Migraine secondary prevention

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

Secondary Prevention

Preventive Drugs

Following treatment of an acute migraine, it is important to consider preventive measures. Factors that prompt consideration of such measures include:

1) More than two migraines per month with disabilities lasting three or more days per month;

2) Failure of acute treatments;

3) Contraindications to acute treatments;

4) Adverse reactions from acute treatments;

5) Use of acute treatments more than twice a week;

6) Presence of uncommon symptoms such as hemiplegia, prolonged, aura, or migraine infarction.

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:

• Beta blockers such as propranolol and atenolol. A meta-analysis by the Cochrane Collaboration of nine randomized controlled trials or crossover studies, which together included 668 patients, found that propranolol had an "overall relative risk of response to treatment (here called the 'responder ratio')" was 1.94.
• Anticonvulsants such as valproic acid and topiramate. A meta-analysis by the Cochrane Collaboration of ten randomized controlled trials or crossover studies, which together included 1341 patients, found anticonvulsants had an "2.4 times more likely to experience a 50% or greater reduction in frequency with anticonvulsants than with placebo" and a number needed to treat of 3.8. However, concerns have been raised about the marketing of gabapentin.
• Antidepressants include tricyclic antidepressants (TCAs) such as amitriptyline and the newer selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. A meta-analysis by the Cochrane Collaboration found selective serotonin reuptake inhibitors are no more effective than placebo. Another meta-analysis found benefit from SSRIs among patients with migraine or tension headache; however, the effect of SSRIs on only migraines was not separately reported. A randomized controlled trial found that amitriptyline was better than placebo and similar to propranolol.

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.

Physical Therapy

Many physicians believe that exercise for 15-20 minutes per day is helpful for reducing the frequency of migraines.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

At least two British 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 good 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. Wilmut, E. B. (1956) "Migraine". Br. J. Physiol. Opt. 13, 93–97, replicated Turville's work. Both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. Neither study is available online, but another study that found that precision tinted lenses may be an effective migraine treatment and which references the Turville and Wilmut studies can be found at . Turville's and Wilmut's conclusions have largely been ignored since 1956 and it is widely believed that vision problems are not migraine triggers. Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.

Herbal and Nutritional Supplements

50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 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 people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing 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, Young and Silberstein found that 61.3% of patients treated with 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.The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. Clinical trials have been carried out (example), and appear to confirm that the effect is genuine (though it does not completely prevent attacks). 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. Kudzu Monograph at Med-Owl. 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. The supplement 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.Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center presented medical research on 47 candidates that demonstrated that 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 its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines. 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.

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. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001

Biofeedback has been used successfully by some to control migraine symptoms through training and practice. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001There 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. Mauskop A: "Alternative therapies in headache: Is there a role?" In: Medical Clinics of North America 85 (4): 1077-1084, 2001. 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.

New

Shown below is an image depicting the classification of migraine specific therapies according to the American Academy of Neurology and the American Headache Society.

Level A Established efficacy	Level B Probable efficacy	Level C Possible efficacy
Anti-epileptic Divalproex sodium 250 - 500mg twice a day Extended release - 500 - 1000mg per day Sodium valproate 250 - 500mg twice a day Topiramate 50mg twice a day Beta blockers Propanolol 80-240mg per day (divided in 3 to 4 doses) Timolol 10 - 15mg twice a day Metoprolol 47.5 - 200mg per day Triptans Fovatriptan 2.5mg per day	Antidepressants Amitriptyline 25 - 150mg per day Venlafaxine 150mg per day (extended release) Beta blockers Atenolol 100mg per day Nadolol 40 mg per day Triptans Naratriptan 2.5mg per day Zolmitriptan 2.5mg per day	ACE inhibitors Lisinopril Angiotensin receptor blocker Candesartan Alpha agonists Clonidine Guanfacine Anti-epileptic Carbamazepine Beta Blockers Nebivolol Pindolol Antihistamines Cyproheptadine

	Side Effects
Anti-epileptic	Divalproex sodium Hepatotoxicity Sedation Nausea Weight gain Teratogenicity Sodium valproate Hepatotoxicity Sedation Nausea Weight gain Teratogenicity Topiramate Paresthesia Fatigue Nausea
Beta blockers	Propanolol Fatigue Exercise intolerance Timolol Fatigue Exercise intolerance Metoprolol Fatigue Exercise intolerance Atenolol Blurred vision Confusion Dizziness Orthostatic hypotension Sweating Weakness
Antidepressants	Amitriptyline Weight gain Xerostomia Sedation Venlafaxine Blurred vision Hypertension

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.

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 Fenoprofen 200 - 600mg Ibuprofen 200mg twice a day Ketoprofen 300mg three times a day Naproxen 500 - 1100mg Naproxen sodium 550mg twice a day Histamines Histamine SQ 1 - 10ng twice a week Vitamins and Minerals Riboflavin 400mg per day Magnesium 600mg per day
NSAIDs Flurbiprofen Mefenamic acid Herbal therapies, vitamins, and minerals Co-Q10 Estrogen Antihistamines Cyproheptadine

• The efficiency of NSAIDs and other complementary therapies are limited, other pharmacological therapies should be received before.
• Frecuent medication use or high doses, could increase the risk of headache progression ot medication overuse, leading to secondary health complications such as:
  • Gastrointestinal bleeding - with NSAIDs or Aspirin
  • Headache rebound - with discontinuation of feverfew.

Not Recommended according to the American Academy of Neurology and the American Headache Society

Level A	Level B	Level C
Lamotrigine	Clomipromine Montelukast	Acebutol Clonazepam Nobumetone Oxacarbazepine Telmisartan

Recommended for short-term prevention of Menstruation associated Migraine

	Drugs	Doses
Level A	Fovatriptan	2.5mg bid perimenstrually
Level B	Naratriptan Zolmitriptan	1mg bid for 5 days perimenstrually 2.5mg bid or tidperimenstrually
Level C	Estrogen	1.5mg estradiol in gel for 7 days perimenstrually

Management for Prophylaxis

Patient appointed for Migraine Prophylaxis

Consider first-line agent ❑Divalproex ❑Sodium Valproate ❑Propanolol ❑Topiramate

Adverse effects?

If not effective after two or three months, adjust dose successively until effective

If first-line agent not effective at maximum dose, or adverse effecty; try different first-line agent

If no single first-line agent is effective or tolerable; consider a combination of two first-line agents

If no f no single first-line agent or combination of two first-line agents is effective or tolerable; consider an alternative agent

❑Atenolol or Metoprolol ❑Feverfew ❑Naproxen ❑Naproxen sodium ❑Magnesium ❑Riboflavin