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Mind and Muscle: A Retrospective Study on the Management of Psychiatric Comorbidities in Patients With Fibromyalgia Treated With Pregabalin Versus Milnacipran
Journal article   Open access   Peer reviewed

Mind and Muscle: A Retrospective Study on the Management of Psychiatric Comorbidities in Patients With Fibromyalgia Treated With Pregabalin Versus Milnacipran

Angelica Arshoun, Andrew S Murdock and Eduardo D Espiridion
Curēus (Palo Alto, CA), v 18(2), e103154
07 Feb 2026
DOI: https://doi.org/10.7759/cureus.103154
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https://doi.org/10.7759/cureus.103154View
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Abstract

Background: Fibromyalgia syndrome is a debilitating chronic disease with symptoms of pain and fatigue that profoundly impact patients’ quality of life. This disability can lead to the development of psychiatric comorbidities, causing a compounding decline in overall well-being. Pregabalin and milnacipran are options for patients seeking symptomatic relief, but we hypothesized that psychiatric outcomes differ between patients with fibromyalgia treated with milnacipran versus pregabalin. Methods: TriNetX, a de-identified healthcare organization (HCO) network, collected and analyzed the study data. Patients with fibromyalgia receiving either milnacipran or pregabalin without opioid analgesics were included in this study and separated based on their use of milnacipran or pregabalin. Risk difference, risk ratios, Kaplan-Meier analysis with log-rank tests (LRTs), hazard ratios, and proportionality were analyzed for differences among several conditions: somnolence, opioid use disorder (OUD), depressive episodes (DEs), and anxiety disorder (AD) between patients on milnacipran versus pregabalin. Results: In total, 119,406 patients met the eligibility criteria, and propensity score matching resulted in 6,726 patients in each cohort. Milnacipran decreased the risk of somnolence and OUD (somnolence: 0.942%, 95% confidence interval (CI): 0.0445-1.44%, p<0.001; OUD: 0.779%, 95% CI: 0.061-1.5%, p<0.0333) (DEs: 2.1%, 95% CI: 0.3-3.89%, p=0.217; AD: 1.18%, 95% CI: -0.623-2.99%, p=0.119). Kaplan-Meier analysis demonstrated the benefit of milnacipran in the management of somnolence. There is no difference in the management of anxiety. There was a trending improvement in OUD and DE with milnacipran, but it did not show clear superiority (LRT somnolence, p<0.001; OUD, p=0.0584; DE, p=0.0504; anxiety, p=0.441). Conclusion: Overall, differences observed between groups may not be clinically significant. This information may help clinicians and patients employ well-informed, shared decision-making.

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