Milnacipran for Treatment of Fibromyalgia

SNRI Antidepressant Savella Becomes Third FDA Approved Drug for FM

Jan 17, 2009

After several studies vouching for its efficacy, the antidepressant milnacipran (Savella) received FDA approval for treatment of fibromyalgia in January 2009.

Milnacipran has been used in the treatment of major depression in Europe since 1998 (under the brand name Ixel), but has not been approved in the U.S. until now. It is thought to be one of the antidepressants with the fewest side effects. In Europe it is also very inexpensive.

Mode of Action

Milnacipran belongs to the class of serotonin and noradrenaline inhibitors reuptake inhibitor (SNRI) antidepressants. Most antidepressants used today like fluoxetine (Prozac) and paroxetine (Paxil) are selective serotonin reuptake inhibitors (SSRI), but SNRI drugs also block the reuptake of noradrenaline, increasing the brain levels of this neurotransmitter.

Besides milnacipran the SNRI antidepressants also include venlafaxine (Effexor), its newer version desvenlafaxine (Pristiq) and duloxetine (Cymbalta), though Effexor has little effect on noradrenaline in low doses, making it more of an SSRI. Cymbalta was already approved as a fibromyalgia treatment in 2007. There are also drugs that only block the reuptake of noradrenaline, called NRIs.

All of these drugs can be helpful in fibromyalgia, but those that increase brain levels of both serotonin and noradrenaline (the SNRIs) are thought to be more efficacious in the treatment of fibromyalgia and other chronic pain conditions than those only affecting either one.

The SNRI drugs are somewhat similar to the old tricyclic antidepressants like amitriptyline (Elavil), which have been a mainstay of fibromyalgia treatment since the 1980s. The tricyclics, however, are quite prone to causing bothersome side effects, and because their patents have expired long ago, their manufacturers haven't tried to get them FDA approved for fibromyalgia.

Milnacipran in Fibromyalgia

The FDA requires clear demonstration of efficacy for a particular indication (condition) before approving a medication. There have been several studies showing that milnacipran is helpful for fibromyalgia, the earliest published in 2004 and the newest in late 2008.

Milnacipran does not help everyone with fibromyalgia, but a significant proportion of patients do benefit. In the 2004 study 75% of patients taking milnacipran reported improvement, compared with just 38% in the participants assigned to placebo. One does not have to be depressed to benefit from SNRI antidepressants.

Milnacipran can help a number of symptoms, such as pain, fatigue, mood, sleep, cognitive problems and urinary frequency. Effects are often noticeable in a week, but it can take several weeks before the full benefits are apparent.

Side Effects

Milnacipran is thought to have a good tolerability and may be better in this regard than duloxetine. In the fibromyalgia studies the most common side effects were nausea, headache and constipation.

Other potential adverse effects include dizziness, sweating, palpitations, dry mouth, insomnia, itching, anxiety, hot flashes and painful urination. Unlike the SSRI antidepressants, milnacipran does not usually cause sexual dysfunction or weight gain. Both high and low blood pressure are possible side effects.

Milnacipran can be combined with most other medications, but it should never be used together with St. John's wort, MAO inhibitors or the triptan class of migraine drugs, such as sumatriptan (Imitrex). It can trigger mania in bipolar disorder.

References

Vitton O, Gendreau M, Gendreau J, et al. A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Hum Psychopharmacol. 2004 Oct;19 Suppl 1:S27-35.

Gendreau RM, Thorn MD, Gendreau JF, et al. Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol. 2005 Oct;32(10):1975-85.