The Analgesic Efficacy and Safety of Venlafaxine for Prevention of Postherpetic Neuralgia in Patients With Acute Herpes Zoster

The Analgesic Efficacy and Safety of Oral Medications (Venlafaxine) for Prevention of Postherpetic Neuralgia in Acute Herpes Zoster

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ) and represents a major clinical challenge due to its chronicity and impact on quality of life. Current treatments for acute HZ pain have limited efficacy in preventing PHN, highlighting the need for effective preventive strategies targeting early pathophysiological mechanisms. Venlafaxine as a plausible and clinically relevant candidate for early intervention to prevent the transition from acute HZ pain to PHN.

Study Overview

• Status: Recruiting
• Conditions: Pain; Herpes Zoster; Postherpetic Neuralgia
• Intervention / Treatment: Drug: Venlafaxine combined conventional therapy; Drug: Conventional therapy

• Study Type: Interventional
• Enrollment (Estimated): 832
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fang Luo; Phone Number: 13611326978; Email: 13611326978@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital, Beijing, Beijing 100070
    • Contact: Fang Luo; Phone Number: 13611326978; Email: 13611326978@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Ages more than 18 years;
• 2. Patients with onset of HZ rash less than 30 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. HZ with head, neck, ocular, mucous membrane, cranial nerve, or central nervous system involvement or generalized HZ;
• 2.Known hypersensitivity to venlafaxine;
• 3.History of major depressive disorder requiring antidepressant therapy;
• 4.History of systemic immune diseases, organ transplantation, or cancers;
• 5.Pregnancy or lactation;
• 6.Presence of acute or chronic pain disorders other than HZ.

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
Active Comparator: Conventional therapy group	Drug: Conventional therapy; The control group will receive conventional therapy alone before 90 days after rash onset. After 90 days from rash onset, treatment will be standardized across both groups. Participants who develop persistent pain consistent with PHN will receive guideline-based management, including gabapentinoids, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and topical agents such as lidocaine or capsaicin, as clinically indicated.
Experimental: Venlafaxine combined with conventional therapy group	Drug: Venlafaxine combined conventional therapy; Venlafaxine will be initiated at 75 mg once daily and titrated based on pain response and tolerability before 90 days after rash onset. All participants will receive standardized analgesic management following the World Health Organization pain ladder. In addition, the group will contain conventional treatment for HZ, including NSAIDs, opioids, antiviral drugs and so on. After 90 days from rash onset, treatment will be standardized across both groups. Participants who develop persistent pain consistent with PHN will receive guideline-based management, including gabapentinoids, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and topical agents such as lidocaine or capsaicin, as clinically indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of PHN	PHN will be defined as persistent pain in the affected dermatome at 90 days after rash onset that is clinically meaningful, operationalized as an average pain score ≥ 3 on the NRS.	at 90 days after rash onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain Scale	Neuropathic pain characteristics will be assessed using the Neuropathic Pain Scale in participants with developing PHN. The Neuropathic Pain Scale consists of 10 numeric rating items, each scored from 0 to 10, with higher scores indicating greater neuropathic pain severity. The scale assesses pain intensity, unpleasantness, and 8 specific pain qualities, including sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain.	at or after 90 days following rash onset
The average daily pain intensity	The numeric rating scale (NRS) score is a way to quantify the degree of subjective feelings such as pain using numbers. Generally, 0 represents no pain, and 10 represents the most severe pain. A higher score indicates more severe pain.	at weeks 1, 2, 4, 8, 12, 24, and 52
The worst numeric rating scale score	The numeric rating scale (NRS) score is a way to quantify the degree of subjective feelings such as pain using numbers. Generally, 0 represents no pain, and 10 represents the most severe pain. A higher score indicates more severe pain.	at weeks 1, 2, 4, 8, 12, 24, and 52
Proportion of Patients Achieving Pain Reduction	The proportion of patients achieving a ≥ 50% and ≥ 30% reduction in mean baseline pain intensity	at weeks 1, 2, 4, 8, 12, 24, and 52
Average weekly consumption of each analgesic class		at weeks 4, 8, 12, 24, and 52
Herpes Zoster Severity of Illness Index	The HZSOI is a severity-by-duration measure of overall pain burden associated with HZ and is typically calculated as the area under the curve of the worst pain scores over a defined period after rash onset.	at weeks 1, 2, 4, 8 and 12
The 12-item Short-Form Health Survey (SF-12) score	The SF-12 score assesses the health-related quality of life, capturing preferences across various health states. It assesses 8 dimensions: physical functioning, physical role limitations due to physical health, bodily pain, general health, vitality, social functioning, emotional role limitations due to emotional problems, and mental health. Scores range from 0 to 100 for each dimension, with higher scores indicating better health status.	at weeks 4, 8, 12, 24, and 52
The Medical Outcomes Study Sleep Scale (MOS)	The MOS is a questionnaire comprising 12 items that assess various aspects of sleep using a 6-point ordinal scale (1 indicating permanence and 6 indicating absence).	at weeks 4, 8, 12, 24, and 52
Adverse events	The incidence and proportion of adverse events will be recorded and categorized as mild, moderate, severe, or life-threatening. AEs are defined as events that arise during treatment, were absent before treatment, or worsen relative to the pretreatment state.	Through study completion, an average of 52 weeks

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Xiangya Hospital of Central South University; Zhongnan Hospital

Publications and helpful links

Helpful Links

• Rosamilia LL. Herpes Zoster Presentation, Management, and Prevention: A Modern Case-Based Review. Am J Clin Dermatol. 2020;21(1):97-107.
• Liu Y, Xiao S, Li J, Long X, Zhang Y, Li X. A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain. Pain Physician. 2023;26(4):337-46.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Infections; Virus Diseases; Peripheral Nervous System Diseases; DNA Virus Infections; Herpesviridae Infections; Neuralgia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Herpes Zoster; Neuralgia, Postherpetic
• Other Study ID Numbers: KY2025-369-02-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

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