THE ASSOCIATION BETWEEN EARLY INITIATION OF ANTICONVULSANTS AND/OR ANTIDEPRESSANTS/ANTI-ANXIETY MEDICATIONS AND THE RISK OF POST-HERPETIC NEURALGIA IN PATIENTS 50 YEARS AND OLDER WITH NEWLY DIAGNOSED HERPES ZOSTER IN CALIFORNIA, USA
Authors: Tseng *Hung Fu , Luo Yi , Zheng Chengyi , Lin I-Chun , Daily Leticia Vela , Song Jeannie 
Published: February 2025

Abstract

Background
Herpes zoster (HZ)-associated pain causes a significant burden on patients and healthcare resources. Treatment options for post-herpetic neuralgia (PHN) is limited, and treatment course could be refractory. The consensus is that preventing the progression of acute zoster pain to PHN is preferable to treating PHN itself. In clinical practice, anticonvulsants such as gabapentin and pregabalin have been reported to reduce the severity and duration of acute pain from HZ and lowered the risk of PHN. Tricyclic antidepressants, including amitriptyline, nortriptyline, desipramine, and imipramine, have also demonstrated efficacy in treating PHN symptoms. Initiating amitriptyline treatment shortly after the HZ onset in those at a higher risk of PHN has been suggested. However, the clinical application of these medications in preventing PHN is limited due to insufficient data.

Aims and Objectives
To evaluate the association between early initiation of anticonvulsants and/or antidepressants/anti-anxiety medications and the development of PHN in HZ patients 50 years and older

Methods
We conducted a cohort study at Kaiser Permanente Southern California. The cohort included incident HZ patients, identified by diagnostic codes plus use of antiviral medications, aged 50 years and older who were diagnosed between 4/1/2018 and 12/31/2020 with no history of using anticonvulsants, antidepressants, and anti-anxiety medications within 180 days prior to HZ diagnosis. The exposure was defined as having initiated use of anticonvulsants or antidepressants/anti-anxiety medications, or both categories within one month after HZ diagnosis. The outcome, PHN, was defined as HZ-related pain persisting &gt;3 months after HZ diagnosis. Targeted chart review was conducted to identify PHN from encounter records 90-180 days after the initial HZ diagnosis. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) associated with each exposure category comparing to the reference category, controlling for age, sex, race/ethnicity, zoster vaccination history, immunosuppression conditions, comorbidities, healthcare utilization history, and continuous use of anticonvulsants, antidepressants, and anti-anxiety medication within 31-90 days after HZ diagnosis.

Results
There were 7865 incident HZ patients identified. Among them, 2829 were excluded due to the use of anticonvulsants, antidepressants, or anti-anxiety medications within 180 days prior to HZ diagnosis. Of the remaining 5036 HZ patients, 300 (5.96%) developed PHN. The odds ratio associated with initiating anticonvulsants, antidepressants/anti-anxiety medications, or both categories within one month after HZ diagnosis, was 0.95 (95% CI: 0.62 - 1.43), 1.22 (95% CI: 0.55 - 2.69), and 2.41 (95% CI: 1.25 - 4.62), respectively.

Discussion & Conclusion
We find no evidence supporting a lower risk of PHN associated with early initiation of anticonvulsant or antidepressant/anti-anxiety medications in adults 50 years and older. The lack of protective effect may partly be due to the possibility that HZ patients who had severe acute zoster pain or were suspected to be at a higher risk of PHN would initiate these medications earlier. A detailed measure of baseline severity and physician prescribing behavior would be helpful to control the potential confounding by indication.

References
1.Johnson, Robert W., and Andrew SC Rice. "Postherpetic neuralgia." New England Journal of Medicine 371.16 (2014): 1526-1533.
2.Saguil, Aaron, et al. "Herpes zoster and postherpetic neuralgia: prevention and management." American family physician 96.10 (2017): 656-663.
3.Finnerup, Nanna B., et al. "Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis." The Lancet Neurology 14.2 (2015): 162-173.
4.Bulilete, Oana, et al. "Efficacy of gabapentin for the prevention of postherpetic neuralgia in patients with acute herpes zoster: A double blind, randomized controlled trial." PLoS One 14.6 (2019): e0217335.
5.John Schutzer-Weissmann &Paul Farquhar-Smith (2017) Post-herpetic neuralgia – a review of current management and future directions, Expert Opinion on Pharmacotherapy, 18:16, 1739-1750