Which medications are FDA-approved for fibromyalgia and what is a common mechanism?

• A. Duloxetine, milnacipran, pregabalin; modulate monoaminergic pathways to reduce central pain amplification.
• B. Only duloxetine approved; acts as a direct analgesic.
• C. Milnacipran is in the NSAID class.
• D. Pregabalin acts by increasing endorphin release.

Answer: (A)

Fibromyalgia drugs work best when they dampen the brain’s amplification of pain signals. The three FDA-approved options—duloxetine, milnacipran, and pregabalin—do just that, though by slightly different routes. Duloxetine and milnacipran are serotonin-norepinephrine reuptake inhibitors, so they raise levels of these monoamines in the synapse and enhance descending inhibitory pathways that blunt pain signals from reaching conscious perception. Pregabalin, a gabapentinoid, binds to the α2δ subunit of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters and neuronal hyperexcitability. Taken together, these medications target central sensitization rather than just peripheral pain, which is why they’re approved for fibromyalgia.

The other options misstate either the approval status or the mechanism: one asserts only duloxetine is approved and acts as a direct analgesic, another wrongly classes milnacipran as an NSAID, and another claims pregabalin increases endorphin release.