Ophthalmologic Manifestations of Pediatric Headache Medication
- Author: Marc E Lenaerts, MD, FAHS; Chief Editor: Hampton Roy Sr, MD more...
Medication Summary
Therapies for secondary headaches depend on the cause, such as antibiotics for sinusitis, and are not the subject of this article. Only treatment of primary headaches is reviewed. Migraine is reviewed first, then tension-type headache, then less common syndromes. When a treatment is prophylactic and when it is symptomatic is clarified because this is critical.
Drugs exist that can be considered individually but cannot be recommended on a routine basis because either (1) they have not been studied specifically or used regularly in the pediatric population, or (2) they are not available in the United States. These medications are migraine preventatives: flunarizine, a calcium channel blocker (5 mg PO qd); gabapentin (100-300 mg PO tid); riboflavin (400 mg PO qd); and metoprolol (50-100 mg PO qd slow-release form). This list is not comprehensive.
It must be emphasized that the placebo effect in children is very high, as high as 55% for prophylactic agents and 69% for abortive ones.
Simple measures, such as sleeping for a few hours in a dark and quiet room, must not be overlooked.[27] However, doing so regularly may significantly affect the social and academic life of the youngster.
Abortive therapies should be used selectively. If possible, they should be used no more than 4 days in a month, per month, according to Termine et al, but they should be used early on in the course of the attack. Overall, acetaminophen, 15 mg/kg, ibuprofen, 7.5-10 mg/kg, and sumatriptan, 5 and 20 mg nasal spray, should be considered.[28]
Prophylactic agents can and should be used for daily headache, and they can be considered for over 4 attacks per month for more than 2 months. This has to be addressed clearly with the parents, since it requires a level of commitment.
Beta-blockers
Class Summary
Effective in prophylactic therapy possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.
Propranolol (Inderal, Inderal LA)
Extensively used in migraine prevention in adults and children. Mechanism of action in migraine prevention is supposed to be a reduction of central noradrenergic activity. Tolerated best with a titration of the dose over 1-2 wk. The ideal dosage will reduce heart rate by about 20%.
Anticonvulsants
Class Summary
Those that interact with the GABA-ergic system seem to have a positive effect in reducing migraine attacks.
Valproic acid
Used for migraine prevention since the early 1990s and now has become one of the leading choices. Also used in epilepsy and for mood control in manic-depressive disorder. Has not been formally approved for use in migraine in persons < 16 y (10 y for epilepsy); however, safe use younger than that age has been reported.
Topiramate (Topamax)
Approved in adults in August 2004, it has been a major asset of migraine prophylaxis. It has still not been approved in children, but initial studies point to good efficacy and tolerability.
Tricyclic antidepressants
Class Summary
Prevention of tension-type headache. Used for migraine prophylaxis because it decreases the incidence and severity of attacks.
Amitriptyline (Elavil)
Tricyclic antidepressant used traditionally for migraine prophylaxis. Antimigraine effect is independent from antidepressant effects. Mechanism of action is not clear but possibly is due to enhanced central serotoninergic and noradrenergic. Cannot be formally recommended for individuals < 12 y. Amitriptyline also has been used for long-term prophylactic treatment of chronic tension-type headache. Mechanism of action is possibly central serotonin enhancement but has never been proven.
Calcium channel blockers
Class Summary
May relax smooth muscles and increase oxygen delivery during vasospasms.
Verapamil (Calan, Verelan, Covera-HS, Isoptin)
Efficacy in adults not as strong as other preventative agents mentioned above, but drug will be used in children for migraine with aura and basilar migraine. The drug has not been FDA approved for use in migraine. Another calcium channel blocker that is used extensively in countries other than the United States for migraine prevention is flunarizine; not scheduled to be approved in the United States.
Antihistamines
Class Summary
Compete for H1 receptor sites on effector cells in blood vessels and other target tissues.
Cyproheptadine (Periactin)
Useful in migraine prophylaxis. An antihistamine that has been used for migraine prevention in children more than in adults. Usually well tolerated. Mechanism of action not clarified and hypotheses include antihistaminic and anti-5-HT 2 effects.
Simple analgesics
Class Summary
Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients in pain.
Acetaminophen (Tylenol, Children's Tylenol, Feverall, Tempra)
For migraine symptomatic relief and symptomatic relief of tension-type headache. Efficacy in relieving tension-type headache modest. A specific analgesic fairly effective in migraine attack termination, especially when combined with antiemetic.
Combinations with pseudoephedrine (Sudafed) or caffeine (Excedrin Migraine) can be considered but should not be used regularly short of a risk of rebound withdrawal headache. Dosage forms include tab, cap, supp, and syrup.
Acetaminophen 15 mg/kg was slightly less effective than Ibuprofen 10 mg/kg at 2 hours, but equally at 1 hour, in a randomized controlled trial (RCT) by Hamalainen et al. There was no serious adverse events.
Antiemetics
Class Summary
Used as adjuncts or directly useful in symptomatic relief of migraine attacks. Interestingly, sometimes the gastrointestinal symptoms may be at the forefront of the clinical picture and require the most attention, as opposed to the pain. This can significantly differ from the management of adults with migraine. Delayed gastric peristalsis can hinder medication absorption.[29]
Promethazine (Phenergan)
Combines an antiemetic effect but also a direct antimigraine effect because of antidopamine action. Usually well tolerated. Exists in tablets, injection, and suppositories.
Triptans and dihydroergotamine (DHE) (ergot derivative)
Class Summary
Specific serotonin 1B and D agonists act on at least 2 sites in the trigeminovascular system (blockage of neuropeptide release, vasoconstriction, and probably blockage of central transmission at the second-order neuron level). They relieve not only pain but also nausea, vomiting, photophobia, and phonophobia. Change in taste seems to be the most common side effect.
Sumatriptan (Imitrex)
For migraine symptomatic relief. As of now, use of this class of drugs for migraine relief in pediatrics has not been formally approved. However, evidence has accumulated regarding efficacy and safety in this population by several clinical studies, and many pediatric neurologists are beginning to use them in children. The decision to choose these drugs might be best reserved for consultation.
Sumatriptan nasal spray in teenagers has been among the most extensively studied. Results of RCTs, however, are mitigated: statistically significant in Ahonen et al (nasal spray, 10 and 20 mg, ages 8-17; 51% relief rate vs 29 % for placebo) and Uberall et al; barely significant in Winner et al in 2006 (20 mg nasal; 2-hour response 68% vs 58% for placebo); and no significant advantage over placebo in Hamalainen et al in 1997 and Winner et al in 2000.
Sumatriptan, subcutaneous, in small doses for severe migraine can be considered, but it has not been specifically studied. Use in persons < 12 y not recommended. Sumatriptan is particularly convenient because of its 3 forms of administration, including the injectable form (in an injection pen) of 4 or 6 mg, and a prefilled syringe or a vial with 6 mg/0.5 mL, allowing delivery of an adjustable amount, as opposed to the STAT dose pen, in which the dose cannot be adjusted.
Profile of naratriptan is different from all other triptans, as it has a long half-life with a slow onset and prolonged duration of action. Differences between the other drugs (eg, oral sumatriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan, eletriptan) are modest. Zolmitriptan and rizatriptan are available in orally disintegrating tablets that are convenient for the pediatric patient.
Dihydroergotamine (Migranal)
Ergot derivatives include ergotamine and dihydroergotamine. Ergotamine only comes PO and has significant adverse effects, including vomiting, which makes it far less suitable than other drugs for the treatment of migraine. Dihydroergotamine is used parenterally for severe migraine attacks in the adult patient and can be considered in some instances in children. No head-on trial on DHE in children has been performed, but a 1997 investigation by Hamalainen et al of children with acetaminophen or ibuprofen failure trended toward positive but was not statistically significant.
Before administering, spray has to be primed by squirting 3 times. Once opened, the vial has an 8 h conservation duration, beyond which it must be discarded.
Steroids
Class Summary
May decrease intracranial pressure in benign intracranial hypertension.
Prednisone (Deltasone)
Not used as often anymore but should still be part of the armamentarium. Should be emphasized that treatment of this condition should be best left to the neurology/neurosurgery specialist. Should be part of an integrated treatment approach, including decompressive procedures.
Carbonic anhydrase inhibitors
Class Summary
Treatment of idiopathic intracranial hypertension.
Acetazolamide (Diamox)
Decreases the production of CSF and has diuretic effects. Has not been formally recommended for pediatric use and should be reserved for consultation.
Nonsteroidal Anti-inflammatory Drugs (NSAIDS), Oral
Ibuprofen
In migraine, the trigeminovascular activation implies local inflammation, which can be controlled by nonsteroid anti-inflammatory drugs (NSAIDs).
In a migraine RCT by Lewis et al, 7.5 mg/kg reduced severity of headache by 76%, vs 53% for placebo. In another RCT by Evers et al, it performed similarly to zolmitriptan.
Of note, other NSAIDs have not been studied in RCTs.
Antimigraine Agent
Rizatriptan
Similar to Sumatriptan.
An RCT by Winner et al proved no better than placebo in adolescents. Only an open-label, long-term investigation by Visser et al seems to indicate a small advantage over standard care (pain relief at 2 hours 77% for 5 mg ,vs 64 % for placebo).
Zolmitriptan
For migraine symptomatic relief. As of now, there has been no formal approval for the use of these drugs in migraine relief for children.
However, there is accumulating evidence of efficacy and safety in that population by several clinical studies, and many child neurologists are beginning to use them in children. The decision to choose these drugs might be reserved best for consultation. See Evers et al in Ibuprofen.
Serotonin Agonist
Eletriptan
For migraine symptomatic relief. As of now, use of this class of drugs for migraine relief in pediatrics has not been formally approved.
An RCT by Winner et al in 2007 did not indicate a benefit in the primary outcome over placebo (headache relief at 2 hours).
Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine.
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