Botox relieved severe pain of SUNCT, a rare and very painful condition, according to a report recently published in journal Cephalalgia. SUNCT stands for short-lasting, neuralgiform headache attacks with conjuctival injection and tearing. The pain of SUNCT is very sudden and brief, lasting 5 to 240 seconds and occurring 20-30 or more times a day. The pain usually occurs around the eye and is accompanied by tearing and redness of the eye. It can be a very debilitating condition because it is difficult to treat. Medications, such as lamotrigine (Lamictal), gabapentin (Neurontin), carbamazepine (Tegretol), and other have been reported to help. The report in Cephalalgia by a Spanish neurologist describes a patient with SUNCT who did not respond to a variety of medication and nerve destruction (thermocoagulation of the trigeminal ganglion), but had an excellent response to Botox injections given every three months. He has received 10 Botox injections over a period of 2 and 1/2 years with sustained relief. He was still having 6-8 attacks per week, but before Botox he was having 20-30 a day. His functioning has also significantly improved. Botox is approved by the FDA only for chronic migraines, although it also seems to work for cluster headaches, which cause pain similar to SUNCT, although it lasts for 1-3 hours and occurs once or twice a day. SUNCT is a very rare condition and it is very unlikely that a blinded clinical trial of Botox for SUNCT will ever be conducted, but this report suggests that Botox may be worth trying in patients with SUNCT.

Zecuity was just approved by the FDA for the treatment of acute migraines. Zecuity is a skin patch containing sumatriptan. Delivering sumatriptan through the skin is an appealing option for patients who have severe nausea or vomiting and have difficulty swallowing tablets. NuPath is a company that has been working on such a delivery system for several years and I mentioned their research in one of the posts on this blog over three years ago. Recently, they completed another clinical trial which confirmed that the idea is valid and their product (it was first named Zelrix, but now is to be called Zecuity) is effective in treating migraine attacks. The patch containing sumatriptan delivers medicine through the skin with the help of an electrical current derived from a miniature battery embedded within the patch. The patch is used once and then is discarded. The results of this trial were published in the journal Headache. This study involved 469 patients half of whom treated their migraine with an active patch and the other half with an inactive (placebo) patch. A significantly higher proportion of patients given sumatriptan were completely pain-free compared to those who were given placebo – 18% vs 9%. Pain relief after two hours was observed in 53% patients receiving sumatriptan compared to 29% of those receiving placebo and this difference persisted. Side effects were mostly local due to the patch – 23% had pain at the site of patch, 20% had either burning of tingling, and 7% had other types of skin reaction, but only 2% had a reaction severe enough that they took the patch off. Zecuity (transdermal sumatriptan) appears to offer a good option for migraine sufferers who cannot take oral medications and do not want to inject themselves with sumatriptan.

Occipital nerve stimulation (ONS) has been reported to relieve refractory (difficult to treat) migraine headaches. Results of a clinical trial of ONS for patients with refractory migraine was just published in the journal Cephalalgia. This study was sponsored by St. Jude Medical, company that manufactures occipital nerve stimulators. This was a large (157 patients) and very scientific (randomized, controlled) study.?Patients were considered refractory if they failed two prophylactic migraine medications, such as blood pressure medications, anti-epilepsy drugs, or anti-depressants. Of the 157 patients, 105 patients had real stimulation and 52 had sham stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ?50% reduction in pain scores after 12 weeks). The researchers found no significant difference in the percentage of responders in the Active compared with the Control group. The authors of the report suggest that had they used different measures of efficacy, the results would have been positive and they are calling for more studies. The most common adverse event was persistent implant site pain, which occurred in 15% of patients. The editorial by Hans-Christoph Diener, one of the leading headache experts suggested that the efficacy of this treatment appears to be very low, while side effects and costs are quite significant. The cost of the stimulator and of the surgery to implant it ranges from $20,000 to $40,000. Another problem with the study is that it did not require that patients fail Botox injections before they were enrolled in this trial. Botox is known to be effective for the treatment of migraine headaches in many patients who fail prophylactic medications. Botox is not only very effective, but is also significantly cheaper and much safer.

I just saw a man with chronic cluster headaches whom I’ve been treating for the past 5 years. He had tried various treatments and still remains on verapamil which provides partial relief, but he finds excellent relief from monthly intravenous infusions of magnesium and Botox injections given every 2 to 4 months. He sometimes needs a magnesium infusion every three weeks. He occasionally takes sumatriptan (Imitrex) injections as needed for breakthrough headaches, but many of his remaining attacks are mild and are relieved by rizatriptan (Maxalt) tablets or zolmitriptan (Zomig) nasal spray. Botox is not approved by the FDA for the treatment of cluster headaches, only for chronic migraines. However, there are several case reports of successful use of Botox in patients similar to mine. I’ve treated several other cluster headache patients with Botox with good results, but this is the only one who has been receiving Botox for three years (he has had 15 treatments to date). As far as the use of intravenous magnesium, we’ve published an article showing that 40% of patients with cluster headaches are deficient in magnesium and respond to intravenous infusions.

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A small number of my patients take triptan medications daily. Many doctors, including neurologists and headache specialists think that taking these drugs daily makes headaches worse, resulting in rebound, or medication overuse headaches (MOH). However, there is no evidence to support this view. Sumatriptan (Imitrex, Treximet), rizatriptan (Maxalt), zolmitriptan (Zomig), naratriptan (Amerge), eletriptan (Relpax), almotriptan (Axert), and frovatriptan (Frova) have revolutionized the treatment of migraines. I started my career in 1986, five years before the introduction of sumatriptan when treatment options were limited to ergots with and without caffeine (Cafergot), barbiturates with caffeine and acetaminophen (Fioricet), and narcotic or opioid drugs (codeine, Vicodin, Percocet). These drugs were not only ineffective for many migraine sufferers, but they also made headaches worse. Dr. Richard Lipton and his colleagues followed over 8,000 patients with migraine headaches for one year. Results of their study showed that taking barbiturates (Fioricet, Fiorinal) and narcotic pain killers increased the risk of migraines become more frequent and even daily and resulting in chronic migraines. We know from many other studies that withdrawal from caffeine and narcotics can result in headaches. However, taking triptans and non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin (Migralex), naproxen (Aleve), ibuprofen (Advil, Motrin) does not lead to worsening of headaches. Only those patients who were taking NSAIDs very frequently to begin with were more likely to develop even more frequent headaches at the end of the year. Aspirin, in fact, was found to have preventive properties – if you were taking aspirin for your migraines at the beginning of the year you were less likely to have worsening of your headaches by the end of the year.
There are also studies showing that NSAIDs taken daily can be effective for the prophylactic (preventive) treatment of migraine headaches. Unfortunately, no studies have been done to show that taking triptans daily can also prevent headaches.
Over the years, I have treated dozens patients with daily triptans. Prescribing sumatriptan or another triptan for daily use was never my original intent. However, most of these patients failed multiple preventive medications, Botox injections, various supplements, biofeedback and acupuncture. Because of the widespread belief that triptans cause rebound headaches most of them tried to stop taking these drugs. After a week or even several weeks, their headaches did not improve, as should be the case with rebound or MOH. In fact, most of them became unable to function and I would resume prescribing 30 and up to 60 tablets of a triptan each month. Sometimes I would prescribe 6 of one, 9 of another, and 18 tablets of the third triptan, depending on what the insurance company would allow. For some patients all triptans work equally well, for some several do, and for others only one out of seven would provide good relief without causing side effects.
The cost of these drugs, even after sumatriptan going generic, has been very high and is now the main obstacle for most patients. The original main concern we had early after the introduction of triptans was the potential serious side effects. But now, 20 years of experience strongly suggests that taking triptans daily does not cause any serious long-term side effects. I do not suggest that they cannot or do not cause serious side effects – they can and do and are contraindicated in patients with coronary artery disease and strokes, but in healthy people they are very safe. For the past several years, triptans have been available in Europe without a prescription.
In conclusion, daily triptans can be a highly effective and safe treatment for a small group of patients with chronic migraine headaches. They should not be prescribed for the prevention of migraines or for daily abortive use, unless other options (excluding barbiturate, caffeine, or narcotics) have been tried.

Botox, or onabotulinumtoxinA was recently approved by the FDA for treatment of chronic migraine based on the results of two large studies. Botox is the only prophylactic therapy specifically approved for chronic migraine. Many patients and doctors alike wonder about the mechanism of action of Botox. We originally thought that Botox works by relaxing tight muscles around the scalp. Studies have shown that during a migraine attack, the muscles in the forehead, temples and the back of the head are in fact contracted. It is also typical for a person with a migraine to rub their temples or the neck, which provides some temporary relief. However, I have seen some patients who would report that injecting muscles around the head eliminated pain in the injected areas, but that they still had pain on the top of the head. There are no muscles on the top of the head and we usually do not inject Botox there, but in those patients who do have residual pain on the top, injecting Botox stops the pain. Recent research has shown that Botox in fact also exerts a direct analgesic (pain-relieving) effect. This is supported by my and other doctors’ observation that Botox also helps other types of pain, such as that of shingles or trigeminal neuralgia. These are so called anecdotal reports and cannot be relied on to make definitive conclusions – we need large trials can prove this. It appears that Botox helps by reducing pain messages sent to the brain from both muscles and peripheral sensory nerves. This explains why migraine, which is a brain disorder, can be helped by a procedure directed only at the peripheral nerves – with the reduction of the barrage of pain messages reaching the brain, the brain does not become more and more excitable, or “wound-up” and a migraine attack does not occur. Some patients tell me that after Botox treatment they sometimes feel that a migraine is about to start, but it does not.

Intravenous infusion of magnesium for the treatment of an acute migraine is receiving more attention and is mentioned in the recent issue of journal Headache. In the first of three articles Drs. Nancy Kelley and Deborah Tepper of the Cleveland Clinic describe the use of triptans (such as sumatriptan, or Imitrex), DHE (dihydroergotamine), and magnesium for the emergency treatment of migraines. In their article they included seven reports of the use of magnesium infusion, all with positive results. We published the very first article on the use of intravenous magnesium for migraines in 1995. In the same year we published our results of the use of this treatment for cluster headaches, also a first and since that time have been promoting the use of this safe and effective treatment in many articles, lectures, and symposia. We’ve found that 50% of patients with migraines and 40% of those with cluster headaches responded to magnesium infusion. Unfortunately, many patients seen in the emergency room still do not receive magnesium, but in the best case sumatriptan or ketorolac injection, in the worse, narcotic drugs. An infusion of magnesium should be always tried first. We actually discourage our patients from going to the emergency room during office hours – instead they come to our office and are given an infusion of magnesium. If it is ineffective, then we proceed with sumatriptan, ketorolac, dexamethasone, other drugs, and sometimes nerve blocks.
Oral magnesium is not suitable for the acute treatment of a severe headache because it is absorbed too slowly. However, Migralex, a drug containing magnesium and aspirin was developed to dissolve and absorb quickly, so it can deliver magnesium (along with aspirin) to the brain within 15 – 30 minutes. Another article in the same issue of Headache recommends the use of aspirin as the first line treatment for migraine and tension-type headaches, regardless of their severity. Many doctors use “stratified” approach, which means that they recommend aspirin for milder headaches and a prescription drug, such as sumatriptan, for more severe attacks. However, the authors reviewed results of studies involving thousands of patients and concluded that aspirin can be very effective for many patients with a severe headache and should be tried first. If it is ineffective, then the patient is advised to take the prescription drug.

The FDA approved Botox for the treatment of chronic migraine because of the two large double-blind and placebo controlled trials which involved close to 1,400 patients (in which we, at the NYHC also participated). These studies showed that Botox reduced the number of days with headaches and it also improved many other related aspects. A study just published in Neurology looked at the effect of Botox on the quality of life of patients that participated in these trials. It is possible to have a treatment that reduces the number and even the severity of migraines without improving patients’ quality of life because of its side effects. This is seen with some patients who take topiramate (Topamax) – their headaches may be much better but the quality of life is not because of memory impairment or fatigue, which makes them unable to function. The same is true with other medications, such as antidepressants. However, the quality of life of patients receiving Botox in these two studies was significantly better than in those receiving placebo injections. This is because their headaches improved dramatically and because Botox rarely caused any side effects. Unfortunately, many insurance companies will pay for Botox only after the patient fails to improve on 2 or 3 prophylactic medications, even though these medications are not approved by the FDA for chronic migraines.

Cluster headaches are relieved by steroid injections in the back of the head, according to a study by French doctors, published in The Lancet. 43 patients with chronic and episodic cluster headaches were recruited into this blinded study where some patients received a steroid (cortisone) injection and some received saline water. The injections were given in the back of the head under the skull, on the side of headache. Injections were repeated every 2 – 3 days for a total of 3 injections. There was a significant improvement in patients who received cortisone. This study supports the wide use of a similar procedure, an occipital nerve block to relieve cluster headaches. In this study patients were allowed to take oxygen and sumatriptan (Imitrex) as needed. They were also started on verapamil for the prevention of cluster headaches and the injections were used for short-term relief while awaiting for the effect of verapamil to kick in. In my experience, some patients, especially those with episodic cluster headaches, may have complete resolution of their headaches just from the nerve block. Sometimes a single block is sufficient, but occasionally it helps for only a few days and needs to be repeated. It is likely that the injection technique and doctor’s experience can make a difference. Another option to stop cluster headaches is to take an oral steroid medication, such as prednisone, but taking it by mouth is more likely to cause side effects. Verapamil is an effective preventive drug, but it usually needs to be taken at a high dose – starting with 240 mg and going up to 480, 720 mg, and even higher. Verapamil is a blood pressure medication and before starting it and before increasing the dose an EKG is usually taken as it is contraindicated in people with some heart problems. In addition to verapamil, topiramate (Topamax), lithium, other drugs, and even possibly Botox injections can prevent attacks.