Efficacy of Paroxetine as an Adjuvant Therapy in Rheumatoid Arthritis Patients: A Randomized Controlled Study

Khlood Mohammad Aldossary,1 Mahmoud S Abdallah,2,3 Esraa M Mosalam,3,4 Noha Kamal,2 Dalia S Saif,5 Sahar Abdel-Rahman Elsayed,6 Naglaa Afifi,7 Haitham G Zakaraia,2 Mohannad O Khrieba,8 Mostafa M Bahaa8,9 1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 2Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City (USC), Sadat City, Menoufia, Egypt; 3Department of PharmD, Faculty of Pharmacy, Jadara University, Irbid, Jordan; 4Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Kom, Egypt; 5Department of Rheumatology, Rehabilitation, and Physical Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt; 6Department of Rheumatology, Rehabilitation, and Physical Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Internal Medicine and Rheumatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Pharmacy Practice Department, Faculty of Pharmacy, Horus University-Egypt (HUE), New Damietta, Egypt; 9Pharmacy Practice Department, Faculty of Pharmacy, Mansoura National University, Gamasa, EgyptCorrespondence: Mostafa M Bahaa, Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt, Email [email protected]; [email protected]: Despite advances in pharmacological interventions for rheumatoid arthritis (RA), a subset of patients continues to experience disease activity, highlighting the need for adjunctive therapeutic strategies.Objective: To assess the therapeutic efficacy of paroxetine when administered as adjuvant therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA).Methods: In this randomized, double-blind, clinical trial, one hundred patients were randomized in 1:1 ratio to receive either csDMARDs including methotrexate plus placebo (control group) or paroxetine (paroxetine group). The primary endpoint was the change in Disease Activity Score using 28 joint counts (DAS-28) [Tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP), visual analogue scale (VAS)] at three months. Secondary endpoints included multidimensional health assessment questionnaire [morning stiffness (MS), pain, fatigue, physical functioning (PF)].Results: After treatment, both groups demonstrated significant within-group improvements in TJC, SJC, VAS, and DAS-28, with superior improvements observed in the paroxetine group (p = 0.016, 0.0006, 0.03, and 0.005, respectively). CRP showed no significant change in the control group (p = 0.933). Paroxetine group showed significant reductions in MS, pain, and fatigue (p = 0.024, 0.03, and 0.006, respectively) compared with the control group, while PF were significant within groups but not between groups (p = 0.208). Adverse events were comparable, except for a higher incidence of decreased libido in the paroxetine group.Conclusion: Adjunctive paroxetine significantly improved clinical and patient-reported outcomes in mild and moderate RA patients and was generally well tolerated, supporting its potential as an effective adjunctive therapy. The relatively small single-center sample, the exclusion of severe RA patients, the short disease duration, the low seropositivity, absence of mental health assessment, the possibility of overlapping with secondary pain mechanisms (eg, central sensitization or early fibromyalgia features) may limit the generalizability of the findings to broader and more diverse patient populations.Trial Registration Identifier: NCT06231745.Keywords: rheumatoid arthritis, paroxetine, DAS-28, CRP, disease-modifying antirheumatic drugs, randomized controlled trial