Venlafaxine as Adjunct Therapy in Rheumatoid Arthritis

The Effect of Venlafaxine as an Adjunct Therapy on The Clinical Outcome of Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of the joints, leading to pain, swelling, disability, and reduced quality of life. Current therapies, although effective, may have limited efficacy or tolerability in some patients. Biological DMARDs are often associated with adverse effects, including increased risk of serious infections and heart failure. Long-term use may also increase the risk of malignancies. These limitations, together with their high cost. Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), has shown potential anti-inflammatory properties in addition to its antidepressant effects. This study aims to evaluate the efficacy and safety of venlafaxine as an adjunct therapy in the management of rheumatoid arthritis.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: venlafaxine extended-release (XR); Other: Standard conventional Rheumatoid Arthritis Therapy

Detailed Description

Eligible patients will be randomly assigned using block randomization to one of the following groups:

Venlafaxine group: 35 patients will receive the standard RA treatment in addition to venlafaxine extended-release (XR) initiated at a dose of 75 mg/day for one week to ensure tolerability, followed by an increase to 150 mg/day, which will be maintained for the duration of the study (12 weeks) The control group: 35 patients will receive the standard treatment of RA, which will be maintained for the duration of the study (12 weeks).

At baseline the following data will be collected from the patient :

Age - Gender- Body mass index (BMI) - Medical history- Medication history- Smoking status- Disease duration- Dose of corticosteroids if present.

Efficacy evaluation Serum CRP and ESR will be assessed at baseline and after 3 months using routine analysis

• Disease activity using DAS-28-CRP Disease severity will be assessed using DAS-28-CRP at baseline and after 3 months Safety assessment All patients will be assessed on a monthly basis during clinic visits and on a weekly basis during phone calls to assess the adverse effects of venlafaxine. All patients will be educated about the study protocol and will be required to report the occurrence of any of them.

Serum biomarker A blood ample will be withdrawn from each patient at baseline and after 3 month and the separated sera will be stored at -80o C till analysis. These sera will be used to assess the level of VEGF using commercial ELISA kits.

Quality of life assessment using health assessment questionnaire (HAQ-DI)

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara Ahmed Ibrahim Ahmed, Teaching Assistant at Faculty; Phone Number: 02 01016069393; Email: Sara.ahmed18@pharma.asu.edu.eg
• Study Contact Backup: Name: Hend Magraby Magraby, Associate Professor of Rheumat; Phone Number: 01114911897; Email: hendms@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients with definite RA according to ACR/ EULAR 2010 criteria.
• Patients on stable DMARDs+/- steroid regimen for at least 6 months.
• Patients with moderate to high disease activity (DAS28 ≥ 3.2) despite treatment

Exclusion Criteria:

• Patients receiving biologics or targeted DMARDs
• Known hypersensitivity to venlafaxine or any of its components.
• Concurrent Use of MAOIs
• Women who are pregnant or breastfeeding.
• Uncontrolled hypertension
• Unstable Heart Conditions
• Patients receiving any other anti-depressant
• Psychiatrically unstable patients as indicated by a history of psychosis or mania, current suicidal ideation, current substance abuse or dependence.
• Renal dysfunction (creatinine clearance <60 mL/min)
• Hepatic dysfunction (ALT and AST more than 3 times upper normal limits)
• Patients with active major bleeding or high risk of bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venlafaxine Group; Venlafaxine extended-release (XR) initiated at a dose of 75 mg/day for one week to ensure tolerability, followed by an increase to 150 mg/day, which will be maintained for the duration of the study (12 weeks)	Drug: venlafaxine extended-release (XR); 35 patients will receive the standard RA treatment in addition to venlafaxine extended-release (XR) initiated at a dose of 75 mg/day for one week to ensure tolerability, followed by an increase to 150 mg/day, which will be maintained for the duration of the study (12 weeks)
Active Comparator: Control Group (Standard Therapy); The standard treatment for Rheumatoid Arthritis, which will be maintained for the entire 12-week study period [Standard treatment of RA includes one or more conventional DMARDs (methotrexate, hydroxychloroquine, leflunomide, sulfasalazine) with or without low dose corticosteroids].	Other: Standard conventional Rheumatoid Arthritis Therapy; 35 patients will receive the standard treatment of RA, which will be maintained for the duration of the study (12 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disease Activity Score 28 (DAS28-CRP)	Disease severity will be assessed using DAS-28-CRP Disease activity will be assessed using the Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP), a validated composite index that includes tender joint count (28 joints), swollen joint count (28 joints), C-reactive protein (CRP), and patient global assessment of health. The DAS28-CRP score ranges approximately from 0 to 9.4, with higher scores indicating higher disease activity and worse outcomes.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-reactive protein (CRP)	Serum C-reactive protein (CRP) levels will be measured as an indicator of systemic inflammation. CRP is expressed in mg/L, with higher values indicating increased inflammatory activity.	Baseline and 3 months
Change in erythrocyte sedimentation rate (ESR)	Erythrocyte sedimentation rate (ESR) will be measured as a marker of inflammation. ESR is expressed in mm/hour, with higher values indicating increased inflammatory activity.	Baseline and 3 months
Change in serum vascular endothelial growth factor (VEGF)	To investigate the change in serum vascular endothelial growth factor (VEGF) levels before and after venlafaxine treatment. A blood sample will be withdrawn from each patient at baseline and after 3 month and the separated sera will be stored at -80o C till analysis. These sera will be used to assess the level of VEGF using commercial ELISA kits.	at baseline and after 3 months.
safety and tolerability of venlafaxine	To evaluate the safety and tolerability of venlafaxine through monitoring and documentation of potential adverse events during the study period	at baseline and after 3 months.
Health assessment questionnaire HAQ-DI.	It consists of 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities, with 2-3 questions per domain. Each question is scored from 0 (no difficulty) to 3 (unable to do). The domain score is determined by the highest response within that domain. If an assistive device or help from another person is required, the minimum score for that domain is 2 (unless the score is already ≥ 2). The total HAQ-DI score is calculated by summing the 8 domain scores and dividing by 8. The final score ranges from 0 to 3, with higher scores indicating greater disability.	at baseline and after 3 months.

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: sara ahmed, Bsc, Faculty of Pharmacy, ASU

Publications and helpful links

General Publications

• Arleevskaya, M., Takha, E., Petrov, S., Kazarian, G., Novikov, A., & Larionova, R. (2021). Causal risk and protective factors in rheumatoid arthritis : A genetic update. Journal of Translational Autoimmunity, 4, 100119. https://doi.org/10.1016/j.jtauto.2021.100119 BASSEL EL-ZORKANY, M.D., W. A. M. D. ., & LOBNA A. MAGED, M.D., N. E.-G. M. D. . M. (2023). Evaluation of Rheumatoid Arthritis Knowledge among a Cohort of 1004 Healthy Egyptians. The Medical Journal of Cairo University, 91(03), 225-0. https://doi.org/10.21608/mjcu.2023.307506 Bullock, J., Rizvi, A. A., Saleh, A. M., & Ahmed, S. (2018). Rheumatoid Arthritis : A Brief Overview of the Treatment. 33328, 501-507. https://doi.org/10.1159/000493390 Chen, C. Y., Yeh, Y. W., Kuo, S. C., Liang, C. S., Ho, P. S., Huang, C. C., Yen, C. H., Shyu, J. F., Lu, R. B., & Huang, S. Y. (2018). Differences in immunomodulatory properties between venlafaxine and paroxetine in patients with major depressive disorder. Psychoneuroendocrinology, 87(325), 108-118. https://doi.org/10.1016/j.psyneuen.2017.10.009 Chen, L., Zeng, X., Zhou, S., Gu, Z., & Pan, J. (2022). Correlation Between Serum Tumor Necrosis Factor-Alpha , Serum Interleukin-6 and White Matter Integrity Before and After the Treatment of Drug-Naïve Patients With Major Depressive Disorder. 16(July), 1-9. https://doi.org/10.3389/fnins.2022.948637 El Meidany, Y. M., El Gaafary, M. M., & Ahmed, I. (2003). Cross-cultural adaptation and validation of an Arabic Health Assessment Questionnaire for use in rheumatoid arthritis patients. Joint Bone Spine, 70(3), 195-202. https://doi.org/10.1016/S1297-319X(03)00004-6 F., W. (1989). The Health Assessment Questionnaire (HAQ) Disability Index (DI) Of The Clinical Health Assessment Questionnaire (Version 96.4). Arthritis Rheum., 32(Di), 2-7. Gharib, M., Elbaz, W., Darweesh, E., & Sabri, N. A. (2021). Ef fi cacy and Safety of Metformin Use in Rheumatoid Arthritis : A Randomized Controlled Study. 12(September), 1-9. https://doi.org/10.3389

Study record dates

Study Major Dates

• Study Start (Estimated): March 26, 2026
• Primary Completion (Estimated): October 26, 2026
• Study Completion (Estimated): December 26, 2026

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Quality of life; Rheumatoid arthritis; Venlafaxine; Vascular endothelial growth factor (VEGF); Disease activity score (DAS28)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: REC # 407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to institutional policies and to protect participant confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No