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Medications

Information provided about medications is to assist in understanding and discussing these options with a doctor and to supplement information provided by a doctor or healthcare professional. If you have concerns, want to learn more about a medication or want to change your child or teen’s medications please, talk to your doctor.

Angiotensin II receptor blockers (ARBs)

 

Names: Losartan, olmesartan, telmisartan, valsartan, candesartan

 

How angiotensin II blockers work: The exact mechanism of how ARBs work to prevent migraines is unknown. 1 ARBs similar calcium channel blockers, reduce blood pressure, which impacts blood flow through vessels. The exact mechanism of ARBs and calcium channel blockers are different.

 

Evidence in children: Studies investigating ARBs in adults have shown promising results 2 In children there is less evidence but one drug, candesartan, is possibly effective.  3

 

Cautions: Studies with candesartan found that the side effects for candesartan were comparable to the side effects of placebo. 4

Anticonvulsants/anti-epileptic drugs

 

Names:  Valproate, topiramate, valproic acid, gabapentin, levetiracetam

 

How anti-convulsants work: Anti-convulsants work by blocking cellular actions that would activate a nerve cell (neuron). Anticonvulsants, therefore, prevent neurons in the brain from working unnecessarily and being too active.

 

Evidence in children: Topiramate is the only FDA approved preventative therapy for children with migraines. 5 Valproic acid is a medication that has been shown to work well, particularly for young children. Topiramate, gabapentin and levetiracetam have all been shown to reduce the number of headache days’ children and adolescents with migraine have. 6 Although topiramate is one of the most used migraine medications for children there are also some studies that show it is about as effective as a placebo. 7 This doesn’t mean that there are no benefits to taking topiramate just that there are other options that should be explored first.

 

Cautions: Although anticonvulsants are generally a good option for preventing migraines in children they can have side effects. Some of the side effects can be weight gain or weight loss, hair loss, stomach pain, sleepiness, or mental fogginess. Valproic acid should be avoided in women (including teenage women) who are pregnant or considering becoming pregnant. 6

Antihistamines

 

Names: Cyproheptadine

 

How antihistamines work: Cyprohepatadine works in two ways. One of the ways it works is through the same pathways that SSRIs act on, by enhancing the body’s pain control mechanisms; it also works in the way that calcium channel blockers work, by preventing the blood vessels from overly-constricting in the brain.

 

Evidence in children: Using propranolol (a beta-blocker) and cyrproheptadine together has been demonstrated to be one of the more effective therapies available to children. 6

 

Cautions: Cyproheptadine is often given at bedtime to avoid daytime sleepiness. Some children experience increased appetite and weight gain.

Beta-blockers

 

Names: Propranolol (Inderal, Inderal LA), timolol (Blocadren), metoprolol

 

How beta-blockers work: Beta-blockers block the relay of information between certain nerves. This can limit ‘central sensitization’. Central sensitization happens in chronic pain conditions, like migraine, where the brain is in a state of high reactivity and when a person encounters normal, everyday things the result is they feel pain or more pain than they normally would. 8

 

Evidence in children: In children, evidence for the use of beta-blockers alone is limited. Although beta-blockers are a mainstay therapy for adults, generally they do not seem to be as effective at preventing migraines in children. One study found when children took beta-blockers they had fewer migraine symptoms but two other studies did not find beta-blockers helped children with migraines. 9 Propranolol taken with cyproheptadine (an antihistamine) has a lot of evidence as being one of the most effective therapies for children. 6

 

Cautions: If a child has asthma or diabetes beta-blockers are not considered an appropriate medication.  Beta-blockers can also cause or aggravate depression. 9

Calcium channel blockers

 

Names: Cinnarizine, flunarizine, nfedipine, verapril, diltiazem

 

How calcium channel blockers work: How calcium channel blockers work to prevent migraine is generally not known. Previous theories of migraine said that migraines were caused by the constriction and then dilation of the brain’s vascular system. Calcium channel blockers are typically used to treat high blood pressure because they act on the muscles of the heart to slow the heart’s contractions. The downstream effect of reducing the amount of work the heart is doing is that the blood vessels relax and widen.

 

Evidence in children: Calcium channel blockers are generally not recommended for preventing migraines in children, as there has been inadequate support demonstrating that these medications are beneficial. There are still two studies, however, that found that calcium channel blockers reduced the number of headache days and the headache pain in children with migraine. 6

 

Cautions: Calcium channel blockers may cause weight gain. Calcium channel blockers should not be taken with grapefruits or grapefruit juice, as grapefruits affect the way the body breaks down and clears this drug.

CGRP (calcitonin gene-related peptide) blockers

 

Names: Fremanezumab

 

How CGRP blockers work: Calcitonin gene-related peptide (CGRP) is a molecule called a peptide. Peptides are smaller proteins that can act as signals, as they do in migraine. CGRP is overly expressed in people with migraine, meaning they have more of this peptide than other people did.  CGRP is theorized to be one of the signals, which eventually causes irritation of the protective layers of the brain. 10 CGRP blockers prevent the action of CGRP and therefore prevent the pain.

 

Evidence in children: This drug has recently been released as the first drug that is specifically targeted to reduce migraines but it currently has not been tested in children with migraines. There are plans in the near future to do a study to measure whether the drug works in 12-18-year-olds and to see what the side effects are in people of this age. 11

 

Cautions: This medication has not yet been tested with children.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Names: Fluoxetine

How SSRIs work: SSRIs work in a similar way to tricyclic antidepressants; they work by increasing the body’s own pain control mechanisms.

Evidence in children: There is no evidence that SSRIs are effective in children, although there is good evidence that they work in adults. 9 Older teenagers who get migraines that are more similar to migraines in adults (same location, duration, and describing words) may get an SSRI that would work for them. 4

Cautions: A person taking SSRIs may feel anxious or nervous, or sometimes may feel dizzy, or lightheaded or feel like vomiting. SSRIs may also change a person’s sleep habits, and the person may be unable to sleep or, alternatively, find that they are very sleepy throughout the day.

Tricyclic antidepressants

Names: Amitriptyline

How tricyclic antidepressants work: Tricyclic antidepressants work by increasing the body’s own pain control mechanisms. 8

Evidence in children: Tricyclic antidepressants are another therapy that is useful in adults but has limited evidence in children. Two studies have found that tricyclic antidepressants can help children with migraines. One study saw a reduction in the number of headaches a child has per month. The other study found that children had less migraine symptoms when they were taking a tricyclic antidepressant. 9 Tricyclical antidepressants are also used to treat medication-overuse headaches, which happen when a person takes NSAIDs (ibuprofen, naproxen) or acetaminophen (Tylenol) too often. 6

Cautions: Researchers and doctors recommend an electrocardiogram, also known as an ECG or EKG before beginning treatment. An ECG/EKG is a machine that looks at the electrical activity in the heart. This is done because sometimes this medication can change the way the electric activity that makes a heart pump moves through the heart. 6

1.         Halker, R. B., Starling, A. J., Vargas, B. B. & Schwedt, T. J. ACE and ARB Agents in the Prophylactic Therapy of Migraine-How Effective Are They? Curr. Treat. Options Neurol. 18, 15 (2016).

2.         Disco, C., Maggioni, F. & Zanchin, G. Angiotensin II receptor blockers: a new possible treatment for chronic migraine? Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 36, 1483–1485 (2015).

3.         Hickman, C., Lewis, K. S., Little, R., Rastogi, R. G. & Yonker, M. Prevention for Pediatric and Adolescent Migraine. Headache J. Head Face Pain 55, 1371–1381

4.         Silberstein, S. D. Preventive Migraine Treatment. Contin. Lifelong Learn. Neurol. 21, 973–989 (2015).

5.         FDA. Topamax drug label. (2009). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020505s052,020844s043lbl.pdf. (Accessed: 5th July 2018)

6.         Teleanu, R. I., Vladacenco, O., Teleanu, D. M. & Epure, D. A. Treatment of Pediatric Migraine: a Review. Mædica 11, 136–143 (2016).

7.         Powers, S. W. et al. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N. Engl. J. Med. 376, 115–124 (2017).

8.         Sprenger, T., Viana, M. & Tassorelli, C. Current Prophylactic Medications for Migraine and Their Potential Mechanisms of Action. Neurotherapeutics 15, 313–323 (2018).

9.         Friedman, G. Advances in paediatric migraine. Paediatr. Child Health 7, 239–244 (2002).

10.       Durham, P. L. & Vause, C. V. CGRP Receptor Antagonists in the Treatment of Migraine. CNS Drugs 24, 539–548 (2010).

11.       Loder, E. W. & Robbins, M. S. Monoclonal Antibodies for Migraine Prevention: Progress, but Not a Panacea. JAMA 319, 1985–1987 (2018).