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The authors highlight that although sex distributions were similar between groups, ~70% of participants were female and sex-stratified analyses were not performed, limiting generalizability to men. They also question subgroup results showing higher HZ incidence in unspecified or mild depression and lower incidence in severe depression, suggesting missing explanations, stratified analyses, sensitivity checks, and discussion of antidepressant effects. The letter calls for further real-world evidence.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/letter-to-the-editor-regarding-the-risk-of-herpes-zoster-in-patients-with-depressive-disorders-a-german-claims-database-analysis/459669/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/letter-to-the-editor-regarding-the-risk-of-herpes-zoster-in-patients-with-depressive-disorders-a-german-claims-database-analysis/459669.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-07","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What methodological limitations does the letter point out about the original study?","Question",{"text":112,"@type":113},"It notes that ~70% of participants were female and that sex-stratified analyses of herpes zoster incidence rates or incidence rate ratios were not conducted, limiting conclusions for male individuals.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why does the letter challenge the subgroup findings by depression severity?",{"text":117,"@type":113},"It reports that mild or unspecified depression showed the highest HZ incidence while severe depression showed the lowest, which contradicts biological expectations that more severe depression would increase immunosuppression and HZ risk.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence does the letter request to clarify the relationship between depression severity and HZ risk?",{"text":121,"@type":113},"It calls for additional real-world evidence and emphasizes the need for detailed explanations, stratified analyses, and sensitivity checks regarding antidepressant use and immune-related mechanisms.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459669,1790756553,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":129,"read_time":24,"preview_page_count":4},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Infect Dis Ther (2026) 15:385–386  \n[https://doi.org/10.1007/s40121-025-01236-w](https://doi.org/10.1007/s40121-025-01236-w)  \nLETTER  \nLetter to the Editor Regarding “The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis”  \nKuan‑Fu Liao · Shih‑Wei Lai  \nReceived: April 27, 2025 / Accepted: September 12, 2025 / Published online: November 10, 2025 © The Author(s) 2025  \nKeywords: Depression; Herpes zoster; Incidence  \nDear Editor,  \nAfter reading the study by Marijic et al. [1], sev‑ eral methodological questions warrant further discussion. First, although matching achieved similar sex distributions between groups, approximately 70% of participants were female [1], reflecting known epidemiology but limit‑ ing the generalizability of the findings to male individuals. Notably, the authors did not con‑ duct sex‑stratified analyses of herpes zoster (HZ) incidence rates or incidence rate ratios, missing  \nThis comment refers to the article available online at [https://doi.org/10.1007/s40121](https://doi.org/10.1007/s40121)‑025‑01116‑3.  \nK.‑F. Liao  \nCollege of Medicine, Tzu Chi University, Hualien, Taiwan  \nK.‑F. Liao  \nDivision of Hepatogastroenterology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung, Taiwan  \nS.‑W. Lai (*)  \nSchool of Medicine, China Medical University, Taiwan, and Department of Family Medicine, China Medical University Hospital, No 2, Yu‑De Road, Taichung City 404327, Taiwan  \ne‑[mail: wei@mail.cmuh.org.tw](mail: wei@mail.cmuh.org.tw)  \nan opportunity to explore potential sex‑specific differences in risk, especially given that both depression and immune responses can vary by sex. Second, the subgroup analysis revealed an unexpected pattern: individuals with unspeci‑ fied or mild depression had the highest HZ incidence rates (11.21 and 10.81 cases per 1000 person‑years, respectively), while those with severe depression had the lowest incidence rate (9.83 cases per 1000 person‑years) [1] . These findings contradict biological expectations, where severe depression would be anticipated to introduce greater immunosuppression and thus higher HZ risk [2] . Although the authors speculated that antidepressant use might modu‑ late immune function, no detailed explanation, stratified analysis, or sensitivity checks were pro‑ vided, leaving an important gap in interpreting the relationship between depression severity and HZ risk.  \nWe greatly appreciate the valuable contribu‑ tion of Marijic et al. to this important issue. We think that further real‑world evidence is needed to clarify these observations.  \nAuthor Contributions. Kuan‑Fu Liao initi‑ ated the conception of the article. Shih‑Wei Lai initiated the draft of the article and approved the final draft.  \nFunding. No funding or sponsorship was received for this study or publication of this article.  \nDeclarations  \nConflict of Interest. Kuan‑Fu Liao and Shih‑ Wei Lai disclose that they have no conflict of interest.  \nEthical Approval. This article is based on previously conducted studies and does not con‑ tain any new studies with human participants or animals performed by any of the authors.  \nOpen Access. This article is licensed under a Creative Commons Attribution‑NonCommercial 4.0 International License, which permits any non‑commercial use, sharing, adaptation, distri‑ bution and reproduction in any medium or for‑ mat, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the  \narticle’s Creative Commons licence, unless indi‑ cated otherwise in a credit line to the material. If material is not included in the article’s Crea‑ tive Commons licence and your intended use isnot permitted by statutory regulation or exceeds the permitted use, you will need to obtain per‑ mission directly from the copyright holder. To view a ","cbCainpwoGwc0Qe4","https://ap.wps.com/l/cbCainpwoGwc0Qe4","pdf",152457,"English","# Letter to the Editor\n## Methodological concerns on sex distribution and generalizability\n## Questions about subgroup patterns by depression severity\n## Need for real-world evidence and interpretation gaps","[{\"question\":\"What methodological limitations does the letter point out about the original study?\",\"answer\":\"It notes that ~70% of participants were female and that sex-stratified analyses of herpes zoster incidence rates or incidence rate ratios were not conducted, limiting conclusions for male individuals.\"},{\"question\":\"Why does the letter challenge the subgroup findings by depression severity?\",\"answer\":\"It reports that mild or unspecified depression showed the highest HZ incidence while severe depression showed the lowest, which contradicts biological expectations that more severe depression would increase immunosuppression and HZ risk.\"},{\"question\":\"What evidence does the letter request to clarify the relationship between depression severity and HZ risk?\",\"answer\":\"It calls for additional real-world evidence and emphasizes the need for detailed explanations, stratified analyses, and sensitivity checks regarding antidepressant use and immune-related mechanisms.\"}]","Letter to the Editor Regarding “The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis” | PDF"]