More about NDPH

Let’s talk today about the story of NDPH, a primary headache not well understood or recognized, a zebra among headaches. The more we know about it, the more it is recognized.  But that does not make it any easier to deal with as a provider or a patient.

The first documented description of NDPH was in 1986, by Dr. Walter Vanast, a neurologist in Canada. He described it as a benign syndrome that resolved regardless of treatment in 73-86% in 3-24 months. In a recent interview with Dr. Vanast in Headache journal, he describes his interest and search for the cause of this headache. He thought it was an auto‐immune disorder with a persistent viral trigger, such as EBV. And this description is still in use today, though in my opinion ‘benign’ is not the word I would use.

About half of patients with NDPH have had a febrile viral illness near the onset. Others develop it after a minor head injury, or pseudotumor or idiopathic intracranial hypertension (IIH). Others seem to have no known reason for this headache to develop. There continues to be very little known about the pathophysiology of NDPH.  A recent paper stated that it might be related to persistent central nervous system inflammation or related to cervical hypermobility. We really don’t know.

The incidence in adult of chronic daily headache is 4%; the incidence of these adult patients having NDPH is between 1-10%, so not that many. But in children and teens, the incidence is much higher: 20-40% of pediatric chronic daily headache patients. Way more kids and teens than adults have NDPH. And it is probably underreported and under recognized.

There are several different patterns of headache associated with NDPH.

  • The first type is mild and self-limiting, resolving without therapy.
  • The second type is moderate, with a constant headache that waxes and wanes over time. Good days are more like tension-type headaches and bad days are more like migraine.
  • The third type is a continuous severe headache, with disabling high-level pain all day every day.

We don’t see many patients with the first type, with lower level headaches that just end up going away. Most commonly we see the second type, kids with constant all day every day headache, pain rated 5-6/10NRS on average with a range of 3-9/10NRS. On lower pain days, they might have mild nausea, mild dizziness, mild mental fogginess and light sensitivity along with headache. On higher pain days, all of their symptoms are severe and migrainous; pain is 8-9/10NRS, and they are non-functional. Their pain and symptoms are disabling; change in pain level is influenced by activity, weather patterns, stress and cognitive effort.  Fortunately, while we do see the completely refractory third type, they are not as common– but so difficult.

So it is hard enough to have a constant headache, no headache-free time. But add to that is the realization that most common treatments and even the most aggressive treatments are ineffective against this headache. Current daily medications do not alleviate their pain and the patients just experience all the side effects.

Usually by the time the patient arrives at our specialty headache program, they have already tried at least 1 or more daily medications without success. The families might like to try more medication, so we would pick another of the common ones. The choice is often based on what other symptoms are most bothersome.

  • Unable to sleep? Choose amitriptyline or gabapentin.
  • Worried about weight gain? Choose topiramate.
  • Don’t want any mental clouding? Try propranolol.
  • Super dizzy? Try verapamil.
  • Persistent nausea? Add hydroxyzine at bedtime.
  • Very tight neck and upper back muscle? Choose tizanidine.
  • Don’t want medications? Try a supplement- magnesium or riboflavin.
  • All else fails? Try occipital nerve and trigger point injections.

You might find that something helps other symptoms, even when it does nothing to the headache. I have had great results with using hydroxyzine at bedtime for patients with persistent nausea. Having less nausea may make the difference between going to school or staying home…. again.

It is just a matter of time before the families (really the patients) decide that they do not want to try any further medication, at least daily medication. Most tell me that they feel better off the meds.

Things you might try for a migraineur in status migrainosis such as going to the ED or being admitted for DHE are not usually helpful. Often the patients end up more frustrated, faced with another ineffective intervention.

As far as rescue medications, again you try the basics- NSAIDS, antiemetics, caffeine. Most important is to stress that analgesia should only be used for severe headache and no more than 3 days/week to avoid overuse headache. As you can imagine, overuse is tempting, kids just want to feel better.  But I stress that too much analgesia will just make them feel worse, and in the end, the medications will stop working. I encourage being strategic with analgesia. Save it for when you might really need it, such as before SAT exams or before a big sports game or concert.  This is generally effective in preventing overuse.

What is really important is for the families and patients to know that you are all in this together. Accepting where they are and working with them. Offering hope but being realistic.

I will have more to say about some research initiatives and novel approaches to NDPH in the next post.

Migraine medications to the rescue…..adjunct and combination therapies

There are 3 groups of medications that are used to treat a migraine attack: migraine abortives, analgesia, and adjuncts.  We have covered the migraine abortives (those medications specifically designed to stop the migraine attack) and analgesia (used to reduce pain) in the past 2 posts.   There are several medications that are used either in combination with others to treat the migraine or to treat other symptoms that happen with migraine.  These medications are referred to as adjuncts in migraine therapy, and are often used in combination.  Again, developing an individualized rescue plan is the key to living with migraine, rather than suffering from migraine.  Patients often need several medications for an effective rescue plan.

Adjuncts

Adjunct medications are those that are given with analgesia to complement and enhance the effect and treat other symptoms, such as nausea, dizziness or insomnia.  A classic combination is an NSAID with ondansetron (Zofran), or metoclopramide (Reglan) =/- benadryl, or prochlorperazine (Compazine). I will often encourage taking an adjunct with analgesia at the same time, and if appropriate, with their triptan.

The most common adjuncts are antiemetics, those medications which treat nausea associated with migraine. Antihistamines, such as diphenhydramine (Benadryl), meclizine, and/or hydroxyzine (Atarax) are useful in combination with NSAIDs.  There is the added benefit of drowsiness, to help facilitate restorative sleep.  Ondansetron is also useful for nausea, generally does not cause drowsiness.  Compazine and Reglan are seen as primary agents for treating migraine as well as treating nausea.  The side effects associated with these 2 medications can be avoided by using them with Benadryl.  Dosing is based on weight and age appropriate.

Another option often used in the ED is steroids, such as dexamethasone.  If a patient has had this in the ED, they could use this as an outpatient rescue as well.  Oral magnesium is sometimes used as a rescue medication too.

Treatment Combinations

Many patients develop a migraine rescue strategy, over time and with experience, that involves a combination of medications.  It is always a very individual plan and usually discovered by trial and error.  They might have reasonably good results with a triptan plus antiemetic, or triptan plus analgesia. They may have the best results with an ‘attack pack’ of 3 medications taken together, such as sumatriptan, naproxen and Benadryl.  In cases when a triptan is not effective, NSAID plus antiemetic is a good combination.

The key is to work with the family, figure out what works best, and then BE PREPARED for the migraine to happen.  For younger kids, their parents should always travel with a dose of each of their rescue medications.  They need to have several doses of each medication with the school nurse as well. Older teens can have a prepacked plastic bag with 1 dose of each medication that they can carry with them outside of school.  (Make sure it’s labelled, for obvious reasons).  Most high schools do not allow for self-medication. It is well worth it for the family to have a good relationship and understanding with the school nurse; that when the teen comes to the nurse’s office, they can get their medication promptly and have a chance to lie down and nap for up to 30 minutes at least. Having a clear plan communicated to the school nurse is so helpful.  The workload of our school nurses is tremendous, and having a collaborative relationship with them will make rescue therapy much easier and effective for the kids.

Complementary rescue remedies

In addition to the medications we have talked about, there are a number of complementary interventions that can really help resolve a migraine.

  • Aromatherapy: using an essential oil, such as peppermint, lavender, ginger, or a specially formulated blend (M’Grain from Young Living products) topically, gently massaged on the temples or behind the ears
  • Ice/cold (or heat) applied to the forehead or the neck
  • Gentle massage to the neck and occiput or frontal/temples
  • Anything that activates the relaxation response, such as a CBT or biofeedback exercise, breathing technique, using a relaxation/meditation app, soothing music.  My favorite is the Insight Timer app, so many options and free.

Final rescue thoughts

Having migraine is challenging for the whole family. Migraines often occur at the most inconvenient times, often out of the blue.  It’s important to remember that stress is a trigger for most patients, and stress is not always negative. Positive stress, such as excitement about an upcoming vacation trip, can also trigger migraine.

I also cannot emphasize enough how important it is to treat the migraine promptly- hit it hard and fast- for best results and resolution.  Giving parts of a rescue plan, half-doses spread out over time, usually just prolongs the episode and makes it more difficult to resolve. And there really is no point in prolonging the agony, especially when it is your kid’s pain.

Being prepared, having rescue medications, and extra electrolyte-rich hydration fluids can go a long way in turning a migraine episode from a disaster into a blip on the radar.

Migraine analgesic medications to the rescue……

There are 3 groups of medications that are used to treat a migraine attack: migraine abortives, analgesia, and adjuncts. . We covered the migraine abortives (those medications specifically designed to stop the migraine attack) in the last post. So let’s talk about analgesia now.  Analgesics are medications that are used to reduce the pain. Again, developing an individualized rescue plan is the key to living with migraine, rather than suffering from migraine.  Patients often need several medications for rescue.

Non-steroidal anti-inflammatory drugs (NSAIDS) are the mainstay of migraine analgesia. These include ibuprofen, naproxen, ketorolac, diclofenac, and others. The side effects are GI, such as gastric distress, nausea, ulcer, hematologic, such as bleeding disorder or platelet dysfunction, or related to allergic reaction.  Any of the NSAIDS can be effective in treating a migraine, as long as it is taken early in the episode.  Treating as soon as possible is the key to success.

Most people will start out with ibuprofen, which can be very effective. Dosing should be based on weight and age; under age 12 years and 40kg = 10mg/kg, to a max of 40mg/kg/day, and from 12-17 years and over 40kg = 400mg q6h, to a max of 1200mg/day. Higher dosing can be used in older teens but not more than 2400mg/day, not around the clock and/or daily.  Interestingly, there is a product called Motrin migraine or Advil migraine which contains solubilized ibuprofen 200mg. It is touted as having a quicker release of medication.  I would think that ibuprofen suspension or chewable tabs would work just as well, and in generic form would be cheaper.

Naproxen is used very often and is effective. It does come in a variety of forms, both prescription and over the counter (OTC), all doses q12h.  OTC is Aleve, which is 220mg/tab and is a useful formulation for those under 50kg. Over 50kg we usually use prescription strength naproxen 500mg, regular tabs. It also comes in extended release or enteric coated, but for quick action, the regular tabs work best. Naproxen also comes in smaller dosing (250mg, 375mg), and also as a suspension, 125mg/5ml, which is quite bad tasting.  Using a regular tab, crushing it in grape jelly, maple syrup or chocolate syrup, would be preferable to liquid naproxen.

There are several other prescription NSAIDS, such as Diclofenac and Sulindac, which can be tried also, if these others are ineffective. There are a number of other NSAIDS, but they are not used for rapid action or migraine rescue, such as celecoxib.

Ketorolac is the strongest of the NSAIDS, and comparable to morphine, without the risks of using an opioid. Caution should be used for patients with impaired renal function. Dosing is weight based. If your patient goes to the ED, most likely they will receive ketorolac (toradol) IV or IM, as a part of the treatment cocktail. Unfortunately, oral ketorolac is not particularly effective.  We have had patients use IM toradol at home for acute migraine treatment, which does involve teaching and comfort using a syringe and giving the injection.  We have families who will do it but not often.  We also will give an IM injection in the office if needed.

But there is good news in the world of ketorolac! Nasal ketorolac or Sprix is available now. You used to be able to get it through retail pharmacies. It then went off the market for a while and now it’s back.  It is only available through Cardinal health, a mail order pharmacy.  While it is a bit of a process to prescribe and administer, I have patients who just love it. It can be a game changer, keeping kids out of the ED.  To ePrescribe, you have to choose Cardinal health mail order (distributed by Egalet inc), make sure you document the patient’s weight, best phone number, and that it’s OK for patients under 18 years (they will call you if you don’t).  They will reach out to families for insurance information. Delivery by mail is quick.  It does need to be refrigerated, so another NSAID option should be available, if needed.  The nasal administration is a little tricky; you don’t want to use it like a regular nose spray, inhaling it up into your sinuses- it will burn like crazy.  Instead, you squirt it into the nare, squeeze your nose tight, and then breathe through your mouth while the med is absorbed through the mucous membranes in the nose or it runs down the throat.  I do a ‘demonstration’, and use the term ‘pant like a dog’ to describe how to do it.  The kids are unlikely to forget how to do it, after they watch me pant like a dog. I put more information in Resources.

Other options:

For patients who cannot take NSAIDS, there is always acetaminophen, dosed weight- appropriately. It can be reasonably effective, especially in combination.   Aspirin is included here as well, but should be used in a limited fashion due to the risk of Reye’s syndrome.  While most families do not use aspirin as go-to analgesic, they will often use Excedrin migraine (or in generic form), which is a combination of aspirin 250mg, acetaminophen 250mg and caffeine 65mg.  This is Ok to use in mid-older teens, but not if any viral illness is suspected.  Also not around bedtime, as there is considerable caffeine in this.

For patients who cannot take NSAIDS and for whom acetaminophen is not effective, a weak opioid, such as tramadol, can be used. We rarely prescribe it and reserve using it for patients with GI disorders (ex: Crohn’s) or NSAIDS allergy.  Some patients may receive an opioid such as dilaudid in the ED, but we never use this level of opioid- they are not effective, are not necessary and risky.

Another old-school medication often given in the ED or in the community is Fioricet, whch is a combination of acetaminophen, aspirin and butalbitol (a barbiturate). It is ineffective, sedating and addictive and not recommended for kids and teens. I have attached an article here about it.  Caruso et al 2015 (Butalbital and pediatric headache- Stay off

So that’s the latest on headache analgesia. In the next post, I will cover adjuncts and combinations of medications that work well to treat a migraine to wrap up rescue options.