injections | Headache NewsBlog

Botox relieves hemiplegic migraine and migraine with aura

By: Dr. Mauskop

22-09-2018

Botox, Chronic migraine, injections, Migraine

A recent report by neurologists from the Mayo Clinic suggests that onabotulinumtoxinA (Botox) injections can relieve not only headache pain, but associated neurological symptoms, such as visual aura, numbness and weakness, which can precede or accompany a migraine attack. This article describes 11 patients with hemiplegic migraine, which means that these patients developed weakness on one side of their body prior and during an attack. From the description of these cases, it appears that at least a couple of patients had migraine with sensory-motor aura rather than true hemiplegic migraine. But regardless of the precise nature of their symptoms, Botox was effective in reducing these symptoms, along with headaches in 9 out of 11 patients. Ten of the 11 patients had chronic migraine and on average they failed five preventive drugs before starting Botox.

Two of the physicians who wrote the report have already presented some of these cases in 2013. As mentioned in the blog post describing this older report, I have also successfully treated many patients with visual, sensory and motor aura with Botox injections. Just like with patients in the current article, many of my patient responded to Botox after failing several preventive drugs.

We seem to understand how Botox relieves pain, but it is less clear how it helps neurological symptoms such as weakness, numbness and visual impairment. One possible explanation is that Botox reduces painful messages from the surface of the skull to the brain, which reduces excitability of the brain and this in turn prevents the brain from generating a migraine attack, including its associated symptoms.

Breakthrough in the treatment of migraines

By: Dr. Mauskop

08-12-2017

Cluster headaches, injections, Migraine, New treatments

Two landmark studies on an entirely new type of treatment for migraines have been just published in the New England Journal of Medicine.

One of the reports describes a phase 3 trial (final phase that can lead to the FDA approval), which was conducted by Teva Pharmaceuticals using a monoclonal antibody, fremanezumab to treat patients with chronic migraine (patients with 15 or more headache days each month). The study involved 1,130 patients who were divided into three groups: one group received monthly injections (subcutaneously, i.e. under the skin) of the active medicine, another group was given an injection of the real medicine every 3 months and placebo injections monthly in between, and the third group received placebo injections every month. Patients in both groups that received real shots did much better than those given placebo. They had fewer days with headaches, used less of the abortive migraine medications, and had a lower impact of migraines on their lives. The effect of the drug lasted 3 months, which suggests that one injection every three months will be sufficient. We also hope that patients will be able to inject themselves and not have to come to doctors’ offices every month. The side effects were mostly related to the injection itself – pain, swelling, and bruising.

The second study conducted by Amgen and Novartis utilized a similar drug, erenumab (it will have the brand name of Aimovig when it becomes available in the middle of next year) to prevent episodic migraines, that is migraines that occur on fewer than 15 headache days each month. A total of 955 patients participated in this study and they were also divided into three groups: those receiving either 70 or 140 mg of medicine and a group receiving placebo. Injections were given monthly to prevent migraine attacks. Both doses of the drug resulted in significantly fewer migraine attacks and improvement in physical impairment and everyday activities. Side effects were mostly due to the injection site reactions, just like with fremanezumab.

Both fremanezumab and erenumab belong to the family of CGRP monoclonal antibodies, drugs that block a neurotransmitter CGRP which is released during a migraine attack. Two additional companies, Eli Lilly and Alder are developing similar drugs, galcanezumab and eptinezumab, which are also expected to be approved next year. Eli Lilly’s drug is also being tested for the prevention of episodic cluster headaches.

I first wrote about the CGRP drugs in a blog post in 2007, more than 10 years ago. At that point CGRP was the target of research for over 10 years, so in total, it will have taken 20 years to bring these new drugs to the market. It was even longer with triptans, such as sumatriptan (Imitrex) – it took 30 years since the discovery of the potential role of serotonin to the approval of sumatriptan. The drug development process takes not only decades of time, but also billions of dollars, which explains why new drugs are so expensive, at least in the first few years. After years of being on the market, prices of drugs tend to go down and now 90 tablets of sumatriptan can be bought for $70 at Costco, while similar branded triptan drugs used to cost $40 for a single tablet.

Sumatriptan injections still underutilized. New lower dose, easy-to-use device could help

By: Dr. Mauskop

30-07-2017

Headache medications, injections, Migraine

Sumatriptan (Imitrex) injection was introduced 25 years ago, but it remains extremely underutilized. Of course, why would you inject yourself if a pill does the job. Unfortunately, for many migraine sufferers sumatriptan and other triptan tablets do not provide complete or fast enough relief. In many patients tablets do not work well because some wake up with a severe migraine, in some it starts very suddenly, and in others it is accompanied by nausea and vomiting. All these conditions require a quickly acting drug that bypasses the stomach. Zolmitriptan (Zomig) and sumatriptan nasal sprays or sumatriptan nasal powder (Onzetra) sometimes work well and quickly enough, but the gold standard in the abortive treatment of migraines (and cluster headaches) is sumatriptan injection.

Sumatriptan injection works within 10-15 minutes and often provides complete relief of the headache and associated symptoms – nausea, sensitivity to light and noise, and other. Because of a sudden surge in the sumatriptan level in the blood, side effects are more common than with tablets. These can include pins-and-needles like sensations, tightness in the neck or chest, or temporary worsening of the headache. These side effects last only 15-20 minutes and do not prevent most patients from using injections.

Sumatriptan injections were originally released only in a 6 mg dose. A few years later, 4 mg dose became available. Last year, a simple-to-use autoinjector with 3 mg of sumatriptan (Zembrace) was approved by the FDA. Studies presented at the recent annual meeting of the American Headache Society in Boston compared the efficacy of 3 mg and 6 mg injections. Surprisingly, they were equally effective and well tolerated. The manufacturer of the 3 mg auto-injector also compared their injection device with two older devices. Findings of this study were not a surprise – Zembrace was easier to use with fewer mistakes and faster preparation and administration. Zembrace requires only two steps – pulling off a cap and pressing the pen-like device against the thigh (and holding it pressed for 10 seconds). Also, of all auto-injectors Zembrace has the thinnest needle.

One potential difficulty is the insurance coverage. Since Zembrace is more expensive, the insurers may offer to pay only for the old type devices with 4 or 6 mg of sumatriptan. The manufacturer does offer discounts and coupons, which you can find online.

The bottom line, if you are not getting good relief of your migraine headaches, ask your doctor about sumatriptan injections. If you have tried injections in the past and did not like the side effects – check if the dose you tried was 6 mg and if yes, you may want to try 3 or 4 mg injections.

Sumatriptan injection is the only FDA-approved treatment for cluster headaches. Cluster headaches are very sudden and brief attacks of excruciating headaches that pills rarely have a chance to control.

Conflict of interest disclosure: last year Zembrace manufacturer paid me to participate in an advisory board meeting.

How to reduce the cost of Botox for migraines

By: Dr. Mauskop

24-01-2017

Botox, injections, Migraine

Botox is by far the safest and the most effective preventive treatment for chronic and frequent episodic migraine headaches. The only downside is the cost. A 200-unit vial of Botox costs about $1,200. Most insurance companies cover Botox if you have chronic migraines (15 or more headache days each month) and if you’ve tried and failed (it did not help or caused side effects) 2 or 3 preventive medications. The copay for a vial of Botox is often as high as $400 or more. If your insurance does not cover Botox at all, or you have “only” 10 to 14 headache days each month, or you do not want to take daily drugs because of potential side effects, you may have to pay the entire cost. To reduce this cost, you may want to ask the doctor to start with 100 units instead of the standard dose of 155 units. Since the manufacturer makes only 100 and 200 unit vilas, the remaining 45 units are discarded. Some doctors are very accommodating, but I’ve heard of many that will not deviate from the FDA-approved protocol of 155 units injected into 31 spots. I discussed some of this in a recent post.

Another way to avoid excessive costs when paying out of pocket for Botox is to avoid large hospitals. A few years ago, while giving lectures at the Mayo Clinic, Cleveland Clinic, and Beth Israel Hospital in Boston, I discovered that they all charged $6,000 for one Botox treatment. What prompted this post is that I recently saw a patient who had Botox injections at the Cedars-Sinai Hospital in Los Angeles and had to pay $11,000. Every charge for a procedure done in a hospital or even at a doctor practice that is owned by the hospital, includes a hefty “facility fee”. This is why hospitals often buy doctor practices – they can triple the charges and even insurers such as Medicare and Medicaid will pay at an inflated rate.

Magnesium in pregnancy

By: Dr. Mauskop

18-05-2016

Alternative Therapies, injections, Migraine

Intravenous magnesium infusions may not be as safe in pregnant women as it has been always thought. The FDA recently moved intravenous magnesium from category A into category D (see category definitions below). This came about after the FDA reviewed 18 cases of babies who were born with serious problems after their mothers received intravenous infusions of large amounts of magnesium for 5 to 7 days in order to stop premature labor. The FDA strongly discourages this practice and states that “Administration of magnesium sulfate injection to pregnant women longer than 5-7 days may lead to low calcium levels and bone problems in the developing baby or fetus, including thin bones, called osteopenia, and bone breaks, called fractures.”

However, treatment of choice for eclampsia remains intravenous magnesium. Eclampsia, one of the most serious complications of pregnancy can be treated only with high doses of intravenous magnesium. Without intravenous magnesium eclampsia can lead to epileptic seizures, very high blood pressure, kidney failure and death.

The FDA also recommends that “Magnesium sulfate injection should only be used during pregnancy if clearly needed. If the drug is used during pregnancy, the health care professional should inform the patient of potential harm to the fetus.”

We do treat many patients, including pregnant women, with intravenous infusions of magnesium if they are deficient in magnesium and if their migraines respond to such infusions. Typically, these infusions are given monthly and the amount is only 1 gram, while for preterm labor the dose is 4-6 grams to start and then 2-4 grams an hour as needed. This monthly dose of 1 gram is extremely unlikely to cause any adverse effects. We find that migraines triggered by magnesium deficiency do not respond well to any other treatments and considering the risk of drugs, it is much safer to administer 1 gram of magnesium. This amount of magnesium just corrects the deficiency and does not cause very high magnesium levels, which can be detrimental.

Several other drugs routinely used in pregnancy may also not be as safe as we thought. Acetaminophen (Tylenol) has been considered one of the safest choices. However, recent evidence suggests possible link to attention deficit disorder with hyperactivity (ADHD).

Butalbital, which is an ingredient in the popular headache drugs such as Esgic, Fioricet and Fiorinal is associated with an increased risk of congenital heart defects. Fioricet also contains caffeine, which has negative effects on the fetus and which can cause rebound (medication overuse) headaches.

FDA drug categories in pregnancy

Category A
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Example drugs or substances: levothyroxine, folic acid, liothyronine

Category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Example drugs: metformin, hydrochlorothiazide, cyclobenzaprine, amoxicillin, pantoprazole

Category C
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: tramadol, gabapentin, amlodipine, trazodone, prednisone

Category D
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: topiramate (Topamax), divalproex sodium (Depakote), lisinopril, alprazolam, losartan, clonazepam, lorazepam

Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Daily long-term use of sumatriptan injections in cluster headaches

By: Dr. Mauskop

07-02-2016

Cluster headaches, Headache medications, injections

My most commented on blog post (over 150 comments) is on the daily use of triptans. A new report confirms the safety of long-term daily use of sumatriptan injections in cluster patients. Cluster headaches are arguably the most severe type of headaches and the name comes from the fact that they tend to occur in clusters lasting several weeks to several months. However, in some patients headaches become persistent without any remissions and then they are called chronic cluster headaches. The only FDA approved treatment for cluster headaches is injectable sumatriptan (Imitrex). Most patients have one cluster attack in 24 hours, but some have many. A report mentioned in one of my other previous blogs describes a woman (although men are more commonly affected by cluster headaches) who has been injecting sumatriptan daily on average 20 times a day for 15 years.

A recent report by Massimo Leone and Alberto Cecchini is entitled, Long-term use of daily sumatriptan injections in severe drug-resistant chronic cluster headache.

The authors investigated occurrence of serious side effects in patients with chronic cluster headaches who were using sumatriptan injections continuously at least twice daily (the official limit) for at least 2 years. They found fifty three such patients with chronic cluster headaches seen in their clinic between 2003 and 2014. During the 2-year period, all patients were carefully followed with regular visits at their center. Headaches and sumatriptan consumption were recorded in headache diaries. Patients were questioned at each visit about serious side effects and had at least two electrocardiograms. Brain MRI was normal in all patients. None of the patients had a history of stroke, TIA, ischemic heart disease, myocardial infarction, or arrhythmia, or diseases affecting systemic vessels.

In the 2-year study period, no serious side effects were observed and no patients needed to discontinue sumatriptan use. No electrocardiogram abnormalities were found. All patients needed a full dose (6 mg) of sumatriptan injection (prefilled syringes with 4 and 6 mg available). At the end of the study period, 42% noticed some reduction in the efficacy of sumatriptan injections both in terms of time of onset of effect and on pain intensity, but still considered the drug their first choice to treat the attacks.

In the study period, 36 of the 52 patients (69%) used more than 12 mg of sumatriptan in 24 hours (maximum 36 mg in 24 hours) but no increase in number or severity of side effects was observed during the course of the study. Complete loss of efficacy was not reported by any of the patients.

The authors mention that since the launch of sumatriptan injections in 1992 and until 1998, approximately 451 serious cardiac side effects have been reported to occur within 24 hours after administration of sumatriptan injections, tablets or nasal spray, but this is out of more than 236 million migraine attacks and more than 9 million patient exposures between 1992 and 1998. The majority of patients who developed serious cardiac events within 1 to 3 hours of sumatriptan administration had risk factors for coronary artery disease.

The authors concluded that their results showed that long-term daily sumatriptan use in patients free of heart disease did not cause serious side effects and this is in line with observations from previous studies.

About my migraines

By: Dr. Mauskop

09-11-2015

Blocks, injections, Migraine

Since my early 20s I’ve been getting visual auras without a headache several times a year. I still get them in my late 50’s and they still occur without a headache. In my 40s I started to have migraine headaches without an aura. My migraines are always left-sided and if I don’t treat them, I will develop sensitivity to light and nausea. Luckily, my migraines are not at all disabling because they remain mild for hours, so I have plenty of time to take 100 mg of sumatriptan, which works very well. The tablet works within one to two hours. When I want to have faster relief, I take a 6 mg sumatriptan injection. This usually happens at night when I want to go to sleep and I don’t want to wait for the pill to start working. I can’t fall asleep with a migraine, while for some, sleeps actually relieves the attack.

I am not happy about having migraines, but they do not interfere with my life and give me a better understanding of what my patients are going through. Also, I try to subject myself to treatments I offer my patients. I do not need to take a daily preventive medicine, such as topiramate or propranolol or Botox injections. However, since Botox is very safe, I did inject myself with Botox once to see what it feels like. It was not very painful, but obviously everyone has a different pain threshold (here are video 1 and video 2 of me injecting patients with Botox). I also gave myself an intravenous infusion of magnesium, which did make me feel warm, but had no beneficial effects since I am not one of the 50% of migraine sufferers who are deficient in magnesium.

The next thing I decided to try is a nerve block. Nerve blocks are injections of a local anesthetic, such as lidocaine or bupivicaine to numb the nerves around the scalp (here is a previous blog on nerve blocks). It is somewhat surprising that numbing a superficial nerve under the skin stops a migraine, which we know to originate in the brain. For the same reason a lot of scepticism greeted me at medical meetings over 20 years ago when I gave lectures on Botox for migraines. Now we know that although the migraine process begins in the brain, peripheral nerves send messages back to the brain closing a vicious cycle of brain activating the nerves and nerves feeding back pain messages into the brain. Disrupting this circuit with a peripheral nerve block for short-term relief and with Botox for long-term prevention seems to be very effective. Nerve blocks can be effective when drugs are not or when drugs are contraindicated because of an illness or pregnancy.

Sometimes, blocking the occipital nerve at the back of the head works well, but other patients need nerves blocked in their temples or forehead. Since my migraines are always localized to the left temple, I decided to give myself a block of the temporal branch of the left trigeminal nerve. The nerve block helped one of two times I tried it. Obviously, I do not recommend DIY nerve blocks or teach patients how to do it, but I did encounter one patient who learned how to give himself an occipital nerve block before coming to see me. There might be some exceptions, such as for people living in remote areas and who do not respond to any other treatments, or in not such distant future, for those traveling to Mars.

The next treatment I will try is a sphenopalatine ganglion block. I will describe this treatment in my next post.

If you migraine requires injectable medicines, decline intravenous Benadryl

By: Dr. Mauskop

06-07-2015

Headache medications, injections, Migraine

Hopefully, your doctor has given you many treatment options, so that you can manage even the most severe attacks at home (including Compazine or Phenergan anti-nausea suppositories for when you are very nauseated or vomit and Imitrex or sumatriptan injection pen for severe pain). However, many people end up in an ER, where they are usually given an injection or intravenous medications. Unfortunately, there is no standard protocol for the best way to treat an acute migraine that does not respond to oral medications. Ideally, the first step should be an infusion of magnesium, which can provide fast relief for up to 50% of patients. Some ER doctors give an injection of sumatriptan or a non-narcotic pain killer ketorolac (Toradol). Others will give a nausea drug which can also help pain such as metoclopramide (Reglan) or prochlorperazine (Compazine). An allergy medicine, diphenhydramine (Benadryl) is also a popular choice.

A study by Dr. Benjamin Friedman and his colleagues at the Albert Einstein COllege of Medicine in the Bronx compared the efficacy of intravenous Reglan combined with Benadryl and Reglan without Benadryl. This was a double-blind study, meaning that neither the doctor giving the medicine nor the patient knew what was being given. They recruited 208 patients, which is a high enough number to produce reliable results. And the results showed that Reglan without Benadryl provided as much relief as with Benadryl.

Benadryl is not a dangerous drug, but can make you drowsy, so if you can, ask the doctor not to give it to you. It is not easy to tell a doctor what to do, especially during a severe migraine attack. But if doctor is agreeable, ask for intravenous magnesium followed by either sumatriptan or ketorolac injection as well as metoclopramide for nausea.

Video of Botox injections for chronic migraine with TMJ

By: Dr. Mauskop

01-05-2015

Botox, injections, Migraine, TMJ

The FDA-approved protocol for Botox injections for chronic migraines calls for 31 injections with 155 units of Botox. This is the protocol we teach young doctors and new injectors.

However, just like with any other medication, doctors are allowed to go “off label”, meaning that we can inject Botox for headache types and pain conditions other than chronic migraine (in which case insurance will usually not pay) and we can also adjust the number of injection sites and the total dose of Botox when treating patients with chronic migraines. I have a fair number of patients who need up to 200 units and on a very rare occasion even 300. The maximum dose allowed during a single treatment is 400 units, which is usually needed when injecting large muscles in arms and legs, like in cerebral palsy or spasticity due to strokes.

This YouTube video shows injections for chronic migraines with additional injections into the masseter muscles (at the corner of the jaw) to treat TMJ syndrome, which is also called temporomandibular disorder. Injections of the temporalis muscles in the temples, which are also involved in chewing and which are always injected for chronic migraines, also helps relieve TMJ syndrome.

Opiates (narcotics) increase ER stay in patients with headaches

By: Dr. Mauskop

25-03-2015

Headaches, injections, Migraine

Narcotics are not only ineffective for the treatment of headaches, but they can also make headaches worse and transform an episodic migraine into chronic. A study mentioned in a previous post showed that more than half of migraine sufferers who went to an ER were given a narcotic.

A new study recently published in the journal of the International Headache Society, Cephalalgia showed that if patients presenting with a headache to an ER are treated with an injection of opiates (narcotics) they will stay in the hospital longer than if no narcotics are given. This treatment also leads to an increased risk of return visits to the emergency department within seven days.

The study was conducted by two neurologists, Dr. McCarthy at Puget Sound VA Healthcare System in Seattle and Dr. Cowan at Stanford University in California. They examined charts of 574 people and discovered that 23% received a narcotic when they were seen at an emergency department. Only 53% were given an injection of a drug recommended by a published consensus of headache experts. These include sumatriptan (Imitrex, the only injectable triptan), prochlorperazine (Compazine), metoclopramide (Reglan), chlorpromazine (Thorazine), ketorolac (Toradol), aspirin, acetaminophen, and dihydroergotamine. The remaining 24% were given an injection of another non-narcotic drug.

Patients who were given opiates were 4 times more likely to have a long stay, compared with patients given first-line recommended medications. 69 participants had at least one readmission for headache, of whom 20 returned to the emergency department within seven days. Interestingly, patients who had a CAT or an MRI scan of the brain had a significantly higher rate of early return visits, compared with those who did not have neuroimaging. Approximately 8% of people given opiates had early return visits, compared with 3% of patients given first-line recommended drugs.

Dr. McCarthy was quoted saying that “Opiates have shown less headache pain reduction, higher rates of headache recurrence, and increased sedation, compared with first-line recommended specific headache medications”. He added that regardless of whether the acute headache was diagnosed as a migraine or a tension-type headache, it is likely to respond to most non-narcotic injectable treatments.

An editorial accompanying this article concluded that “The most important intervention emergency physicians can deliver for their headache patients is to connect them with outpatient physicians savvy about headache management, who will then provide these headache patients with appropriate acute therapeutics, initiate preventive therapy, and counsel their patients against receiving opioids in the emergency department”.