Chronic non-specific low back pain is the leading cause of productivity loss and disability worldwide, constituting a major public health challenge. This study aims to systematically evaluate and compare the role of the antidepressant drug toludesvenlafaxine in chronic non-specific low back pain, which is of critical importance for optimising clinical practice and developing precise, individualised treatment regimens.

Inclusion Criteria:

• Adults aged 18 to 75 years.
• Diagnosis of chronic nonspecific low back pain, defined as pain located below the costal margin and above the inferior gluteal folds, lasting for more than 3 months, without a specific pathological cause.
• Moderate to severe pain, defined as a Numerical Rating Scale score of 3 or higher.
• Able to understand the study procedures and sign written informed consent.

Exclusion Criteria:

• Low back pain caused by a known specific pathological condition, including but not limited to fracture, malignancy, infection, inflammatory disease, or other identifiable structural or systemic causes.
• Major comorbidities that may interfere with study outcomes or represent contraindications to the study medication.
• Current or previous diagnosis of depression, regardless of whether treatment was received.
• Current or previous use of antidepressant medication.
• Current use of opioid analgesics.
• Pregnancy, breastfeeding, or planned pregnancy during the study period.
• Known allergy, hypersensitivity, or contraindication to toludesvenlafaxine.
• History of psychosis or other major psychiatric disorders.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures and appendices) are available. Derived data supporting the findings of this study are available from the corresponding author Fang Luo on request.