What is the drug of choice for long-term treatment of fibromyalgia?

• A. Amitriptyline
• B. Venlafaxine
• C. Duloxetine
• D. Pregabalin

Answer: (D)

Fibromyalgia management centers on reducing widespread pain and improving function by targeting abnormal pain processing in the central nervous system. Pregabalin, a gabapentinoid, works by binding to the alpha-2-delta subunit of presynaptic voltage-gated calcium channels, which lowers the release of excitatory neurotransmitters. This dampens neuronal hyperexcitability and central sensitization that underlie fibromyalgia symptoms, leading to meaningful improvements in pain, sleep disturbance, and daytime functioning.

Long-term data show that pregabalin provides sustained benefit with a tolerability profile that makes it practical for chronic use, including steady pain relief and better sleep over extended periods. These advantages help patients maintain daily activities and quality of life, which is why pregabalin is considered the best option among the choices for ongoing treatment.

Amitriptyline can aid sleep and pain but carries anticholinergic and sedative side effects that limit long-term use for many patients. Venlafaxine offers some pain relief but has less consistent long-term fibromyalgia data and tolerability concerns in practice. Duloxetine is also effective and approved for fibromyalgia, but pregabalin’s combination of direct impact on central sensitization, sleep improvement, and robust long-term trial evidence often makes it the preferred choice for chronic management.