Cost-Effectiveness of Pregabalin, Duloxetine, and Milnacipran vs Amitriptyline for Moderate to Severe Fibromyalgia.

Importance: Fibromyalgia (FM) is a chronic pain condition associated with substantial quality-of-life impairments and economic burden. Although multiple pharmacologic options are recommended in clinical guidelines, the relative cost-effectiveness of off-label amitriptyline compared with FDA-approved treatments remains poorly defined due to a scarcity of direct economic comparisons and the use of heterogenous outcome measures in the extant literature. Objective: To evaluate the cost-effectiveness of pregabalin, duloxetine, and milnacipran compared with amitriptyline in adults with moderate to severe FM. Design, Setting, and Participants: Decision analytical model using a Markov cohort state transition model to estimate lifetime costs and quality-adjusted life-years (QALYs) for each investigated pharmacologic strategy. Model inputs included treatment-specific transition probabilities, utility values, and direct and indirect costs for each health state, which were derived from published sources. The simulated cohort reflected adults (aged ≥18 years) with moderate to severe FM. Data were analyzed between September 2024 and February 2025. Exposure: Amitriptyline (25-100 mg), pregabalin (150, 300, 450, and 600 mg), duloxetine (60 and 120 mg), and milnacipran (100 and 200 mg), evaluated from US health care payer and societal perspectives. Main Outcomes and Measures: Expected lifetime cost, QALYs, incremental cost-effectiveness ratios (ICERs), and incremental net monetary benefit (iNMB) at willingness-to-pay (WTP) thresholds of $50 000, $100 000, and $150 000 per QALY. Results: The simulated cohort included predominantly women (94.4%), had a mean (SD) age of 48.4 (10.4) years, and was parameterized using demographic distributions derived from published FM populations. From the US health care payer perspective, duloxetine 120 mg was associated with increased QALYs versus amitriptyline at slightly higher cost (ICER, $1536 per QALY), while pregabalin 450 mg was dominated by duloxetine 120 mg. When societal costs were considered, duloxetine 120 mg and pregabalin 450 mg were cost saving relative to amitriptyline. Amitriptyline remained both more effective and less costly than milnacipran, lower doses of pregabalin and duloxetine, and no treatment. At a $100 000 WTP threshold, iNMB for duloxetine 120 mg was $40 375 from the health care payer perspective and $70 063 from the societal perspective; for pregabalin 450 mg, iNMB was $21 211 and $40 190 for the health care payer and societal perspectives, respectively. Conclusions and Relevance: In this decision analytical model, duloxetine 120 mg was the preferred strategy across perspectives; pregabalin 450 mg was economically favorable relative to amitriptyline only when societal costs were included. Amitriptyline provided greater net benefit than milnacipran and the lower doses of pregabalin and duloxetine. These findings may help inform the selection of value-based treatments for moderate to severe FM.