A Response to Letter to the Editor Regarding “The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis”

Sep 30, 2026

This response letter addresses comments on a prior publication analyzing incident herpes zoster (HZ) risk among individuals with depressive disorders using German healthcare claims data. The authors thank the letter’s contributors, clarify that sex distribution differences reflect database prevalence patterns and explain the absence of sex-stratified HZ incidence ratio analyses. They further discuss depression severity findings, where mild/unspecified depression showed slightly higher HZ incidence than severe depression, and note that post hoc subgroup matching prevents direct statistical comparisons. Additional real-world evidence integrating clinical severity scales, antidepressant use, and immunization status is recommended.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

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Response Letter

Sex distribution and stratified analyses

Depression severity and HZ incidence

Infect Dis Ther (2026) 15:381–383 [https://doi.org/10.1007/s40121-025-01237-9](https://doi.org/10.1007/s40121-025-01237-9) LETTER A Response to: Letter to the Editor Regarding “The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis” Pavo Marijic · Julian Witte · Bastian Surmann · Manuel Batram · Johannes Hain · Christian Rauschert · Marie Nishimwe · Christian Maihöfner · Helmut Schöfer · Philipp Stahl · Ursula Marschall · Christiane Hermann Received: July 23, 2025 / Accepted: September 12, 2025 / Published online: November 10, 2025 © GSK Plc. 2025, modified publication 2025 Keywords: Depression; Depression severity; Gender difference; Germany; Healthcare claims data; Herpes zoster; Incidence rates; Risk factors Dear Editor, We sincerely thank the authors of the letter, K-F Liao and S-W Lai, for their thoughtful and This reply refers to the comment available online at [https://doi.org/10.1007/s40121-025-01236-w](https://doi.org/10.1007/s40121-025-01236-w). P. Marijic (*) · J. Hain · C. Rauschert GSK, Munich, Germany [e-mail: pavo.x.marijic@gsk.com](e-mail: pavo.x.marijic@gsk.com) J. Witte · B. Surmann · M. Batram Vandage, Bielefeld, Germany M. Nishimwe GSK, Rueil Malmaison, France C. Maihöfner General Fürth Hospital, University of Erlangen, Fürth, Germany H. Schöfer Wiesbaden, Germany P. Stahl Practice Meinecke & Stahl, Burg, Germany U. Marschall Department Medicine/Health Care Research, BARMER, Wuppertal, Germany C. Hermann Justus-Liebig University Giessen, Giessen, Germany constructive comments regarding our recent publication entitled “The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis” which compares the risk of incident herpes zoster (HZ) in individuals with and without depressive disorders [1] . We appreciate the opportunity to address the points which were raised and provide further context to our findings. SEX DISTRIBUTION AND STRATIFIED ANALYSES As correctly noted, the majority of individuals included in our study were female (70%), reflecting both the higher prevalence of depression among females and the gender distribution observed in our underlying German claims database (“real-world dataset”) . As stated in our manuscript, a higher prevalence of depression in female individuals than in male individuals has been reported previously [2] . We acknowledge that no sex-stratified analyses for HZ incidence rate ratios were conducted and this might limit the generalizability of our findings to males. However, our primary goal was to estimate the average population-level risk under realworld conditions and not to infer sex-specific mechanisms. We agree that analyses stratified by sex could provide valuable insights, particularly given the evidence for sex-based differences in both depression pathophysiology and immune responses. The factors influencing the observed prevalence in male and female patients are largely unknown; accordingly, we have addressed this aspect in the Discussion section of our findings, which points towards future research: “it is unknown whether the lower incidence of depression in men is a true gender effect or due to underdiagnosis or other, unknown factors [2] .” DEPRESSION SEVERITY AND HZ INCIDENCE The second point regarding the observed HZ incidence across depression severity subgroups is both important and complex. As noted, individuals with mild or unspecified depression exhibited slightly higher HZ incidence rates than those with severe depression (mild depression: 10.81 cases per 1000 patient-years [95% confidence interval (CI): 10.64; 10.99]; severe depression: 9.83 cases per 1000 patient-years [95% CI : 9.69; 9.98]) . This pattern might appear counterintuitive from a biological perspective, as more severe depression is generally associated with greater physiological dysregulation, including potential immune suppression [3] . Note, however, t

FAQs

Why did the study not perform sex-stratified HZ analyses for risk ratios?

The authors did not conduct sex-stratified analyses and state this could limit generalizability to males, because the study aimed to estimate average population-level risk under real-world conditions rather than sex-specific mechanisms.

How did depression severity relate to HZ incidence in the reported results?

Mild or unspecified depression showed slightly higher HZ incidence rates than severe depression, with rates reported per 1000 patient-years and corresponding confidence intervals.

Why can’t the depression severity subgroups be directly compared using the reported risk ratios or incidences?

Each severity subgroup was analyzed separately after post hoc matching, and individuals could appear in multiple groups over time as depression conditions changed, so magnitudes between subgroups cannot be compared descriptively or statistically.

Sep 30, 2026

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