. [2021]

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

Amitriptyline in the prophylactic treatment of migraine and chronic daily headache. [2022]

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

Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial. [2014]

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

Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels. [2022]

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

Classics in Chemical Neuroscience: Amitriptyline. [2022]

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

Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications. [2019]