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Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial



Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM).


To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications.


In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18–65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. (; IRCT2016030626935N1).


Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change − 2.32, 95% CI, −4.46 to − 0.18; p = 0.034; Cohen’s d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm.


This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.

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  1. Schmidt-Wilcke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011;7(9):518–27.

    Article  PubMed  Google Scholar 

  2. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17(8):356.

    Article  PubMed  Google Scholar 

  3. Yunus MB, Inanici F, Aldag JC, Mangold RF. Fibromyalgia in men: comparison of clinical features with women. J Rheumatol. 2000;27(2):485–90.

    CAS  PubMed  Google Scholar 

  4. Häuser W, Henningsen P. Fibromyalgia syndrome: a somatoform disorder? Eur J Pain. 2014;18(8):1052–9.

    Article  PubMed  Google Scholar 

  5. Pae C-U, Luyten P, Marks DM, Han C, Park S-H, Patkar AA, et al. The relationship between fibromyalgia and major depressive disorder: a comprehensive review. Curr Med Res Opin. 2008;24(8):2359–71.

    Article  CAS  PubMed  Google Scholar 

  6. Gracely RH, Ceko M, Bushnell MC. Fibromyalgia and depression. Pain Res Treat. 2012;2012.

  7. Meeus M, Nijs J, Hermans L, Goubert D, Calders P. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013;17(9):1081–9.

    Article  CAS  PubMed  Google Scholar 

  8. Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro Endocrinol Lett. 2010;31(2).

  9. Becker S, Schweinhardt P. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res Treat. 2012;2012:741746.

    PubMed  Google Scholar 

  10. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338:114–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291–338.

    Article  CAS  Google Scholar 

  12. Thiagarajah AS, Guymer EK, Leech M, Littlejohn GO. The relationship between fibromyalgia, stress and depression. Int J Clin Rheumatol. 2014;9(4):371–84.

    Article  CAS  Google Scholar 

  13. Chinn S, Caldwell W, Gritsenko K. Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep. 2016;20(4):25.

    Article  PubMed  Google Scholar 

  14. Shakiba M, Moazen-Zadeh E, Noorbala AA, Jafarinia M, Divsalar P, Kashani L, et al. Saffron (Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: a randomized double-blind clinical trial. Avicenna J Phytomed. 2018;8(6):513–23.

    PubMed  PubMed Central  Google Scholar 

  15. Kia S, Choy E. Update on treatment guideline in fibromyalgia syndrome with focus on pharmacology. Biomedicines. 2017;5(2):E20.

    Article  CAS  PubMed  Google Scholar 

  16. Lee YH, Song GG. Comparative efficacy and tolerability of duloxetine, pregabalin, and milnacipran for the treatment of fibromyalgia: a Bayesian network meta-analysis of randomized controlled trials. Rheumatol Int. 2016;36(5):663–72.

    Article  CAS  PubMed  Google Scholar 

  17. Häuser W, Petzke F, Sommer C. Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. J Pain. 2010;11(6):505–21.

    Article  CAS  PubMed  Google Scholar 

  18. Gilron I, Chaparro LE, Tu D, Holden RR, Milev R, Towheed T, et al. Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial. Pain. 2016;157(7):1532–40.

    Article  CAS  PubMed  Google Scholar 

  19. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62(5):600–10.

    Article  Google Scholar 

  20. Beck AT, Steer RA, Brown GK. Manual for the Beck depression inventory-II. San Antonio: The Psychological Corporation; 1996.

    Google Scholar 

  21. Bennett RM, Friend R, Jones KD, Ward R, Han BK, Ross RL. The revised fibromyalgia impact questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther. 2009;11(4):R120.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ware JE Jr, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220–33.

    Article  PubMed  Google Scholar 

  23. Ware JE, Keller SD, Kosinski M. Sf-12: how to score the Sf-12 Physcial and mental health summary scales. Lincoln: QualityMetric Incorporated; 1998.

    Google Scholar 

  24. Bidari A, Hassanzadeh M, Parsa BG, Kianmehr N, Kabir A, Pirhadi S, et al. Validation of the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia in an Iranian population. Rheumatol Int. 2013;33(12):2999–3007.

    Article  PubMed  Google Scholar 

  25. Ghassemzadeh H, Mojtabai R, Karamghadiri N, Ebrahimkhani N. Psychometric properties of a Persian-language version of the Beck depression inventory-second edition: BDI-II-PERSIAN. Depress Anxiety. 2005;21(4):185–92.

    Article  PubMed  Google Scholar 

  26. Parsa BG, Maafi AA, Haghdoost A, Arabi Y, Khojamli M, Chatrnour G, et al. The validity and reliability of the Persian version of the revised fibromyalgia impact questionnaire. Rheumatol Int. 2014;34(2):175–80.

    Article  Google Scholar 

  27. Montazeri A, Vahdaninia M, Mousavi SJ, Omidvari S. The Iranian version of 12-item short form health survey (SF-12): factor structure, internal consistency and construct validity. BMC Public Health. 2009;9(1):341.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nasser K, Kivitz AJ, Maricic MJ, Silver DS, Silverman SL. Twice daily versus once nightly dosing of Pregabalin for fibromyalgia: a double-blind randomized clinical trial of efficacy and safety. Arthritis Care Res. 2014;66(2):293–300.

    Article  CAS  Google Scholar 

  29. Ellis JJ, Sadosky AB, Ten Eyck LL, Cappelleri JC, Brown CR, Suehs BT, et al. Impact of potential pregabalin or duloxetine drug–drug interactions on health care costs and utilization among Medicare members with fibromyalgia. Clinicoecon Outcomes Res. 2014;6:389–699.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Johnston SS, Udall M, Cappelleri JC, Johnson BH, Shrady G, Chu B-C, et al. Potential drug–drug and drug–condition interactions among fibromyalgia patients initiating Pregabalin or duloxetine: prevalence and health care expenditure impact. Pain Med. 2014;15(8):1282–93.

    Article  PubMed  Google Scholar 

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We would like to offer our special thanks to Dr. Nahid Kianmehr from Iran University of Medical Sciences for helping the authors with patient recruitment procedures, and Ms. Kimia Ziafat from University of British Columbia for language editing of the manuscript.


This study was supported by Iran University of Medical Sciences (Grant No. 2470). The academic institution had no role in design, conduct, data collection, analysis, data interpretation, manuscript preparation, review, or decision to submit this paper for publication.

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Correspondence to Banafsheh Ghavidel-Parsa.

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The authors of this manuscript declare that they have no competing interests.

Ethical approval

All the procedures performed were approved by the ethics committee of Iran University of Medical Sciences (code: 25371–109,861) in accordance with the World Medical Association’s code of ethics (Declaration of Helsinki, revised in Brazil 2013).

Informed consent

Written informed consent was obtained from all patients and if necessary their caregivers. It was clearly explained for the participants that their relationship with the healthcare provider would not be affected should they chose to withdraw from the study at any time.

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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Bidari, A., Moazen-Zadeh, E., Ghavidel-Parsa, B. et al. Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial. DARU J Pharm Sci 27, 149–158 (2019).

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  • Clinical trial
  • Fibromyalgia
  • Duloxetine
  • Pregabalin