First-line treatment for fibromyalgia is which pharmacologic class?

• A. Serotonin-norepinephrine reuptake inhibitors (SNRI)
• B. Selective serotonin reuptake inhibitors (SSRI)
• C. Tricyclic antidepressants (TCA)
• D. Benzodiazepines

Answer: (A)

Fibromyalgia pain is driven in part by amplified pain signaling in the central nervous system, so treatments that boost the body’s descending pain inhibition can be particularly effective. Serotonin-norepinephrine reuptake inhibitors do just that by increasing both serotonin and norepinephrine in the synapse, which strengthens the brain’s ability to dampen pain signals. This mechanism helps reduce widespread pain, improve sleep, and lift fatigue and mood, and there is strong clinical evidence supporting their use as a first-line pharmacologic option. Duloxetine and milnacipran are the usual examples.

SSRIs, while they raise serotonin, don’t enhance norepinephrine to the same extent and have less robust data for fibromyalgia pain relief. TCAs can help some patients but carry more anticholinergic and cardiac risks and can be less tolerable. Benzodiazepines don’t address the underlying pain mechanism and carry risks of dependence and sedation, making them unsuitable as first-line therapy for fibromyalgia.