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Overview of Migraine Acute Migraine Treatments
characteristics of migraine Office Migraine Rescue Treatments
Optimum Migraine Care Migraine Prevention Overview
Common Migraine Treatment Mistakes Oral Migraine Preventives
What doctors treat migraines? Procedures to Prevent Migraines
Migraines and Pregnancy Monocolonal Antibodies
Childhood and Pediatric Migraines Devices for Migraine Treatment and Prevention

Preventing a Migraine Headache (Oral Preventative Medications)

Are you trying to chose an oral agent to prevent your migraines. Fortunately there are many choices and they are all inexpensive. In general, the selections process initially begins with one of the highly effective migraine preventatives and then moves to less proven or less robust agents when the better agents are either not successful, not tolerated, or have side effects that makes patients want to avoid them completely. Dr. Loftus calls this method “intelligent trial and error.” Dr. Loftus considers 7 agents potential oral agents for first line therapy for frequent migraine prevention and chronic migraine prevention. The are amitriptylene, duloxeitne, propranolol, candesartan, topiramate, zonisamide, and valproic acid.

Elavil® (amitriptylene)

The primary advantage of Amitriptylene or Elavil® is that it is the cheapest preventative available. The monthly cost can literally be $5 per month. Unfortunately, the medication has a high percentage of side effects. Dry mouth, sedation, constipation, and weight gain are typically limiting side effects. Given the low cost of medications that have fewer side effects, Dr. Loftus rarely uses this medication.

Inderal® (propranolol or propranolol ER)

The next oldest, well established preventative is propranolol or Inderal®. This medication can worsen asthma, makes patients fatigue, and limit aerobic exercise but in general is fairly well tolerated. It is relatively inexpensive as well with a twice-daily generic form running about $15 per month. It is generally thought of as a weight neutral medication but all patients should be monitored for weight. It is one of the most common medications used for women who need prevention and need oral prevention at time of conception. If continued into the 2nd trimester, it can be associated with lower birth weight babies.

Topamax® (topiramate) and Zonegran® (zonisamide)

A third preventative is topiramate or Topamax®. This medication, first licensed as an antiepileptic medication, is the most popular medication currently prescribed by neurologists for headache prevention. While not more effective than the other first line agents, it is the only FDA approved migraine preventative that is clearly associated with weight loss. The average obese patient can expect to lose about 10% of their body weight over one year. Since obesity is a risk factor for frequent migraines over time, a large number of migraine patients who need preventatives are medically overweight or obese. Unfortunately topiramate does have a lot of side effects. Some side effects are more of a nuisance. Carbonated drinks taste badly while taking this drug and some patients experience tingling around the mouth, finger, or toes. Renal or kidney stones occur about 1-2% of the time and is the only side effect which does not go away when topiramate is discontinued without additional therapy. A small percentage of patients have an altered ability to think on the medication that commonly expressed as a word finding problem. This returns to normal with reduction or discontinuation of the medication. Finally there is a very rare condition of acute narrow angle glaucoma that is very painful but again resolves with discontinuation of the medication and specific medical therapy. The cost of generic topiramate is as low as $10 per month. More recently, branded extended release topiramate have been marketed under the names Qudexy® ($400-500 per month) and Trokendi® ($700-1000 per month). These medications have different methods to slow absoprion. Slower absorpion allows for lower peak doses of topiramate and higher trough doses. These medications therefore imply better migraine control with fewer side effects. They have very similar pharmacokinetics (the highs and lows) but the Qudexy has a few advantages over the Trokendi. Qudexy is cheaper at all of the commonly used doses and is much cheaper at 150 mg per day dose where Qudexy has a tablet of this size and Trokendi does not. Dr. Loftus will switch patient from generic to these more expensive trade name medications if a patient gets a side effect to generic topiramate but finds the medication useful.

Zonegran® or zonisamide is another antiepileptic medication with weight loss similar to topiramate. It has fewer mental side effects. In the only head to head study done between the two, they were equally effective for migraine prevention. Zonegran or zonisamide is generally avoided in sulfa allergic patients and tends to have a higher incidence of nausea than topiramate. The cost is typically $20-$40 per month. The half life of zonisamide is much longer than topiramate (63 hours vs 21 hours) and therefore it can be used once per day. According to the Epilepsy Registries available in 2020, it is also safe for pregnancy. Since zonisamide can be tolerated at a higher equivalent dose compared to topiramate so in practice it works better with more weight loss than topiramate.

Depakote ER® or valproic acid

The last of the big four preventatives is valproic acid and is typically $20-30 per month. The most convenient form for patients is Depakote ER® which is a once daily migraine prevention agent. Depakote ER® can cause birth defects and therefore, Dr. Loftus generally will not prescribe it to women who could become pregnant. In addition, valproic acid can cause weight gain and liver enzyme problems. Despite these warnings, the medication is generally well tolerated and can be used quite safely. However, given the issue with birth defects it is most commonly prescribed to males with migraines who are not overweight.

Cymbalta® (duloxetine) or Effexor XR® (venlafaxine)

Effexor XR® and Cymbalta® are both SNRIs. These are medications that raise levels of serotonin (5HT) and norepinephrine (NE) in some synapses. Venlafaxine has been demonstrated in two double blind placebo controlled studies to help prevent migraines at doses of 150 mg per day and above. Duloxetine is more balanced than velafaxine and in animal models of pain, the balance is important in pain relief. Therefore, Dr. Loftus favors duloxetine. They cause equal amounts of nausea but duloxetine appears to be associated with less sexual dysfunction. Cymbalta is FDA approved in depression, anxiety, fibromyalgia, pain from osteoarthritis, and diabetic neuropathic pain. Since 33% to 66% of patients with chronic migraine also have depression, the use of Cymbalta® as a first line agent makes sense for those patients with depression. The cost of duloxetine and venlafaxine ER is about $12 for one month but drops to $6 per month when bought 6 months at a time.


There are studies demonstrating verapamil to be a good anti-migraine agent although not as robust as the medications previously mentioned. It is relatively side effect free so it does have some uses.

The most important thing to remember is that there are numerous agents that one can try for migraine prevention. It is most likely that at least one of them will work well for you. Unfortunately prevention therapies are under utilized, resulting in excessive disability for migraine patients. If you are having frequent headaches, please see your neurologist and ask to be placed on prevention. If you have frequent headaches and are not being offered prevention, then you really need to change physicians.