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IDIOPATHIC INTRACRANIAL HYPERTENSION (IIH) (PSEUDOTUMOR CEREBRI) SYMPTOMS, CAUSES, AND TREATMENTS.

@Neuralgroover

 

What Is Idiopathic Intracranial Hypertension (IIH) (Pseudotumor Cerebri) And What Causes It?

Idiopathic intracranial hypertension (IIH) was previously called pseudotumor cerebri. Pseudotumor cerebri was an old term which was often confusing to patients because this disorder is not because of a brain tumor. Brain tumors in strategic areas of the brain can block the flow of cerebrospinal fluid (CSF), which can cause back up and elevation of CSF pressure, called hydrocephalus. This is where the older term of pseudotumor cerebri was derived from. Benign intracranial hypertension was another previously used term which was changed because the disease can certainly be not so benign.

 

IIH is a completely different problem than the elevated CSF pressure from a brain tumor though, and treated much differently. The problem of IIH involves an elevation of CSF around the brain and spinal cord, without a clear reason.

 

CSF is continuously produced (by something called the choroid plexus inside the ventricles of the brain), absorbed, and transported out of the nervous system (by something called arachnoid villi) and into large draining veins surrounding the brain called the cerebral venous sinuses, and then into the jugular veins and blood where it is broken down.




There have been a number of theories and findings as to the causes of IIH. These include:

 

  • Overproduction of the CSF
  • Blockage of CSF absorption into the cerebral venous sinuses due to a faulty transport mechanism
  • Stenosis (narrowing) of the venous sinuses
  • Blot clot (thrombus) blocking the inside of venous sinuses preventing the outflow of CSF and pressure build up
  • Compression of the venous sinus from the outside (such as brain tumor, meningioma, etc.), causing narrowing on the inside
  • Sex hormones such as androgens and adipose tissue may play a potential role
  • Some medications have been associated with IIH including lithium, retinoids (such as excess vitamin A derivatives), oral contraceptives, and tetracycline antibiotics such as doxycycline and minocycline. Rebound IIH has also been reported from corticosteroid withdrawal.
  • Dural arteriovenous (AV) fistula (an artery connects to the venous sinus, allowing arterial blood flow into the venous sinus and causes much higher pressure)

 

Think of it like this…

 

Imagine the brain and spinal cord surrounded and suspended in fluid called the CSF (which cushions and keeps the brain and spinal cord afloat). To keep this fluid in place, it is surrounded by a thick lining called the dura mater. Basically, think of this arrangement like a water balloon. Now, imagine that you keep filling the water balloon with water until the pressure inside gets higher and higher. Eventually, the balloon pops. The same problem occurs in IIH. The pressure of the CSF gets higher and higher. As the pressure rises, it puts pressure on various areas of the brain and cranial nerves resulting in a variety of neurological and other symptoms. This is the basis of IIH.

Sometimes, the pressure can become high enough and you can get a CSF leak out of the surrounding membrane, similar to the balloon popping. This situation can sometimes lead to a low CSF pressure (intracranial hypotension, or CSF leak), which can cause a different type of positional headache and a different set of symptoms. We’ll discuss the problem of CSF leaks in a separate blog article and will focus here on the problem of high CSF pressure.

 

What Are IIH (Pseudotumor Cerebri) Symptoms?

Headache is the most common symptom of IIH. It typically involves the whole head, and is often worse in the morning (after lying down all night and pressure tends to build). It can commonly flare up by certain activities such as coughing, sneezing, straining, bending forward, and laughing.

 

Normal CSF pressure in adults is generally considered to be 100-200 mm CSF (10-20 cm CSF). According to criteria, IIH consists of a headache associated with CSF pressure greater than 250 mm CSF (25 cm CSF) in adults, and greater than 280 mm CSF (28 cm CSF) in children, checked by lumbar puncture (LP). The CSF pressure should be measured in the absence of treatment to lower intracranial pressure, and without sedative medications. The optimal position to check CSF pressure is lying on the left side (left lateral decubitus position) with legs extended (initially the legs/hips are flexed up towards the stomach for insertion of the LP needle to open up the spaces between the vertebrae, and then can be carefully extended out with assistance once the LP needle is in place), head in neutral position (not flexed far forwards), and the patient is breathing calmly and normally.

 

CSF pressure often varies through the day, so a single measurement may not be indicative of the average CSF pressure over 24 hours. In adults, if the pressure is 200-250 mm CSF (20-25 cm CSF), this can still be considered abnormal if they also have the associated signs, symptoms, and imaging findings consistent with a diagnosis of IIH. If there is uncertainty, prolonged lumbar or intraventricular pressure monitoring is occasionally considered. Temporary relief of the headache following lumbar puncture is often seen and can be supportive of the diagnosis, although it doesn’t confirm or exclude the diagnosis whether it happens or not.

 

IIH criteria also must have at least one of either pulsatile tinnitus (typically described as a whooshing in the ear) and/or papilledema (swelling of the optic nerve (transmits vision to the brain) in the back of the eye, seen during an eye exam).

 

Some patients report transient obscurations of vision (TVOs), which are brief (usually seconds) partial or complete loss of vision which rapidly returns to normal. This is suspected to be due to brief lack of blood flow (ischemia) in the swollen area of the optic nerve (from papilledema). Double vision is occasionally reported. It is usually from abducens nerve (cranial nerve 6) palsy (weakness) and can be 1 or both sides, but other reported nerve palsies can include cranial nerve 3, 4, and 7. Additional symptoms can include neck pain, pain radiating from the neck down the arm (cervical radiculopathy), back pain, ear fullness (such as high altitude), dizziness and unsteadiness.

 

What Tests Are Done To Diagnose IIH (Pseudotumor Cerebri)?

 

Dilated Eye Exam (Fundoscopy)

Irreversible progressive vision loss is the main concern with IIH if it continues untreated. The enlarged physiologic blind spot develops first followed by inferonasal visual defects, followed by progressive constriction of visual fields, and central vision is the last to be affected.

 

Sometimes a subtle clue of elevated CSF pressure can be picked up by observing the venous pulsations in the back of the eye on exam. If they are present, CSF pressure is likely relatively normal. If the venous pulsations are absent, this can suggest elevated CSF pressure. However, occasionally some patients can have a lack of venous pulsations normally. Another normal variant that can appear abnormal is pseudopapilledema. This looks like papilledema, but can also be normal anatomy or from causes such as optic disk drusen. With pseudopapilledema, venous pulsations are usually present, whereas in true papilledema they are absent. Additional tests to evaluate for pseudopapilledema include ultrasound and fundus autofluorescence, done with an ophthalmologist.

 

Every patient with suspected IIH should be referred (preferably) to neuro-ophthalmology to evaluate and monitor for evidence of elevated CSF pressure on a dilated eye exam and full visual field testing. They often do a test called optical coherence tomography (OCT) which is checked periodically to monitor for thinning (atrophy) of the optic nerve, and other structural damage from excess CSF pressure on the nerve. If a neuro-ophthalmologist is not available, than an ophthalmologist (not an optometrist) should be seen. The vision loss from IIH is usually a slow process that may or may not be noticed by the patient, and it is irreversible. Therefore, all IIH patients should have early detailed dilated eye exams and should be followed serially by a neuro-ophthalmologist or ophthalmologist.

 

There are a much less common (and somewhat controversial) group of patients that may have IIH without papilledema. This has been suggested to be possibly related to anatomic variations in the subarachnoid space (where CSF collects around the optic nerve) not reaching far enough to the back of the eyeball. So the part of the optic nerve that may be swollen may be further back behind the eyeball, and can’t be visualized. Another theory of this group of patients includes the episodic presence of a CSF leak, so pressure isn’t sustained long enough to cause papilledema. So, when CSF pressure reaches a certain level, the CSF leaks from a weakened area in the meninges (these keep the CSF in place around the brain and spinal cord) either in the nose (CSF rhinorrhea), the ear (CSF otorrhea), or in the spine. Rarely, some patients are felt to have alternating cycles of high pressure (IIH symptoms) and when the CSF leak reforms, cycles of low pressure (intracranial hypotension, CSF leak headache), so their complaints can vary widely between these 2 extremes of high pressure or low pressure.

 

Lumbar Puncture (LP)

This is really the most central piece of the IIH diagnosis as detailed above. If CSF pressure is high and the patient has signs, symptoms, and/or findings on MRI, then the diagnosis is confirmed. When the LP is done to check pressure, it is worthwhile to also send some CSF to the lab to analyze for signs of inflammation, infection, or cancerous (such as metastatic leptomeningeal disease) factors. Temporary relief of the headache following lumbar puncture is often seen and can be supportive of the diagnosis, although it doesn’t confirm or exclude the diagnosis whether it happens or not.

 

Brain MRI and Brain MRV

A brain MRI with contrast should be a first line test, which helps to exclude other obvious causes of papilledema and elevated CSF pressure (such as brain tumor), and results can support a diagnosis of IIH. However, a diagnosis should never be made based on MRI alone, but on the MRI in combination with a good history and clinical symptoms. Some of the supportive MRI findings include empty sella turcica, or “empty sella syndrome”. However, this is does not definitively confirm the diagnosis, and it is not uncommon to see this appearance in normal patients. Again, putting together MRI findings with the right clinical story is key. Other MRI findings that may or may not be visible include dilation/distention (due to increased CSF surrounding the optic nerves) and tortuosity of the optic nerve sheaths (more curvy and twisted appearance), flattening of the posterior sclerae (flattening of the back of the eyeball), enhancing protrusion of the swollen optic disks, pseudo-Chiari (not a true Chiari, but some cerebellar decent due to high CSF pressure pushing it down), and transverse cerebral venous sinus stenosis (narrowing).

 

Brain MRV should always be done with the MRI to ensure there is no blood clot (cerebral venous thrombosis) in the venous drainage pathways, or significant narrowing (stenosis) of the venous sinuses. It is preferably done with contrast for optimal imaging clarity, although contrast is not absolutely necessary. In most patients, if there is a significant finding, you’ll usually see it on noncontrast MRV. The contrast can add further definition of an area in question if there is uncertainty.

 

How Is IIH Treated?

 

Weight Loss for IIH (Pseudotumor Cerebri)

Weight loss is an absolute must for IIH if the patient is overweight. Research has suggested that losing 6-10% of initial body weight can cause IIH remission in many patients. Bariatric surgery is sometimes considered for morbidly obese patients who are unsuccessful in losing weight by more conservative ways.

 

What is the best IIH (Pseudotumor Cerebri) Diet?

A low-calorie, low-salt diet with mild fluid restriction generally seems to be the most helpful diet for IIH.

 

What Medications Are Used To Treat IIH (Pseudotumor Cerebri)?

The carbonic anhydrase inhibitors are the first line treatment for IIH. These medicines work for IIH because they decrease the production of CSF (and thus CSF pressure is lower because production has slowed). They also have a mild diuretic effect. The most common medications used for IIH are Acetazolamide (Diamox), Topiramate (Topamax), and Methazolamide.

 

Typical doses for Diamox start at 500 mg twice daily and can be increased to 2000 mg twice daily, although lower doses are often effective. Side effects can include tingling/numbness (paresthesias), changes in taste, and gastrointestinal symptoms such as nausea, vomiting, or diarrhea.

 

If there is any question of migraine mixed in with IIH, then Topiramate is my first choice because it is also FDA approved for migraine prevention, in addition to decreasing CSF production. I usually start Topamax with 25 mg at bed and is increase by 25 mg at bed each week until 100 mg at bedtime. If not improving by 4 weeks at the 100 mg dose, morning dosing is then added with 50 mg for 1 week and then 100 mg twice daily. Side effects often include weight loss, which would certainly be a desired side effect in obese patients with IIH. Other side effects can include mood changes, tinging/numbness, and cognitive complaints such as memory, word finding, and concentration.

 

Methazolamide is started at 25 mg twice daily and can be increased to 200 mg twice daily.

 

Other medicines sometimes used if the above options are not tolerated or working include furosemide and bumetanide. For sulfa allergic patients, spironolactone, triamterene, and ethacrynic acid are occasionally used.




Treating Other Headache Disorders That Occur With IIH (Pseudotumor Cerebri)

It is also very important to also treat other headache disorders that may be mixed in with the IIH headaches. For example, many patients with IIH also have headache flares that easily fit criteria for migraine headaches. They typically have chronic daily headache which looks like a mix of chronic migraine and chronic tension type headache. So, when there is IIH mixed in with these headache disorders, it sometimes becomes cloudy on which headache disorders are contributing to which symptoms as well as the overall chronic daily headache. Many times these patients are in rebound headache (medication overuse headache), and that issue must be treated and resolved before the headaches are able to improve. I typically treat these patients targeting both chronic migraine and IIH (if IIH has been confirmed as well) since they are most often intermingled.

 

If there are any associated headache symptoms of throbbing, pulsating, pounding (even if a low level), nausea, sensitivity to both light and sound with headache flares, then migraine should also be targeted with both an abortive and preventive treatment option. Abortive options include NSAIDs, ergots, triptansneuromodulatory devices, the ditans (Reyvow (Lasmiditan)) and the gepants (Ubrelvy (Ubrogepant) and Nurtec ODT (orally dissolvable tablet) (Rimegepant)).

 

If the migraines are happening frequently enough, then a migraine preventive treatment should be considered. Preventive migraine treatments are used to lessen the frequency and/or severity of migraine attacks. Preventive treatments include a variety of daily pill medicationsCGRP monoclonal antibodies (mAbs) (Aimovig (Erenumab), Emgality (Galcanezumab), Ajovy (Fremenazumab), Vyepti (Eptinezumab)), neuromodulation devicesBotoxNurtec ODT every other day (1st and only dually approved migraine abortive and preventive), herbal and natural supplements and vitaminsyoga and meditation, and acupuncture and acupressure.

 

What Are Surgical Treatments for IIH (Pseudotumor Cerebri) When Other Treatments Fail?

 

Optic Nerve Fenestration For IIH

Optic nerve fenestration is sometimes done for papilledema that is not improving with standard medical treatments and vision continues to worsen. This is basically a procedure which makes small slits in the optic nerve sheath, which encloses the optic nerves and keeps the CSF in place around them. By doing this, it can release the CSF pressure on the nerves (imagine it as cutting a slit in a garden hose). This procedure is only done to prevent further vision loss which isn’t responding to conservative treatment, but does not typically help the headache.

 

Venous Sinus Stenting For IIH

Stenoses of the transverse venous sinuses can sometimes be seen on MRV. This leads to increased venous pressures in these channels, as well as the superior sagittal sinus. Increased venous sinus pressures can be confirmed with catheter venography with manometry. Transverse venous sinus stenting is occasionally considered as a surgical treatment option for IIH in patients with pressure gradients of more than 8 mm Hg and refractory symptoms. One study found that a pressure gradient of 21 mm Hg or higher had the best outcomes.

 

Shunts for IIH

Ventriculoperitoneal (VP) shunts and lumboperitoneal (LP) shunts are occasionally done with a goal of surgically placing a valve and tubing device to maintain a normal pressure in the spinal fluid. VP shunting is preferred over LP shunting due to lower rates of complications. If the pressure reaches above a specific pressure setting of the valve, then CSF will drain through the tubing and into the peritoneal cavity of the body where it is then absorbed and eliminated. Shunting should always be a last resort option (outside of severe emergent cases which need rapid pressure relief) after every possible medical management option has failed. Shunts don’t tend to provide long term effectiveness for headache management and frequently require revisions. It is not uncommon for the hardware to become infected or blocked and then have to be removed. One large study found that initial improvement in headaches following shunting returned to recurrent headaches at 36 months in almost half of all patients.

 

How Do You Treat IIH (Pseudotumor Cerebri) In Pregnancy?

Acetazolamide can be used after the 1st trimester. Repeated LPs to drain some of the CSF pressure can be done if necessary. For women who have progressive papilledema and worsening vision, optic nerve fenestration may be necessary to preserve vision, although it will not typically help the headache.




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Last updated on September 17th, 2021 at 06:40 am

BEST HEADACHE AND MIGRAINE PREVENTION MEDICATIONS AND TREATMENTS, WHEN YOU SHOULD START ONE, AND WHEN YOU SHOULD STOP IT.

@Neuralgroover

BACKGROUND

Migraine is a very disruptive disorder to have to deal with. It interferes with patients’ family, work, and social lives. When the burden of migraine becomes excessive on one or more of these life aspects, preventive migraine therapy should be used. In general, if someone is averaging more than 4 migraines per month, preventive treatment should be offered and discussed, although this number is not an absolute. For example, if someone has 1 migraine per month, but it wipes them out for 1 week and they are missing work, there are certainly variations on when preventive medications should be considered, such as this scenario. If the decision to use a preventive migraine medication has been made, there are several important factors to keep in mind in order to optimize treatment success, as discussed below.

So this blog will focus on migraine preventive meds and treatments, which are a continuous treatment such as a daily pill or a monthly/quarterly treatment such as CGRP mAbs, all of which are detailed below. The goal of migraine preventive treatment is to lessen the frequency and/or severity of migraine attacks. This is in contrast to migraine abortive/acute (as needed) options such as triptans, gepants and ditans. The goal of migraine abortive treatments is to stop individual migraine attacks at onset so the migraine does not reach full severity, ends quickly, and your function is restored and maintained rather than having to go lay down and miss the whole day in bed.  If you have migraine, you want to have both a good abortive and preventive treatment plan to lessen migraine’s nasty habit of interfering and disrupting life and function.

 

TIME

Any preventive medication needs an adequate “therapeutic trial”. In short, you need to be patient and give it enough time to work, as well as get to the correct dose. I see patients all the time that tell me their doctor put them on a medication (usually at too low of a dose), and they stopped it after 3 weeks because it “wasn’t doing anything”. Well, it’s not going to do anything that soon, and that is too early to expect any significant improvement. In general, any preventive medication needs 4-6 weeks to begin working, and 2-3 months until full effect is seen (assuming a good dose has been reached). A good rule of thumb is evaluation of response a minimum of 8 weeks after reaching a target therapeutic dose. If there is a partial response at that time, it’s possible that cumulative benefit can continue to occur over 6-12 months. So the decision on whether to continue really depends on how much benefit has been received, and how well the the patient is tolerating the medication. Unfortunately, there is no way to expedite this process. That doesn’t mean the treatment can’t work sooner. However, that is the standard duration of treatment for a medication to have had a fair trial. Finding a migraine preventive is often a trial and error process. If a treatment is not starting to help by at least 8 weeks at a good dose, changing to a different therapy is suggested. However, once an effective treatment is found, the wait is well worth the decline of migraine frequency and severity!

 

DOSE

In addition to an adequate trial duration, an adequate trial dose is also necessary. For example, a common first line medication used for migraine prevention is Topiramate (which is also FDA approved for migraine prevention). I often see patients who come in on 25 mg or 50 mg and have been on that dose for a year or more without much benefit. I discuss with them that the goal dose is at least 100 mg total daily dose, so the dose is too low. For example, in the migraine preventive trials, once patients reached 100 mg and had been at that dose specifically for at least 4 weeks, that is when improvement of statistical significance began. So, I typically start 25 mg at bedtime for 1 week. Then each week increase by 25 mg at bedtime until 100 mg is reached, and then I give a 100 mg pill to begin. I tell them if there is no improvement starting after at least 4 weeks from reaching the 100 mg dose specifically, let me know. I usually dose it all at bedtime which can help limit side effect potential (since you’ll be sleeping). However, it is generally meant to be taken as a twice daily medicine (such as 50 mg twice daily), and most patients tolerate that fine too.

 

With that said, patients can certainly respond to low doses of medications. However, if improvement has been minimal after a month of a lower dose, it is always a good idea to begin titration up to a better dose. The American Headache Society and American Academy of Neurology published guidelines of migraine preventive medications which includes common goal dose targets for some of these preventive medications here.

 

TREATMENT SELECTION

There are many preventive treatments used, although most of them are considered “off-label” for migraine prevention. This means they are not actually FDA approved for migraine prevention, but there is enough evidence based on research trials or clinical experience to warrant them as a valid option to try. As far as true FDA approved oral (pills by mouth) preventive medications, there are 4 available that have this distinction; Topiramate, Divalproex, Propranolol, and Timolol. There are also a number of natural migraine treatments with supplements which have evidence for migraine prevention, and those are detailed and discussed here.

 

So, let’s discuss migraine prevention medicine.  The categories of oral preventive migraine medications all sound bizarre. They consist of anti-seizure (anti-convulsant), anti-depressant/anti-anxiety, and anti-hypertension (blood pressure) medications. It is important for patients to know that the medicine is being used specifically for migraine. I often see patients who say they didn’t start the medicine their doctor prescribed because they got home, Googled it, and they tell me, “I’m not depressed”. I explain the reasoning for the medication and that it is not for depression, but for migraine prevention since there are overlapping electrical pathways between many of these types of disorders. Furthermore, there are select medications within each of these categories that have evidence from trials and clinical experience for migraine prevention, as listed here and here. For patients that have chronic migraine (15 or more headache days per month with 8 or more days having migrainous features), Botox is another highly effective option to consider.

 

It is also important to know that the medications in each of these medication classes are not a “one size fits all” for every medicine within that category. For example, there is no good evidence for migraine prevention in the SSRI (selective serotonin reuptake inhibitors) anti-depressant/anti-anxiety medication category (Fluoxetine, Sertraline, Escitalopram, Citalopram, etc.). However, there is evidence for benefit in some of the SNRIs (serotonin and norepinephrine reuptake inhibitors) such as Venlafaxine XR, Duloxetine, as well as some of the TCAs (tricyclic antidepressants), primarily Amitriptyline and Nortriptyline. Similarly, there are select medications within the anti-seizure/anti-convulsant category which have the best evidence (Topiramate, Divalproex), as well as the anti-hypertension category (Propranolol, Metoprolol, Atenolol, Nadolol, Verapamil).

 

There are now 4 monoclonal antibody CGRP receptor antagonists which have this FDA approval for migraine prevention also. Three of them are once monthly auto/self-injections (Aimovig, Ajovy, Emgality), and one is a once quarterly (every 3 months) 30 minute IV (intravenous) infusion (Vyepti). In general, these are an option for those with 4 or more migraines per month on average.  The great thing about these treatment options as opposed to standard pill options is that they do not require a gradual dose escalation, they tend to have a much more rapid onset of improvement, and they have very low side effect risk. These medications are all discussed in much greater detail and comparison here.

 

Neuromodulatory devices that are FDA cleared for migraine prevention are also available and include sTMS (SAVI, SpringTMS, sTMS mini),  eTNS (CEFALY), and nVNS (GAMMACORE), all of which are discussed in much greater detail here. There are also nutraceuticals and supplements which have good evidence for migraine prevention. Yoga, relaxation and wellness therapies are also helpful in migraine prevention.

 

An exciting development is that there are 2 migraine preventive medications in the new gepant classification which are currently in clinical trials, and showing good evidence of effectiveness. They are both oral pills and include Atogepant and Rimegepant (currently FDA approved for abortive migraine treatment under the name Nurtec ODT 75 mg). So these will open up another new class of preventive migraine medications engineered purely for migraine treatment! Notably, Biohaven submitted a request to the FDA in October 2020 to approve Rimegepant as a preventive migraine treatment, in addition to its current migraine abortive FDA approved indication. On 5/27/21, Nurtec ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility! This new dual abortive and preventive therapy option can be read about in more detail here This move followed clinical trials showing that patients taking 75 mg of Rimegepant every other day experienced a 4.3 day reduction from baseline in monthly migraine days.

 

When choosing a preventive treatment, I like to fine-tune the treatment to “hit as many birds with one stone”. In other words, pick something that will not only help with migraine prevention, but may also help with other medical conditions at the same time. Doing this can allow you to help minimize the number of medications used overall, by using something with benefit for several disorders in addition to the migraine. For example, if someone has depression or anxiety, targeting their migraine preventive medication with an anti-depressant/anti-anxiety category would make sense. If the patient has other chronic musculoskeletal pain issues, fibromyalgia, occipital neuralgia, etc., the SNRIs and the TCAs are good considerations. If the patient has insomnia, Amitriptyline or Nortriptyline are great options. If they have seizures, an anti-seizure medication such as Topiramate or Divalproex would make sense. If they are overweight, Topiramate also causes weight loss. Divalproex is another anti-seizure medicine which is also FDA approved for migraine prevention. However, this should be avoided when possible in young women of child-bearing age given the high risk of congenital birth defects while taking it (and most pregnancies are unplanned).

Here are some treatment considerations to take into account for migraine preventive therapy in addition to the following medical conditions the patient may also have:

-Obese/Overweight: Topiramate (Topamax), Topiramate ER/XR (extended release, Trokendi or Qudexy XR), Zonisamide  (Zonegran): All can cause weight loss, which can be helpful in overweight patients. However, use with caution if patient is extremely thin to limit further weight loss. If they improve with Topamax, but have Topamax side effects (numbness and tingling, word-finding difficulty, speech disturbances, memory and cognitive disturbances, mood changes), changing to Topiramate ER/XR (extended release) or Zonisamide tend to have similar benefit with less side effects. Women who are on oral contraceptive pills are often warned prematurely by their pharmacist that Topiramate will effect their oral contraceptive. This is partly true. Topiramate at a daily dose of 200 mg or less does not interact with oral contraceptives according to this study, but it can at higher doses which could potentially decrease effectiveness. However, the goal dose for effective migraine prevention is typically 100 mg per day, well below that 200 mg dose that could impact effectiveness of the oral contraceptive. I would avoid Amitriptyline, Nortriptyline since there is a risk of weight gain for some.

-Underweight/Excessively thin: Side effects of Nortriptyline and Amitriptyline can occasionally be weight gain (but not necessarily), but this may be beneficial in some patients.

-Depression and/or anxiety: Venlafaxine ER, Duloxetine, Amitriptyline, Nortriptyline, Desvenlafaxine

-Mood disorder such as bipolar or psychosis: Divalproex, Topiramate, Carbamazepine

-Anxiety without depression: Venlafaxine ER, Amitriptyline, Duloxetine, Nortriptyline, Desvenlafaxine, Propranolol

-Insomnia: Amitriptyline, Nortriptyline

-Fatigue/Low energy: Venlafaxine ER, Duloxetine (these can be energizing for many, so are best taken in morning)

-Hypertension: Propranolol, Metoprolol, Nadolol, Atenolol, Lisinopril, Candesartan, Verapamil

-Palpitations: Propranolol, Metoprolol, Nadolol, Atenolol

-Chronic musculoskeletal pains, fibromyalgia, neuropathy/nerve pains: Amitriptyline, Duloxetine, Nortriptyline, Gabapentin

-Pregnancy: This one is tricky since the goal during pregnancy is to minimize the use of as many medications as possible. Mindfulness treatments such as yoga and meditation are always good recommendations. With that said, the first line option we typically begin with is magnesium supplementation of 400-800 mg daily. If a prescription medication is needed, cyproheptadine 4 mg at bedtime has been a long time medicine used in this scenario, and it can be titrated to 4 mg three times daily if needed. The good thing with pregnancy is that migraines improve in about 2/3rd of women (especially 2nd and 3rd trimester), and it is not uncommon to hear that migraines resolved during pregnancy. So many times a preventive treatment may not even be needed. For menstrually related migraine outside of pregnancy, further discussions and treatment considerations can be read here.

-Epilepsy: Topiramate, Topiramate ER/XR (extended release), Divalproex, Carbamazepine, and Zonisamide are the anticonvulsant medications we see most useful for migraine prevention. In fact, Topiramate and Divalproex are also FDA approved for migraine prevention. If patients improve with Topiramate but have side effects, changing to Topiramate ER/XR (extended release) or Zonisamide tend to have similar benefit with less side effects. Women who are on oral contraceptive pills are often warned prematurely by their pharmacist that Topiramate will effect their oral contraceptive. This is partly true. Topiramate at a daily dose of 200 mg or less does not interact with oral contraceptives according to this study, but it can at higher doses which could potentially decrease effectiveness. However, the goal dose for effective migraine prevention is typically 100 mg per day, well below that 200 mg dose that could impact effectiveness of the oral contraceptive.

-Non-oral route needed or preferred: Once monthly self/auto injections of monoclonal antibody CGRP receptor antagonists (Aimovig, Ajovy, Emgality) or once quarterly 30 minute IV infusion (Yvepti), which are all detailed here. Botox is another non-pill option for those averaging 15 or more headache days per month with at least 8 of those days having any migrainous features (throbbing, nausea, sensitivity to light (photophobia) or sound (phonophobia)) for 3 or more consecutive months (chronic migraine). Neuromodulatory devices that are FDA cleared for migraine prevention are also available and include sTMS (SAVI, SpringTMS, sTMS mini),  eTNS (CEFALY), and nVNS (GAMMACORE), all of which are discussed in much greater detail here.

-Averaging 15 or more headache days per month with at least 8 of those days having any migrainous features (throbbing, nausea, sensitivity to light (photophobia) or sound (phonophobia)) for 3 or more consecutive months (chronic migraine): Botox (Onabotulinumtoxin-A) injections every 3 months according to the PREEMPT chronic migraine treatment protocol. This is the only truly FDA approved medication for prevention of chronic migraine as of 2010. Any of the above listed medications are also options to consider, and most insurances will require failure of at least 2 classes of preventative oral medications before Botox is approved anyway, but this varies by insurance.

 

EXPECTATIONS

Expectations in migraine management are important. If your expectation is that your migraines will stop completely when you use preventive medications, you will be sorely disappointed. Of course it can certainly happen, but that is rare and should never be the expectation or goal. The goal of preventive therapy is a decrease in migraine frequency and/or severity of attacks (optimally both) to some extent to make them more tolerable and less intrusive into life. A general goal is 50% improvement in frequency and/or severity. Some patients can get much more than that, while others get much less (which would signal trials of a different medication class). With that said, success with migraine preventive benefit can also be considered in significant decreases is migraine attack duration or severity, reduction in migraine associated disability, improving the patient’s functioning in various areas of life, improvements in quality of life, and improvement in acute treatment responses. In general, studies estimate that about 45% of patients on conventional preventive therapy (such as oral medications) receive 50% reduction in monthly migraine days. Thus, 55% will receive less improvement than this. The CGRP mAbs tend to have a higher rate of improvement then conventional treatments as detailed here.

 

WHEN TO STOP

There is no absolute answer of when to stop preventive therapy. It depends on how well one is doing, how long they have been doing well, and how much they want to get rid of treatments. Some people want off as soon as they can, others prefer to stay on for years since they are doing very well with few migraines, and don’t want to “rock the boat”. In general, the goal is to continue preventive therapy until the patient is doing significantly better for at least 3 months, but preferably closer to 6 months or so. I always make sure to tell patients that preventive medicines or treatments are not necessarily meant to be a life-long commitment. Rather, we use these treatments to “reboot” and “reset” the brain’s electrical system to have less frequent and/or severe migraines, and then try to sneak away off the medications once they are consistently doing better.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

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