Migraine secondary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Following treatment of an acute migraine, it is important to consider preventive measures. Pharmacotherapy for secondary prevention includes NSAIDs, amitryptyline, divalproex sodium, valproic acid, propranolol, timolol and topiramate among others. If the preventive measure is not effective after two to three months, the dose of the medication should be adjusted. If no improvement is noted, another first line therapy or a combination of two first line therapies should be initiated.[1]

Indications for Pharmacologic Prophylaxis of Migraine

According to the guideline from American Academy of Neurology (AAN), prophylaxis may be more appropriately guided by one or more of the following:[2]

  • Recurring migraines that, in the patients' opinion, significantly interfere with their daily routines, despite acute treatment
  • Frequent headaches
  • Contraindication to, failure of, or overuse of acute therapies
  • Adverse events with acute therapies
  • The cost of both acute and preventive therapies
  • Patient preference
  • The presence of uncommon migraine conditions, including hemiplegic migraine, basilar migraine, migraine with prolonged aura, or migrainous infarction.

European Federation of Neurological Societies (EFNS) proposed that prophylactic treatment should be considered and discussed with the patient when:[3]

  • The quality of life, business duties, or school attendance are severely impaired
  • Frequency of attacks per month is two or higher
  • Migraine attacks do not respond to acute drug treatment
  • Frequent, very long, or uncomfortable auras occur

United States guidelines recommend to initiate preventive therapy when attacks regularly exceed two times per week, whereas European guidelines suggest migraine prophylaxis for two or more attacks per month.[3][4]

Pharmacological Prevention

The main goal of preventive therapy is to reduce the frequency, severity, and durations of migraines, and to increase the effectiveness of abortive therapy. Another reason is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is an extremely common problem among migraneurs. This occurs in part due to overuse of pain medications. MOH results in the development of chronic daily headache due to "transformed" migraine. Preventive medication has to be taken on a daily basis, usually for a few weeks, before the effectiveness can be determined. Supervision by a neurologist is advisable. A large number of medications with varying modes of action can be used. Selection of a suitable medication for any particular patient is a matter of trial and error, since the effectiveness of individual medications varies widely from one patient to the next. Often preventive medications do not have to be taken indefinitely. Sometimes as little as six months of preventive therapy is enough to "break the headache cycle" and then they can be discontinued. The most effective prescription medications include several drug classes:

Other drugs:

  • Sansert was withdrawn from the US market by Novartis, but is available in Canadian pharmacies. Although highly effective, it has rare but serious side effects, including retroperitoneal fibrosis.
  • Namenda, memantine HCI tablets, which is used in the treatment of Alzheimer's Disease, is beginning to be used off label for the treatment of migraines. It has not yet been approved by the FDA for the treatment of migraines.
  • ASA or Asprin can be taken daily in low doses such as 80 to 81 mg, the blood thinners in ASA has been shown to help some migrainures, especially those who have an aura.


Migraine Specific Therapies

Classification, Dosage, and Side-Effects of Migraine Preventive Therapies.[11][12]
Evidence Agent Dosage Potential Side-Effects
Level A
Medications with
established efficacy
(>2 Class I trials)
Antiepileptic Drugs
Divalproex sodium 250 mg twice daily Drowsiness, weight gain, tremor, hair loss, fetal abnormalities, hematological or liver abnormalities
Sodium valproate 400–600 mg twice daily Drowsiness, weight gain, tremor, hair loss, fetal abnormalities, hematological or liver abnormalities
Topiramate 50–200 mg daily Paresthesia, cognitive dysfunction, weight loss, care with a family history of glaucoma, nephrolithiasis
Beta Blockers
Metoprolol 25–100 mg twice daily Reduced energy, tiredness, postural symptoms; contraindicated in asthma
Propranolol 40–120 mg twice daily Paresthesias, sleepiness, gastrointestinal intolerance
Timolol 10 mg twice daily Reduced energy, tiredness, postural symptoms; contraindicated in asthma
Triptans (short-term prophylaxis of menstrually-related migraine)
Frovatriptan 2.5 mg twice daily Coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, arrhythmia
Level B
Medications are
probably effective
(1 Class I or
2 Class II studies)
Antidepressants/SSRI/SSNRI/TCA
Amitriptyline 25–75 mg every night Nausea, vomiting, drowsiness, hypersomnolence, dry mouth, concentration difficulties
Venlafaxine 75–150 mg daily Nausea, vomiting, drowsiness
Beta Blockers
Atenolol 50 mg daily Reduced energy, tiredness, postural symptoms; contraindicated in asthma
Nadolol 80–240 mg daily Reduced energy, tiredness, postural symptoms; contraindicated in asthma
Triptans (short-term prophylaxis of menstrually-related migraine)
Naratriptan 1 mg twice daily Dizziness, chest pain, malaise
Zolmitriptan 2.5 mg twice daily Asthenia, headache, dizziness, nausea
Level C
Medications are
possibly effective
(1 Class II study)
ACE Inhibitors
Lisinopril 20 mg daily Cough, dizziness
Angiotensin Receptor Blockers
Candesartan 16 mg daily Birth defects and fetal death
Alpha Agonists
Guanfacine 1 mg daily Dizziness, drowsiness, headache, constipation, diarrhea, loss of appetite, fatigue, nasal congestion
Antiepileptic Drugs
Carbamazepine 200 mg daily Drowsiness, motor coordination impairment, upset stomach
Beta Blockers
Nebivolol 5 mg daily Fatigue, clinical depression, bradycardia, impotence
Antihistamines
Cyproheptadine 4 mg twice daily Weight gain, abdominal discomfort, diarrhea, nausea, vomiting, xerostomia, depression, somnolence
Calcium Channel Blockers
Nicardipine 20 mg twice daily Headache, upset stomach, dizziness, fatigue, numbness, palpitations, constipation, heartburn


NSAIDs and Complementary Drugs

Shown below is an image depicting the classification of NSAIDs and complementary drugs for migraine prevention according to the American Academy of Neurology and the American Headache Society.[1]

Level A
Established efficacy
Level B
Probable efficacy
Level C
Possible efficacy
Petasites
  • 50 - 300mg BID
  • 2.08 - 18.75 TID for MIG-99 preparation
NSAIDs



Histamines



Vitamins and Minerals

NSAIDs



Herbal therapies, vitamins, and minerals



Antihistamines

  • Cyproheptadine


Non Pharmacological Prevention

Physical Therapy

Many physicians believe that exercise for 15-20 minutes per day is helpful for reducing the frequency of migraines.[13] Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines. However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments.Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that myofascial release can relieve this tension and in doing so reduce or eliminate the stress headache element.

Prism Eyeglasses

Two studies have shown a relationship between the use of eyeglasses containing prisms and a reduction in migraine headaches. Turville, A. E. (1934) "Refraction and migraine". Br. J. Physiol. Opt. 8, 62–89, contains a review of the literature and theories existing in 1934, and includes the vascular theory of migraine, which is popular today. In that study, Turville suggests that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.

Herbal and Nutritional Supplements

It was shown in a controlled trial that 50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was asoociated 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex®, does not.

Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. It has been reported to help relieve the nausea and dull the head pain, as well as to possibly prevent the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis increases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine.

Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial,[14] Young and Silberstein found that 61.3% of patients treated at a dose of 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results.[15]

The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. Clinical trials have been carried out, and appear to confirm that the effect is genuine (though it does not completely prevent attacks).[16]

Kudzu root (Pueraria lobata) has been demonstrated to help with menstrual migraine headaches and cluster headaches. While the studies on menstrual migraine assumed that kudzu acted by imitating estrogen, it has since been shown that kudzu has significant effects on the serotonin receptors.

Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9-12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group.[17]

Supplemental riboflavin or Vitamin B2 has also been used, often with magnesium citrate, to reduce the number of migraines. Its effectiveness is less well documented.

Non-Drug Medical Treatments

Botox is being used by many headache specialists for patients with frequent or chronic migraines with encouraging results.[18] Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.[19] Transcranial Magnetic Stimulation (TMS), a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among patients.[20] This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines.[21] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light. Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.[22]

Alternatives

Because the conventional approaches to migraine prevention are not 100% effective and can have unpleasant side effects, many seek alternative treatments. Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing. Sometimes acupuncture is used to relieve the pain of an active migraine headache. In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture. Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents.

Biofeedback has been used successfully by some to control migraine symptoms through training and practice. There is evidence that magnesium supplements can reduce the frequency of migraine headaches. Riboflavin (vitamin B2), co-enzyme Q10 and butterbur extract has been also subjected to double-blind studies suggesting their efficacy in preventing migraine headaches.

Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided. Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches. Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs.

A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements.

Massage therapy of the jaw area can also reduce such pain. Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases. In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache.

References

  1. 1.0 1.1 Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; et al. (2012). "Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 78 (17): 1337–45. doi:10.1212/WNL.0b013e3182535d20. PMC 3335452. PMID 22529202.
  2. "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management for Prevention of Migraine" (PDF).
  3. 3.0 3.1 Evers, S.; Afra, J.; Frese, A.; Goadsby, PJ.; Linde, M.; May, A.; Sándor, PS. (2006). "EFNS guideline on the drug treatment of migraine - report of an EFNS task force". Eur J Neurol. 13 (6): 560–72. doi:10.1111/j.1468-1331.2006.01411.x. PMID 16796580. Unknown parameter |month= ignored (help)
  4. "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management for Prevention of Migraine" (PDF).
  5. Linde K, Rossnagel K. "Propranolol for migraine prophylaxis". Cochrane Database Syst Rev: CD003225. PMID 15106196.
  6. Chronicle E, Mulleners W. "Anticonvulsant drugs for migraine prophylaxis". Cochrane Database Syst Rev: CD003226. PMID 15266476.
  7. Steinman M, Bero L, Chren M, Landefeld C (2006). "Narrative review: the promotion of gabapentin: an analysis of internal industry documents". Ann Intern Med. 145 (4): 284–93. PMID 16908919.
  8. Moja P, Cusi C, Sterzi R, Canepari C. "Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches". Cochrane Database Syst Rev: CD002919. PMID 16034880.
  9. Tomkins G, Jackson J, O'Malley P, Balden E, Santoro J (2001). "Treatment of chronic headache with antidepressants: a meta-analysis". Am J Med. 111 (1): 54–63. PMID 11448661.
  10. Ziegler D, Hurwitz A, Hassanein R, Kodanaz H, Preskorn S, Mason J (1987). "Migraine prophylaxis. A comparison of propranolol and amitriptyline". Arch Neurol. 44 (5): 486–9. PMID 3579659.
  11. Silberstein, SD.; Holland, S.; Freitag, F.; Dodick, DW.; Argoff, C.; Ashman, E. (2012). "Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 78 (17): 1337–45. doi:10.1212/WNL.0b013e3182535d20. PMID 22529202. Unknown parameter |month= ignored (help)
  12. Goadsby, PJ.; Sprenger, T. (2010). "Current practice and future directions in the prevention and acute management of migraine". Lancet Neurol. 9 (3): 285–98. doi:10.1016/S1474-4422(10)70005-3. PMID 20170842. Unknown parameter |month= ignored (help)
  13. http://www.headachedrugs.com/pdf/HA2005.pdf] (PDF)
  14. Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia. 22 (2): 137–41. PMID 11972582.
  15. Sándor PS; et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology. 64: 713–715.
  16. Diener, HC.; Pfaffenrath, V.; Schnitker, J.; Friede, M.; Henneicke-von Zepelin, HH. (2005). "Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention--a randomized, double-blind, multicentre, placebo-controlled study". Cephalalgia. 25 (11): 1031–41. doi:10.1111/j.1468-2982.2005.00950.x. PMID 16232154. Unknown parameter |month= ignored (help)
  17. Peikert A, Wilimzig C, Köhne-Volland R (1996). "Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study". Cephalalgia. 16 (4): 257–63. PMID 8792038.
  18. Samton JB and Mauskop A. The treatment of headaches with Botulinum Toxin. Expert Review of Neurotherapeutics March 2006, Vol. 6, No. 3, Pages 313-322.
  19. Matharu MS, Bartsch T, Ward N, Frackowiak RS, Weiner R, Goadsby PJ (2004). "Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study". Brain. 127 (Pt 1): 220–30. PMID 14607792.
  20. "The Ohio State University Wexner Medical Center". Retrieved 2012-08-30.
  21. "Technology | The Times". Retrieved 2012-08-30.
  22. Mohammad, Yousef (2006-06-22). "Magnets Zap Migraines". 49th Annual Scientific Meeting of the American Headache Society. Los Angeles, California. Retrieved 2006-07-04. Check date values in: |date= (help)