Naratriptan (Amerge, Naramig) is a triptan with a longer duration of action of 6 hours, compared to sumatriptan, rizatirptan, zolmitriptan, eletriptan, and almotriptan, which work for 2-4 hours. The seventh triptan, frovatriptan has the longest half-life of 26 hours, but its overall efficacy is not as good as than that of other triptans. These numbers of 6, 2-4 and 26 hours actually refer to drug’s half-life – the time it takes for the blood level of the drug to drop by half.

The duration of the effect is not important for most migraine sufferers because a quick-acting and highly effective drug stops the migraine process and there is no need for it to remain in the body. However, in some patients sumatriptan or another short-acting triptan may relieve symptoms for 4-6 hours and then migraine returns. Taking a second dose often works well, but not always. Those patients can benefit from taking naratriptan. Naratriptan also tends to have fewer side effects.

The longer half-life makes naratriptan better suited for “mini-prophylaxis” – taking a drug daily for several days to prevent a predictable menstrual migraine. However, sumatriptan has been also shown to work in this manner.

Just like with other triptans, naratriptan can be combined with ibuprofen or naproxen for better efficacy. Many insurers limit the number of pills they will pay for to 6 or 9, but naratriptan, along with sumatriptan and rizatriptan is one of the cheaper triptans. This allows patients to buy additional quantities, although many doctors have the mistaken belief that triptans cause medication overuse headaches and refuse to write prescriptions for more than 9 pills a month.

Naproxen (Aleve, Anaprox, Naprosyn) is a popular over-the-counter and prescription non-steroidal anti-inflammatory drug (NSAID), which is often used for the treatment of migraine headaches. A combination of naproxen with sumatriptan (Treximet) is approved by the FDA for the treatment of acute migraine attacks. Naproxen alone, while not specifically approved for the treatment of migraines, is widely considered to be an effective drug. A review of several double-blind studies confirmed this observation. It has the advantage of having longer duration of effect when compared to ibuprofen or aspirin.

Naproxen has been also studied and proven effective in a double-blind study for the prevention of migraine attacks.  In another double-blind study naproxen, 550 mg taken twice a day was also effective for the prevention of menstrual migraines. It also helped relieve premenstrual pain. Naproxen is rarely used for the long-term prevention of migraines because of the risk of stomach ulcers and stomach bleeding.

NSAIDs carry a warning about the potential negative effects on the heart, but it should be of no concern to most migraine sufferers who tend to be young women with no risk factors for heart problems and who take naproxen only intermittently.

There is a myth that NSAIDs (and triptans) can cause rebound or medication overuse headaches (MOH). There is no scientific proof that this happens and in fact, when someone suffers from MOH due to caffeine-containing drugs (Excedrin, Fioricet) or opiates, naproxen is often prescribed to help withdrawal headaches.

Haloperidol (Haldol) is a psychiatric drug prescribed  for the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, nausea and vomiting, delirium, agitation, and acute psychosis.

A cases series published in The Journal of Emergency Medicine in 1995 described six patients who presented with a severe migraine to an emergency room in Toronto and were given haloperidol intravenously. Within an hour all six were either pain-free or significantly improved and none returned to the emergency room within 48 hours.

A double blind placebo controlled study published by Finnish researchers in the journal Headache in 2006 examined the efficacy of 5 mg of haloperidol given intravenously in the treatment of severe migraines. Forty patients were enrolled in the study and 80% (16 patients out of 20) of those who received haloperidol had significant pain relief, compared with 15% (3 patients) in the placebo group. Because the majority of patients had taken regular NSAIDs analgesics and triptans without response, the authors concluded that haloperidol appears to be effective in treatment resistant migraine attacks. However, almost all patients who receive haloperidol complained of side effects, mostly sedation and unpleasant restlessness (akathisia). The side effects were mild to moderate in severity and reversible. The restlessness can be relieved by diphenhydramine (Benadryl).

Haloperidol is one of the neuroleptic drugs, a category that includes droperidol and phenothiazine drugs such as chlorpromazine mentioned in an earlier post. All these drugs have the potential to cause serious and in rare cases permanent neurological side effect of involuntary movements. This is why they are mostly used when other acute migraine therapies have failed. The neurological side effects are more common with continued daily use of haloperidol and other neuroleptics in psychiatric disorders.

Eletriptan (Relpax) is one of seven triptans approved for the treatment of an acute migraine. While all triptans are similar (but not identical) to each other in their indications, contraindications, side effects and drug interactions, some are more effective than other. Sumatriptan (Imitrex) is the oldest triptan (approved in 1992) and with many companies making generic copies, it is the cheapest. Sumatriptan, rizatriptan (Maxalt), zolmitriptan (Zomig), eletriptan, and almotriptan (Axert) are similar in their efficacy, but many patients prefer one over another. It is not clear why this may be the case because they all work on the same two very specific serotonin receptor subtypes (5HT-1b and 5HT-1d). I do have a fair number of patients who find eletriptan to be significantly better than other triptans. Generic copies of eletriptan came on the market relatively recently and their price is still relatively high – $10 a pill, compared to $1 for sumatriptan. Brand versions of triptans cost anywhere from $40 for a pill of Maxalt (rizatriptan) to $120 for each pill of Zomig (zolmitriptan). A very rare patient of mine finds that the generic copies are significantly less effective than the brand. It is even more rare for an insurance plan to pay for it.

Eletriptan is available in 20 and 40 mg tablets with the maximum FDA-approved daily dose of 80 mg. However, in some European countries eletriptan is sold in 80 mg tablets and the maximum approved daily dose is 160 mg. I see many patients who are warned by their doctors not to exceed the maximum recommended dose on any particular day and not take a triptan on more than two days a week. The first admonition is supposedly due to the immediate danger of these drugs and the second, due to the risk of medication overuse headaches. Neither prohibition is based on good scientific evidence.

The top five triptans listed above has a very short half-life, which means that they are washed out of the body within a few hours. So if a patient calls me and says that she took a tablet the night before, then another one in the morning and by early afternoon the headache returned, I do reassure her of the safety of taking a third dose. Rizatriptan is the only triptan that is approved by the FDA for up to three doses a day. Since there is nothing unique about rizatriptan, clearly there is no risk in taking other short-acting triptans three times a day as well. Also, there is no documented risk of taking double of the maximum recommended dose of any triptan. This is rare, but some of my patients do very well with 80 mg of eletriptan or 200 mg of sumatriptan, while lower doses are ineffective. In many European countries eletriptan and other triptans are sold without a prescription, indicating their excellent long-term safety profile. This is not to say that triptans have no potential to cause serious side effects, but for a young healthy woman who is a typical migraine sufferer, these drugs are extremely safe.