New Headache and Migraine Treatments On the Horizon

By Anisa Kelley, MD, Associate Director of Lurie Children's Headache Program 

Migraine headaches can be troublesome and debilitating, especially among children and adolescents that experience them. A migraine is a headache often accompanied by other symptoms such as:

• Nausea
• Vomiting
• Light sensitivity
• Sound sensitivity
• Fatigue 
• Dizziness

When a person is experiencing a migraine, it’s important to find an appropriate and individualized treatment plan, in both prophylactic measures (medications or lifestyle changes implemented to prevent the onset of migraine) and abortive/acute measures (medications used to treat a migraine attack when it occurs).

More than just reducing the pain and unpleasantness associated with migraine attacks, treating migraines is important because we know that “migraines beget more migraines.” What this means is, if you do not treat a migraine adequately when you experience one, your brain and pain pathways will be primed to making you susceptible to more migraine attacks. Although most new migraine treatments focus on the adult population, many of those same treatments are being studied for use in adolescent and pediatric populations.

Below we discuss some current migraine treatments as well as new migraine treatments on the horizon for children and adolescents.

Triptans and Nonsteroidal Anti Inflammatory Drugs

The most common and widely used abortive therapies for pediatric migraine include over-the-counter acetaminophen or Non-steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen or naproxen. These medications are safe and effective when used at adequate doses to treat migraine attacks and are an excellent first option. As with all acute treatment options, it’s important not to use NSAIDs or acetaminophen more than two times a week consistently, as this can cause medication overuse headache.

Triptan medications (serotonin receptor agonists) are another common therapy used to acutely treat migraines. Whereas NSAIDs and acetaminophen treat general pain throughout the body, triptan medications are more targeted toward treating migraine evolution in the brain. Triptans that are approved in the pediatric and adolescent population include sumatriptan, rizatriptan, zolmitriptan, and almotriptan. These medications are generally safe and well tolerated. Common side effects include fatigue and tingling. These medications are available in tablet, disintegrating tablet, nasal and injectable formulations.

Superficial Nerve Blocks

Superficial nerve blocks are skin-level injections of anesthetic (which are numbing medication like lidocaine), sometimes with steroids, around nerves that propagate headache pain. By numbing certain nerves, headache pain signaling pathways are modulated and “calmed down”. The duration of headache benefit can last from hours to months⁶. Although the published literature for superficial nerve block in children is limited, the majority of pediatric headache specialists perform these nerve blocks in the same proportion used among adult headache populations⁶. Patients who may benefit from these may have chronic migraine, status migrainosis, or neuralgia of the occipital or trigeminal nerves.

At the Headache Procedure Clinic at Lurie Children’s, we offer supraorbital nerve blocks, occipital nerve blocks, sphenopalatine ganglion blocks and trigger point injections. These are available to certain patients for whom providers feel would be good candidates for the procedure and would likely experience benefit.

Cognitive Behavioral Therapy (CBT)

Mental health concerns, stress and pain coping mechanisms are huge components of pediatric migraine propagation and treatment.

Nonpharmacological treatments like cognitive behavioral therapy (CBT), meditation and yoga are some techniques aimed at addressing mental health and improving body awareness. Ultimately these techniques can aid in successful treatment of migraine. CBT strategies for headache can include education on the pain systems, deep breathing, progressive muscle relaxation, guided imagery, activity pacing, cognitive modifications, distraction and cued relaxations⁴. CBT has demonstrated effectiveness in pediatric migraine, and is an excellent accompaniment to pharmacological measures for pediatric migraine treatment.

Neuromodulation 

Neuromodulation is non-pharmacological treatment option for pediatric migraine, in which noninvasive devices provide a nerve stimulation that inhibits or modulates pain mechanisms. One device is called Nerivivo®, or remote electrical neuromodulation (REN). The REN device is a wireless, wearable,  battery operated stimulation unit applied to the lateral upper arm. The device stimulated small skin nerves in the upper arm during a migraine attack, effectively stopping the migraine headache pain in its tracks. In an adolescent study for the REN device, the device was found to be safe, well-tolerated and up to 72% of participants experienced pain relief at two hours post onset of migraine².

Another neuromodulation device is the Cefaly device, an External Trigeminal Nerve Stimulation device (e-TNS). The device is worn on the forehead, and provides stimulation to the trigeminal nerve. Although approved for 18 and older, it can be trialed in adolescents for acute or prophylactic migraine treatment.

Calcitonin-gene Related Peptide (CGRP) Inhibiters

CGRP inhibitors have been FDA approved for treatment of intractable migraines in adults for the past few years, during which time they have revolutionized migraine treatment in adults. CGRP inhibitors come in both prophylactic and acute treatments options. When used as prophylactic treatments (either a once-a-month self-administered injection or daily medication), migraine attacks are often reduced up to 50% or more in the adult population⁵. Pediatric and adolescent migraine trials are underway.

Anecdotally, many pediatric and adolescent patients are finding this class of medications to be effective and tolerable. But, unfortunately, outcome data from these trials are still unlikely to be available for a couple of years. Current CGRP medications being trialed in pediatric populations include erunumab (Aimovig®), eptinezumab (Vyepti ®), fremanezumab (Ajovy®), galcanezumab (Emgality®), ubrogepant (Ubrelvy®) and rimegepant (Nurtec®)³. In cases of intractable chronic migraine, some providers may choose to try CGRP inhibitors off-label in certain pediatric patients cautiously, mostly in post-pubertal adolescents⁷.

Onabotulinum Toxin A (Botox) Injections

In adults with chronic migraine (more than 15 headaches days per month for three months), Botox injections have been proven to be effective in reducing migraine headache days. Botox therapy is a series of 31 superficial injections around the head and neck completed every three months. These injections provide muscle relaxation, and inhibit pain receptors in trigeminovascular neurons.

In a 2019 study of 30 adolescents, headaches days were reduced from an average of 24 headache days to 15 headache days Post-Botox, and the headaches themselves were less severe post-Botox¹. Botox is not yet approved in adolescent populations. However in some cases of intractable, chronic migraines, providers may choose to try the treatment off-label in adolescent populations if available.

Conclusion

Overall this is a very exciting time for pediatric headache and migraine management. We can look forward to new clinical trials and new medications in the next few years. Lurie Children's Headache Program is dedicated to providing patients with the best, individualized treatment plans available to provide headache relief.

Learn more about the Headache Program

Works Cited

1. Ali SS, Bragin I, Rende E, Mejico L, Werner KE. Further Evidence that Onabotulinum Toxin is a Viable Treatment Option for Pediatric Chronic Migraine Patients. Cureus. 2019 Mar 29;11(3):e4343. doi: 10.7759/cureus.4343. PMID: 31187008; PMCID: PMC6541167.
   
   
2. Hershey AD, Lin T, Gruper Y, Harris D, Ironi A, Berk T, Szperka CL, Berenson F. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021 Feb;61(2):310-317. doi: 10.1111/head.14042. Epub 2020 Dec 21. PMID: 33349920.
   
   
3. Iannone LF, De Cesaris F, Geppetti P. Emerging Pharmacological Treatments for Migraine in the Pediatric Population. Life (Basel). 2022 Apr 5;12(4):536. doi: 10.3390/life12040536. PMID: 35455026; PMCID: PMC9031827.
   
   
4. Kroon Van Diest AM, Powers SW. Cognitive Behavioral Therapy for Pediatric Headache and Migraine: Why to Prescribe and What New Research Is Critical for Advancing Integrated Biobehavioral Care. Headache. 2019 Feb;59(2):289-297. doi: 10.1111/head.13438. Epub 2018 Nov 16. PMID: 30444269; PMCID: PMC6351174.
   
   
5. Goadsby PJ, Paemeleire K, Broessner G, Brandes J, Klatt J, Zhang F, Picard H, Lenz R, Mikol DD. Efficacy and safety of erenumab (AMG334) in episodic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia. 2019 Jun;39(7):817-826. doi: 10.1177/0333102419835459. Epub 2019 Apr 13. PMID: 30982348.
   
   
6. Szperka CL, Gelfand AA, Hershey AD. Patterns of Use of Peripheral Nerve Blocks and Trigger Point Injections for Pediatric Headache: Results of a Survey of the American Headache Society Pediatric and Adolescent Section. Headache. 2016 Nov;56(10):1597-1607. doi: 10.1111/head.12939. Epub 2016 Oct 12. PMID: 27731894; PMCID: PMC5830113.
   
   
7. Szperka CL, VanderPluym J, Orr SL, Oakley CB, Qubty W, Patniyot I, Lagman-Bartolome AM, Morris C, Gautreaux J, Victorio MC, Hagler S, Narula S, Candee MS, Cleves-Bayon C, Rao R, Fryer RH, Bicknese AR, Yonker M, Hershey AD, Powers SW, Goadsby PJ, Gelfand AA. Recommendations on the Use of Anti-CGRP Monoclonal Antibodies in Children and Adolescents. Headache. 2018 Nov;58(10):1658-1669. doi: 10.1111/head.13414. Epub 2018 Oct 15. PMID: 30324723; PMCID: PMC6258331.

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