Milnacipran Did Not Help Pain Modulation in Fibromyalgia Clinical Trial, Results Showed

Milnacipran Did Not Help Pain Modulation in Fibromyalgia Clinical Trial, Results Showed

Milnacipran (brand name Savella), an antidepressant that is widely prescribed for pain in fibromyalgia patients, did not significantly reduce pain compared to placebo after one month of treatment, French researchers found.

Their study, “Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study,” was published in the journal Drug Design, Development and Therapy.

Patients with fibromyalgia experience chronic pain, especially in the joints and muscles associated with fatigue.

Pain is a subjective experience. Fibromyalgia patients are known to have “altered central modulation” of pain, which refers to refers to processes in our central nervous system that can ease or block the pain experience.

The degree to which a patient can modulate the pain experience can be tested using an experimental technique called conditioned pain modulation (CPM).

Studies have also shown that fibromyalgia patients exhibit dysregulation of neurotransmitters (important signaling molecules that activate the nervous system). Because antidepressants can increase the levels of neurotransmitters in the brain, they may be used in the treatment of fibromyalgia.

Specifically, an antidepressant called milnacipran helps regulate levels of neurotransmitters known as monoamines (dopamine, noradrenaline, and serotonin), which are known to be involved in modulating pain.

As a result, milnacipran is often prescribed to fibromyalgia patients. But there are few studies that directly show that milnacipran is associated with improving the central modulation of pain.

Researchers in France conducted a study aimed at determining whether milnacipran can improve CPM results by reactivating the effectiveness of pain modulation in fibromyalgia patients.

They conducted a randomized, controlled trial (NCT01747044) in women with fibromyalgia to evaluate the effectiveness of conditioned pain modulation with 100 mg of milnacipran compared to placebo (lactose capsules) after one month of treatment.

The primary endpoint of the study was a change in CPM after a 30-second painful stimulus (CPM30). Fifty-four women with fibromyalgia were enrolled in the study and randomized to either the medication or the placebo, with 24 patients in each group.

As expected, at baseline, CPM30 was found to be dysfunctional with high global pain levels.

But unexpectedly, after treatment, researchers found no significant differences in CPM30 between the treated patients and the placebo, suggesting there were no significant differences in central pain modulation.

Interestingly, 18.8% of patients experienced reactivation of CPM after milnacipran compared to 6.3% after placebo treatment. This would indicate that more patients in the treated group become “inhibitory” and felt less pain than those in the placebo group.

However, these results were not statistically significant.

The secondary endpoints, including global pain, mechanical and thermal thresholds, allodynia (pain from stimuli that doesn’t normally cause pain), cognition, and tolerance were also not significantly different between the two groups.

Regarding safety, researchers found that 96% of fibromyalgia patients developed adverse events in the treated group, including gastrointestinal disorders, general disorders, and nervous system disorders, some of which led to withdrawal from the study (five patients in the treated group, one in the placebo group).

“Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnacipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients,” the researchers wrote.

“It is important to stress the poor efficacy of milnacipran in the current trial,” they added, because milnacipran is recommended for fibromyalgia in several countries.