CBT + Amitriptyline for Childhood Migraine

Recruiting at 13 trial locations

Overseen By Megan Pfeiffer

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Amitriptyline

Must not be taking: Botox, CGRP antibodies

Disqualifiers: Pregnancy, Suicidal thoughts, Bipolar, others

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

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Cognitive Behavioral Therapy (CBT) with and without the antidepressant amitriptyline in preventing migraines in children. It aims to identify the best migraine management approach by comparing telehealth-delivered CBT alone to CBT combined with the medication. The trial is open to children who have migraines with or without aura, experience four or more headaches a month, and can safely take amitriptyline. As an unphased trial, it offers a unique opportunity for children to access innovative migraine management strategies.

Will I have to stop taking my current medications?

The trial requires that you stop taking any current preventive antimigraine medications before starting, as well as amitriptyline or CBT specific to headache care. If you're on other migraine prevention treatments like Botox or CGRP-based medications, you would also need to stop those.

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

Past studies have shown that Cognitive Behavioral Therapy (CBT) is a safe and effective way to treat migraines in children. It is recommended as a first choice for prevention due to its safety.

In contrast, the medication amitriptyline, often used to prevent migraines, has shown mixed results in children. Research indicates it can cause more unwanted side effects compared to other treatments. Some side effects include an increased risk of suicidal thoughts when starting the medication, and it is not approved for children under 12.

When considering joining a trial, these findings are important. CBT is generally well-tolerated, while amitriptyline carries some risks, especially for younger children. Always consult a healthcare provider to determine the best option for you or your child. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for childhood migraine because they combine cognitive behavioral therapy (CBT) with or without amitriptyline, offering a unique approach compared to standard options like over-the-counter pain relievers, triptans, and preventive medications. CBT provides a mind-body approach that includes strategies like muscle relaxation and problem-solving, which can empower children to manage their migraines proactively. When combined with amitriptyline, a well-known migraine prevention medication, this method could enhance effectiveness by addressing both the psychological and physical aspects of migraines. This dual approach has the potential to offer more comprehensive relief and improve the quality of life for young patients.

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

This trial will compare the effectiveness of Cognitive Behavioral Therapy (CBT) alone and in combination with Amitriptyline for treating childhood migraines. Research has shown that CBT works well for treating headaches in children and teens, including migraines. Several studies have proven that CBT greatly reduces both the number of headache days and their severity. More than 70% of children and teens using CBT reported their headaches occurred at least 50% less often.

In contrast, studies on the use of amitriptyline for childhood migraines have not shown it to be more effective than a placebo (a sugar pill with no active medicine). Although it is used, amitriptyline doesn't consistently reduce the frequency of headaches or their impact on daily life for children. Therefore, while strong evidence supports CBT's effectiveness for migraines in young people, amitriptyline lacks strong support for making a significant difference in this age group. ^{1 4 5 6 7}

Who Is on the Research Team?

Scott Powers, PhD

Principal Investigator

Cincinnati Childrens Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for young people who have migraines at least 4 days a month and meet specific migraine criteria. They must be able to speak English, not be pregnant, and can't currently be on certain migraine medications like Botox or CGRP antibodies. They also shouldn't have taken amitriptyline or had CBT for headaches recently, nor should they have serious mental health issues.

Inclusion Criteria

I am approved to take amitriptyline for preventing migraines.

I've had 4 or more headache days in the last 28 days.

I have been diagnosed with migraines, following international headache guidelines.

Exclusion Criteria

Any and all other diagnoses or conditions which, in the opinion of the site investigator, would prevent the patient from being a suitable candidate for the study or interfere with the medical care needs of the participant

I am currently being treated with amitriptyline or undergoing cognitive behavioral therapy for headaches.

I am currently taking medication to prevent migraines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo a baseline period to establish initial headache frequency and severity

4 weeks

Treatment

Participants receive six telehealth CBT sessions over 8 weeks, with dose titration of amitriptyline for the CBT + medication group

8 weeks

6 telehealth sessions

Maintenance

Participants maintain the dose of medication and attend booster CBT sessions three times over 4 months

16 weeks

3 booster sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amitriptyline
• CBT

Trial Overview The study tests if Cognitive Behavioral Therapy (CBT) via telehealth combined with the medication amitriptyline is more effective than just CBT via telehealth in preventing migraines in youth. Participants will either receive both treatments or only CBT to see which works better.

How Is the Trial Designed?

Group I: CBT while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline) Experimental Treatment 2 Interventions

This intervention consists of Cognitive Behavioral (CBT), a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation, activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements. This arm will also take a daily oral dose of Amitriptyline, which will be clinically prescribed and managed by the patient's headache provider.

Group II: CBT alone Experimental Treatment 1 Intervention

This intervention arm consists of 6 Cognitive Behavioral Therapy (CBT), a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation, activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements.

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?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

In a study of 135 children and adolescents with chronic migraines, those who received cognitive behavioral therapy (CBT) along with amitriptyline showed a significantly greater reduction in headache frequency compared to those who received headache education and amitriptyline, with 47% achieving ≤4 headache days per month at 20 weeks versus 20% in the education group.

At the 12-month follow-up, 72% of the CBT plus amitriptyline group maintained ≤4 headache days per month, indicating that combining CBT with medication not only provides immediate benefits but also supports long-term management of chronic migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to ≤4 Per Month. Kroner, JW., Hershey, AD., Kashikar-Zuck, SM., et al.[2023]

In a study of 135 patients aged 10-17 with chronic migraines, those receiving cognitive-behavioral therapy (CBT) combined with amitriptyline (CBT+A) experienced a significantly greater reduction in headache days compared to those receiving headache education (HE) with amitriptyline (HE+A).

The CBT+A group showed faster improvement, with a higher percentage achieving a ≥50% reduction in headache days each month, indicating that CBT enhances the efficacy of amitriptyline in treating chronic migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trajectory of Improvement in Children and Adolescents With Chronic Migraine: Results From the Cognitive-Behavioral Therapy and Amitriptyline Trial. Kroner, JW., Peugh, J., Kashikar-Zuck, SM., et al.[2019]

In a study of 118 pediatric patients with severe migraines, combining nonpharmacologic measures with low-dose propranolol or amitriptyline resulted in over 80% of patients experiencing a reduction in headache frequency by more than 50%.

Propranolol was found to be more effective for patients without aura and is preferred over amitriptyline due to its lower risk of side effects, making it a safer option for treating migraines in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpharmacologic treatment of migraine with low-dose propranolol or amitriptyline. Eidlitz-Markus, T., Dlugatch, Y., Haimi-Cohen, Y., et al.[2013]

Acute treatment options for pediatric migraines, such as ibuprofen, acetaminophen, and nasal sprays of sumatriptan and zolmitriptan, have been shown to be both safe and effective in controlled trials.

For preventive treatment, flunarizine has the best efficacy profile, although it is not available in the U.S., while other medications like topiramate and amitriptyline are being explored for their effectiveness in reducing migraine frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacological treatment options for pediatric migraine: an evidence-based appraisal. Lewis, DW., Winner, P.[2018]

There are currently no well-controlled clinical trials demonstrating the effectiveness of any specific medication for preventing migraine headaches in children, highlighting a gap in research.

Open-label studies suggest that amitriptyline and divalproex sodium may be effective for migraine prevention, potentially working through mechanisms involving 5-HT2 receptor antagonism or ion channel regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive therapy in pediatric migraine. Wasiewski, WW.[2017]

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 57 children aged 9-16 with chronic daily headache, both amitriptyline and topiramate showed similar efficacy, with 55% and 61% of patients responding to treatment, respectively, after 4 months.

There were no significant differences in the frequency or severity of headaches between the two medications, indicating that topiramate is as effective and tolerable as amitriptyline for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial comparing amitriptyline versus topiramate for the prophylaxis of chronic daily headache in pediatric patients. Sezer, T., Kandemir, H., Alehan, F.[2018]

Cognitive Behavioral Therapy (CBT) is effective in reducing headache frequency and related disability in children and adolescents, making it a strong candidate for first-line preventive treatment for pediatric headaches and migraines.

Recent studies suggest that traditional medication for headaches may primarily work through a placebo effect, highlighting the importance of integrating non-pharmacological therapies like CBT into treatment plans, which have minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Pediatric Headache and Migraine: Why to Prescribe and What New Research Is Critical for Advancing Integrated Biobehavioral Care. Kroon Van Diest, AM., Powers, SW.[2020]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1610384

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric ... Conclusions. There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7042942/

Efficacy, Safety, and Acceptability of Pharmacologic ... In this network meta-analysis, comparing head-to-head and placebo-controlled trials found no significant long-term effects for migraine prophylaxis relative to ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2824677

Preventive Medications in Pediatric Migraine Adverse events were higher with amitriptyline (RR, 3.81; 95% CI, 1.41-10.32), topiramate (RR, 4.34; 95% CI, 1.60-11.75), and valproate (RR, 5.93 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01581281

The Childhood and Adolescent Migraine Prevention Study The investigators want to see if amitriptyline and/or topiramate are better than placebo (sugar pill) in reducing headache frequency in children and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3637406/

Childhood and Adolescent Migraine Prevention (CHAMP) Study The primary outcome will be a 50% reduction in headache frequency between the 28 day baseline and the final 28 days of treatment (weeks 20–24). Conclusions. The ...

6. drugs.com drugs.com/amitriptyline.html

Amitriptyline Uses, Dosage, Side Effects, Warnings Amitriptyline is not approved for use in pediatric patients less than 12 years of age. You may have thoughts about suicide when you first start ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/amitriptyline-oral-route/description/drg-20072061

Amitriptyline (oral route) - Side effects & dosage Appropriate studies have not been performed on the relationship of age to the effects of amitriptyline in children below 12 years of age. Safety and efficacy ...