Savella, although not used to treat depression, acts like an antidepressant. It is one of two antidepressant medications approved by the U.S. Food and Drug Administration to treat fibromyalgia. Savella, a serotonin-noradrenalin reuptake inhibitor (SNRI), increases the levels of the neutrotransmitters noradrenaline and serotonin in the brain and spinal cord, but the exact mechanisms by which Savella eases fibromyalgia symptoms are still unknown.
Studies have demonstrated that pain regulation is impaired in the central nervous system of fibromyalgia patients.
Using functional magnetic resonance imaging (fMRI), patients showed higher pain intensities in response to pressure and associated increases in brain activity in pain-related brain areas compared to healthy individuals (controls).
Other studies reported reduced activation of the brain’s pain inhibitory system when stimulated by pressure.
The scientists conducted a 13-week neuroimaging study (EudraCT # 2004-004249-16) to evaluate the effects of Savella at 200 mg/day on pressure pain sensitivity in 92 women with fibromyalgia. They also measured the medication’s effect on brain processing of pressure-evoked pain and assessed the treatment’s tolerability and safety.
The double-blind, placebo-controlled clinical trial included patients ages 18-55 who had a baseline mean pain intensity score of at least 40 on a visual analog scale, where 0 means no pain and 100 is the strongest possible pain.
Results revealed that treatment with Savella induced a trend toward lower pain sensitivity compared to placebo. This difference was greater at higher pain intensities. The authors wrote that the limited statistical effects may have been due to the relatively small number of patients in the study.
Patients taking Savella showed increased pain-evoked brain activity on fMRI, compared to an analysis before treatment. This was observed specifically in the nucleus caudatus, anterior insula, and amygdala, which are all brain areas regulating pain inhibition.
When compared to patients taking a placebo, those receiving Savella revealed greater pain-induced activity in the precuneus/posterior cingulate cortex after treatment, a region previously connected to fibromyalgia and a key part of the default mode network, a system of brain regions with interconnected activity.
Safety results showed that nausea was the most common treatment-related adverse event, and was reported by 71.7% of patients taking Savella and 43.5% of those on placebo. Patients receiving Savella were more likely to stop treatment due to side effects.
“The current results provide preliminary information about the mechanism of action for treatment with milnacipran (Savella) in [fibromyalgia],” the scientists wrote.
“This is the first assessment of SNRI treatment mechanisms in [fibromyalgia] and therefore provides insights for future mechanistic studies and directions for the development of novel treatment strategies,” they added.