Zolmitriptan is one of seven triptans available in the US and it comes in tablets (Zomig), orally disintegrating tablets, that is tablets that melt in your mouth (Zomig ZMT), and nasal spray (Zomig NS). The nasal spray was just approved for children 12 and older. It is available in 2.5 mg and 5 mg strength and the 2.5 mg is the starting dose, but kids are allowed to take 5 mg dose up to twice a day.

My previous post mentioned the approval of Treximet, a combination of sumatriptan (Imitrex) and naproxen (Aleve) in adolescents. However, Zomig is the only triptan in a nasal spray form (the second triptan available in a nasal spray is sumatriptan or Imitrex) approved in the US for children. The advantages of this form of drug delivery is that it tends to have faster onset of action and it can be taken when severe nausea or vomiting precludes the use of oral medications. Sumatriptan nasal spray is approved in kids in Europe, so there is no reason not to use it as well, however Zomig spray seems to be better than Imitrex spray. The amount of fluid in a single dose of Zomig is less than that in Imitrex and the spray droplets are of smaller size, leading to better retention of fluid in nasal passages and better absorption. Also, many patients complain of a very unpleasant taste with Imitrex spray, although this can be avoided by sucking on a hard candy while spraying. This will carry the saliva out of the mouth down the throat and the drug will not reach the mouth. When using nasal sprays it is important not to sniff them up your nose because this will carry the medicine into the throat rather than having it stay in the nose where it gets absorbed faster.

Since we are on the topic of nasal sprays, I should mention three other nasal sprays that can be used to treat headaches. Migranal nasal spray contains dihydroergotamine, which is one of the strongest injectable migraine medications. However it is a lot less effective in a nasal spray form. Sprix is a nasal spray of ketorolac (Toradol), a nonsteroidal anti-inflammatory drug, which is also much stronger when injected. It is also available in a tablet, but the tablet is not any stronger than aspirin or ibuprofen. The third nasal spray is Stadol NS and it contains butorphanol, a strong narcotic pain killer. It should be avoided because it is very addictive.

A combination pill containing 10 mg of sumatriptan with 60 mg of naproxen sodium was just approved by the FDA for children aged 12 to 17. This combination in a higher dose (85 mg of sumatriptan and 500 mg of naproxen) has been available for adults for the past 7 years. This recent FDA approval allows children to take up to one adult strength tablet a day. It is good to have a smaller size tablet for kids. However, there is a big issue of cost. We don’t yet know what the pediatric strength tablet will cost, but a single tablet of the adult strength Treximet is $75. Yes, $75 for one tablet, even with a coupon you can get at GoodRx.com and $80 or more without a coupon. Very few insurance companies will pay for Treximet because you can get a generic tablet of sumatriptan (Imitrex), 100 mg for $1.50 and a tablet of naproxen, 500 mg for 7 cents. So, make-your-own Treximet will cost you $1.57. A very rare patient will tell me that they get better relief from the branded pill, which is possible because of the inactive ingredients, speed of onset and occasionally poor quality generics (I wrote about this problem in a previous post). However, such patients are very few.

Besides Treximet, we have two other triptans approved for migraines in children. Rizatriptan (Maxalt, Maxalt MLT) is approved by the FDA for children and adolescents 6 to 17 years of age and it is available in a generic form. Almotriptan (Axert) is approved in adolescents, 12 – 17 years of age, but it is available only as a branded drug ($40 a pill). In the UK, 10 mg sumatriptan nasal spray (Imitrex in the US, Imigran in the UK) was approved for adolescents, ages 12-17, who suffer from migraine and cluster headaches. In the US, we have only 5 and 20 mg nasal sprays of sumatriptan, and both are available in a generic form. Sumatriptan and zolmitriptan (Zomig, Zomig ZMT – orally disintegrating tablet, Zomig NS – nasal spray) were also tested in kids. The reason these two drugs were not approved is because the placebo response in kids tends to be very high and the active treatment was not distinguishable from placebo. This is mostly because headaches in children tend to be shorter in duration and the headache goes away on their own in a couple of hours, making it difficult to separate the active drug from placebo. However, they are probably as effective and as safe as the triptans approved in pediatric patients.

Doctors in St. Louis, MO examined how well headaches are treated in children. There has been little research about how well doctors in the US care for children and teens with migraine and if the treatment is consistent with evidence-based guidelines. They also assessed how often opioids (narcotics) are prescribed for children with migraines. The study used Electronic Health Record data to look at how almost 40,000 children and teens with migraine who presented to primary care providers, specialty care, or Emergency Room or Urgent Care (ER/UC) across four states in metropolitan and non-metropolitan areas were treated from 2009-2014.

The results showed that among children and teens presenting for care for migraine or likely migraine, nearly half (46%) were not prescribed or recommended any medication. Only one in six (16%) were prescribed or recommended an evidence-based medication. Among those who received medication, nearly one in six (16%) were prescribed an opiod (narcotic), and these numbers are even higher among teens 15-17.

The findings also revealed that the odds of getting an evidence-based medication were significantly higher if migraine was diagnosed, and the odds of getting any medication (evidence-based or not) were higher in non-metropolitan areas. Children and teens treated in a specialty care setting or the ER/UC were twice as likely to be prescribed an opioid than if treated in primary care.

The authors concluded that “Too many children who present for migraine or likely migraine are not getting any medication for their pain. Too few are receiving care consistent with evidence-based guidelines. And far too many are being prescribed an opiod. Five out of six children and teens are receiving suboptimal migraine care. A significant need exists to increase doctor awareness of the benefits of optimal migraine care and the potential dangers of prescribing opioids for children and teens with migraine.”

Guidelines issued by many medical organizations call for the use of ibuprofen as the first line treatment, however most children with severe migraines need to take a triptan. Triptans include sumatriptan (Imitrex), rizatriptan (Maxalt), zolmitriptan (Zomig), and four other similar drugs. Rizatriptan has been shown to be effective in children as young as 6, while other triptans have been approved for children older than 12. It is very likely that, just like in adults, some children respond better to one triptan and several triptans may need to be tried to find the best one. Just because the FDA approved one triptan for children above the age of 6 and another above the age of 12, it does not mean that there is a significant difference among the seven available triptans. These are safe drugs that have been in use for over 20 years and several of them are available in Europe without a prescription.

Placebo effect is a well-documented phenomenon, which is particularly pronounced when treating migraine headaches. Intravenous (IV) infusion of saline water is a placebo commonly used in studies where placebo is compared to a medication also given IV.

It is baffling why a group of Canadian physicians decided to test the effect of (IV) fluids on migraines in children and adolescents seen in an emergency room (the study was just published in Headache). They compared a group of children who were told that they will get only IV fluids with another group who was told that they might also get a medication with the IV fluids. The second group actually watched a nurse add something to the bag of IV fluid, but the children were not told that it was just more of the saline water. The researchers thought that the expectation of getting a medicine will help relieve their migraine headache. In fact neither group, the one who received IV fluids without expecting any medicine and the group who thought that they may be getting medicine had much relief. Strangely, the doctors concluded that additional studies using larger volumes of IV fluids are warranted. As if there is a chance that giving more fluids will stop a severe migraine. Sadly, intravenous fluids are often used in emergency rooms as a treatment for migraines in adults and children and we did not need this study to show that it is an ineffective approach. Doing more such studies seems unethical. Imagine a parent getting up in the middle of the night, taking a sick child to an emergency room where the child receives only intravenous fluids and is sent home with the child still in pain.

Emergency rooms, even in the medical mecca of New York City, are notorious for using ineffective treatments for migraine headaches. If not intravenous fluids, patients often get narcotic (opioid) pain killers, tranquilizers, or antihistamines, such as Benadryl. Some patients are just given a tablet of ibuprofen and are sent home after waiting for hours to be seen and treated. Here is a previous post on what to ask for if you end up in an emergency room with a severe migraine. Obviously, some doctors will not comply with your request, but it is worth asking.

Besides many other mental and physical problems, bullying in school causes headaches. This is the conclusion of a group of psychologists at the University of Padua in Italy who published their findings in the last issue of the journal Headache. They looked at 20 published studies on bullying, which included 173,775 children, and found that 14 of these studies recorded the presence of headaches. While 19% of kids who were not bullied suffered from headaches, this number was 33% in those who were. There was no difference in the incidence of headaches between kids in Europe compared to other countries.

This study confirms what has been reported for health problems in bullied kids in general. It is well known that psychological stress causes physical symptoms. Social pain is a term that psychologists use to describe the effect of peer rejection, ostracism, or loss. Recent studies have shown that physical and social pain share many physiological mechanisms in the brain. The authors also speculate that lack of coping skills, low self-esteem or lack of assertiveness may lead to more psychological and physical problems. They also call on pediatricians, school nurses and others to become more aware of the physical symptoms, such as headache, as a manifestation of bullying.

I have seen a number of children with severe persistent headaches, which required home schooling. In some of these kids bullying was a definite contributing factor, although many children are reluctant to admit this even to their parents.

Half of the kids seen by pediatric headache specialists suffer from chronic migraines. Dr. Hershey and his colleagues at the Cincinnati Children’s Hospital presented results of a study that compared cognitive behavioral treatment combined with amitriptyline (an antidepressant used to treat migraine and other pains) with amitriptyline alone in children aged 10 to 17 who suffered from chronic migraines. This was a first randomized clinical trial in childred with chronic migraines. Combined psychological & pharmacological treatment has been reported to be effective in adults and children with chronic pain other than migraine. Psychological intervention was cognitive behavioral therapy (including biofeedback); pharmacological intervention was amitriptyline (goal dose of 1 mg/kg/day). The control group was taught attention control with equal to psychological intervention in terms of contact frequency and face-to-face time, and involved education and support. They enrolled 135 children with mean age of 14 years; 15% minority; 79% female. Mean baseline headache frequency was 21 days and mean baseline disability score was 68 (severe disability grade). There were no differences between groups at baseline.

For the combined group, a greater than 50% headache frequency reduction was seen in 66% at post-treatment (20 weeks later), 86% at 12-month follow-up. And most impressively, 71% no longer had chronic migraines at the end of treatment and 88% were not chronic at 12-month follow-up. The disability score dropped to below 20 (mild to no disability) in 75% at post-treatment and 88% at 12-month follow-up. These results were significantly better than in the control group of children. The authors concluded that the combined psychological and medication treatment in youth with chronic migraine shows clinically significant reductions in headache frequency and migraine-related disability. At 12-month follow-up, almost 9 out of 10 children no longer had chronic migraines and were mild to no disability grade. They also felt that the results of this study should immediately impact practice of headache medicine in children. However, they could be wrong speculating that based on the published studies in adults, cognitive-behavioral therapy with amitriptyline may be better than other medications and Botox injections. In order to prove this, they need to do a study directly comparing Botox injections with cognitive-behavioral therapy and amitriptyline. One other factor that is not mentioned by the authors is that chronic migraines often subside on their own, which was shown in a study of 122 Taiwanese adolescents.

Photo credit: JulieMauskop.com

Infantile colic seems to be a precursor or an early manifestation of migraine headaches in children. A new European study published in the journal JAMA supports an earlier American study mentioned in one of my previous blogs. This European study involved 208 children who were diagnosed with migraine at emergency departments found that 73% of them had a history of colic in infancy, compared with 27% of a control group of children. History of being colicky was as common in children and teens who suffered from both migraine with and without aura.

This study suggests that many colicky babies whose colic does not respond to any treatment directed at their digestive system may be suffering from migraine headaches. Some of these children may develop cyclic vomiting as they get older and then go on to have typical migraine headaches.

The researchers at two Italian and one French hospital did a second study involving 120 children with tension-type headaches. Only 35% of these children had a history of infantile colic, confirming that it is not any headache, but specifically migraine that is associated with infantile colic. Migraines are very common in children. Before puberty, about 6% of boys and girls suffer from migraines. After puberty, boys remain at 6% and the incidence of migraines goes upt o 18% in girls.

One of the authors of the study suggested that migraine medications might be effective for colicky babies, although this would require a controlled study. Such studies in infants are difficult to perform because of the unknown potential side effects, which understandably will lead to parent anxiety. However, the colic is painful and we know that pain even in infancy leads to harmful changes in brain chemicals and brain structure. A colicky baby also causes high stress for the parents.

In my practice, I’ve encountered many children with episodic and chronic migraines whose parents report infantile colic that gradually transformed into a typical migraine. So, unfortunately, migraine can start even before a child can begin to speak.

Art credit: JulieMauskop.com