Milnacipran (Savella) is a drug that is approved by the FDA for the treatment of fibromyalgia. Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas.

Milnacipran belongs to the category of selective serotonin and norepinephrine reuptake inhibitors (SNRIs), which are used to treat anxiety, depression, and pain. There are four other SNRIs that are approved for the treatment of anxiety and depression, and in case of duloxetine (Cymbalta) also for fibromyalgia, peripheral nerve damage due to diabetes and musculoskeletal pain.

The manufacturer of milnacipran decided not to seek approval for the treatment of depression to avoid the stigma of being an antidepressant drug. Many patients feel that if they are prescribed an antidepressant, their pain is not perceived as real physical pain, but rather purely psychological.

Milnacipran was tested for the preventive treatment of migraines only in one unblinded observational study. Not surprisingly, it was effective. We often use duloxetine and venlafaxine (Effexor) for the treatment of migraines. Fibromyalgia, back pain, and other pains are comorbid with migraines, meaning that if you have one condition, you are more likely to have the other as well. Such patients are ideal candidates for SNRIs, although tricyclic antidepressants such as amitriptyline also work well for any pain and migraines.

Just like with other SNRIs, the most common side effects include nausea, headache, constipation, dizziness, insomnia, hot flushes, hyperhidrosis (excessive sweating), vomiting, palpitations, increased heart rate, dry mouth, and hypertension. Another common problem with these drugs is that many patients develop very unpleasant withdrawal symptoms if the drug is stopped abruptly.

Theoretically, antidepressants when used with triptans, such as sumatriptan can cause serotonin syndrome, but it is extremely rare and millions of people take both without any problems.

When sumatriptan (Imitrex) was introduced in 1992 it was truly a breakthrough drug – the first drug specifically developed for the acute treatment of migraines. Sumatriptan and six other triptans have alleviated suffering of millions of people. Sumatriptan is considered to be the gold standard therapy for an acute migraine. Unfortunately, 27 years later many millions of migraine sufferers have not had a chance to try these drugs.

A study by R. Lipton and his colleagues presented earlier this year surveyed 15,133 migraine sufferers. Only 37% had ever used a triptan and only 16% were using them at the time of the survey. Most patients used tablets, but 11% also tried either a nasal spray or an injection. Lack of efficacy (in 38%) and side effects (in 22%) were the most common reason for stopping the drug and the most common side effects were dizziness, nausea, and fatigue.

My guess is that lack of efficacy is often due to the suboptimal dose of a triptan that is often prescribed. I see many patients who tell me that they’ve tried sumatriptan and it did not work, but many of them took 25 or 50 mg, while an effective dose for most patients is 100 mg. Most other triptans are also available in two different strengths and the lower, less effective dose is often prescribed.

Another common problem is that patients who fail one triptan due to side effects or lack of efficacy are not prescribed a different triptan. Many of my patients find that one triptan is more effective than another or if one triptan causes side effects, a different one may not. Also, if a tablet does not work, an injection or a nasal spray might, especially in patients with a quick buildup of pain or when nausea is present.

A big reason for the underutilization of triptans is misdiagnosis of headaches. Almost half of migraine sufferers are told that they have sinus or tension headaches, which means they are missing out on receiving effective treatment.

Safety of triptans is a concern of many physicians and patients. The package insert warns about strokes and heart attacks and it is true that if you have untreated hypertension, coronary artery disease or many risk factors for coronary artery disease it is better to avoid triptans. However, triptans have been available without a prescription for over 10 years in most European countries.

A panel of leading headache specialists published a “Consensus Statement: Cardiovascular Safety Profile of Triptans in the Acute Treatment of Migraine” that states “The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low “.

Another unfounded concern of many physicians is that frequent use of triptans will make migraines more frequent and severe. There is no good scientific evidence for this concern. You can read my two previous blog posts on this topic here and here. The first of these two posts is by far the most popular on this site with over 300 comments. Many patients report how relieved they are to hear that they are not risking their lives by taking triptans often or even daily and also how frustrated they are not being able to find a doctor who would prescribe a sufficient amount of this medicine.

Sumatriptan was first released in a pack of 9 tablets, but not because it was dangerous to take more, but mostly because this was the average number of tablets people used in one month in clinical trials. Cost used to be another limiting factor and some insurers still limit triptans to 6 or 9 tablets a month. However, generic sumatriptan now can be found for as little as $12-20, so patients can bypass their insurance and buy as many additional tablets as they might need.