Comment from Rokuro Hama

Petition to Add a Black Boxed Warning that SSRI Antidepressants are Contraindicated for Pregnant Women due to Reproductive Toxicities, Especially with Infants Mortality and Alteration of Fetal Brain Development. Dear Commissioner Makary, I am a Japanese medical doctor who had been a practicing physician of internal medicine since 1969 for 28 years and have been publishing ISDB-full-membership Drug Bulletins ("The Informed Prescriber" for professionals since 1986 for 30 years, "Kusuri-no-Check" for public since 2001 for 14 years and "MedCheck" for public and professionals since 2015 for 12 years both in Japanese and in English: https://medcheckjp.org/). It is widely recognized that serotonin reuptake inhibitors (SRIs or SSRI) cause harms on the reproductive systems including teratogenicity. However, it is less known that they cause dose-dependent increase of neonatal death at the lowest clinical human equivalent dose probably due to toxic and/or withdrawal syndrome and withdrawal persistent pulmonary hypertension in newborns. I wrote an article on this topic in 2009 based on the paroxetine's Summary Technical Documentation (STED) which is a summary of the application dossier for marketing authorization prepared by the pharmaceutical company containing clinical and animal studies. They are publicly available (https://www.pmda.go.jp/PmdaSearch/iyakuSearch). I translated the article "Reproductive Toxicities of Paroxetine" into English (available free at MedCheck in English No 33 2025) because even today, it is not well known that paroxetine caused dose-dependent increase of neonatal death at the lowest clinical human equivalent dose. Based on the analysis on the fetal brain toxicity of SRIs by Dr Adam Urato and Kelli Foulkrod (https://t.co/y0OKHi6EA4) and my analysis on the dose-dependent increase of neonatal death at the lowest clinical human equivalent dose of paroxetine, I request Food and Drug Administration to Add a Black Boxed Warning that SSRI Antidepressants are Contraindicated for Pregnant Women due to Reproductive Toxicities, Especially with Infants Mortality and harm on Fetal Brain Development. Please see attached files for ＃ Full version of petition by HAMA 1) The article "Reproductive Toxicities of Paroxetine" in MedCheck in English No 33 (Aug 2025). it is also available at: https://medcheckjp.org/wp-content/uploads/2025/08/Eng-no-33.pdf 2) A related article on paroxetine inducing hostility/agitation in Phase 1 studies in MedCheck in English No 31 (Dec 2024). It is also available at: https://medcheckjp.org/wp-content/uploads/2025/01/Eng-no-31.pdf HAMA, Rokuro MD Director "Japan Institute of Pharmacovigilance" publishing ISDB-full-membership Drug Bulletin0 ISDB: International Society of Drug Bulletin: https://www.isdbweb.org/ "MedCheck" https://medcheckjp.org/ see also http://npojip.org/