Herpes zoster (HZ) is characterized by a painful dermatomal rash and significantly affects quality of life, with acute pain increasing the risk of postherpetic neuralgia. Although early antiviral therapy limits viral replication, its analgesic effect is insufficient, and many patients experience inadequate relief despite stepwise use of non-opioids and opioids. Recent attention has focused on the potential role of antidepressants, which have central antinociceptive property and may offer analgesic benefits by modulating central nervous system pain pathways through increased serotonin and norepinephrine availability. Therefore, investigators hypothesize that tulodesvenlafaxine may effectively reduce the severity of HZ pain without significantly increasing adverse events.

Inclusion Criteria:

• 1. Ages more than 18 years;
• 2. Patients with onset of HZ rash less than 90 days;
• 3. Experiencing moderate to severe HZ pain with an average pain score of at least 4 on a Numeric Rating Scale (NRS, 0 = no pain, 10 = worst possible pain);
• 4. Aspartate aminotransferase and alanine aminotransferase levels less than twice the upper limit of normal;
• 5. Estimated glomerular filtration rate of 30 mL/min per 1.73 m2 or higher;
• 6. Willing to sign the informed consent form and possessing sufficient cognitive and language abilities to comply with all the study requirements.

Exclusion Criteria:

• 1. History of taking tulodesvenlafaxine;
• 2. Patients with evidence of cutaneous or visceral dissemination of HZ infection (cutaneous dissemination is defined as more than 20 discrete lesions outside adjacent dermatomes) or ocular involvement of HZ;
• 3. History of intolerance or hypersensitivity to any active components or excipient of the tulodesvenlafaxine;
• 4. History of systemic immune diseases, organ transplantation, or cancers;
• 5. Pregnancy or breastfeeding;
• 6. Suffering from acute or chronic pain disorders other than HZ.

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.