To the Editor The thorough, systematic review of therapies for fibromyalgia written by Mascarenhas et al1 concludes that antidepressants and central nervous system depressants are effective treatments for this condition, but the effect sizes are small and fail to reach the threshold for clinical importance. While their findings are congruent with clinical trials, their discussion assumes that most patients with fibromyalgia are treated with a single modality at a time (pharmacologic or otherwise); however, the current standard of care for fibromyalgia and other chronic pain conditions is to use a stepped care model where multiple therapies are layered atop one another sequentially to achieve meaningful improvements in multiple symptom domains over time. There is mounting evidence for this approach; for example, there are higher overall response rates in patients with fibromyalgia who are treated with a serotonin-norepinephrine reuptake inhibitor and an α2δ-subunit calcium channel ligand together, than with either alone.2 Similarly, there are greater reductions in pain for patients receiving duloxetine plus pregabalin than for those receiving either alone.3 The increased effectiveness of layering therapies is not surprising given that pain testing and functional neuroimaging have demonstrated that that there are various neurotransmitter and receptor abnormalities present in centralized or nociplastic pain conditions like fibromyalgia, and it is unlikely that any single therapy will work well in most patients.4 Thus, clinicians should not necessarily discount a treatment because it alone fails to make an analgesic impact that reaches the threshold for what is clinically meaningful. Moreover, we believe that it is important to place expectations for fibromyalgia treatments into the perspective of treatments for other types of chronic pain. The small effect sizes of these classes of drugs in treatment of fibromyalgia are similar to those of analgesics for any chronic pain condition, including paracetamol and nonsteroidal anti-inflammatory drugs for osteoarthritis.5
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Silveira MJ, Boehnke KF, Clauw D. Treatment of Fibromyalgia in the 21st Century. JAMA Intern Med. 2021;181(7):1011. doi:10.1001/jamainternmed.2020.9276
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