**5. Conclusions**

Overall, most adults with DS and depression responded to a 12-week course of SSRI treatment, and some tolerated long-term use. Although seven of the 11 patients in the study had no adverse effects reported in their psychiatric notes, several experienced behavioral activation and one experienced mania. We believe our findings warrant a future prospective randomized placebo-controlled study of SSRIs in adults with DS.

**Author Contributions:** Conceptualization, R.P.T., M.L.P., C.J.M. and C.T.R.; methodology, R.P.T., M.L.P., C.J.M. and C.T.R.; formal analysis, C.T.R.; investigation, R.P.T., M.L.P., C.J.M., C.T. and C.T.R.; data curation, R.P.T., C.T.; writing—original draft preparation, R.P.T.; writing—review and editing, R.P.T., M.L.P., C.J.M., C.T. and C.T.R. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was funded, in part, by the Nancy Lurie Marks Family Foundation.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Mass General Brigham (protocol code 2021P000640 and March 12, 2021).

**Informed Consent Statement:** Patient consent was waived due because requiring consent would lead to years of delay, incomplete information, biased analyses, and would result in less utility of the data in that it will not be possible to perform effective hypotheses testing, quality improvement analyses and population management without access to the full data set. No experimental intervention was involved. Patients underwent clinical assessments and receive standard of care as determined by the patients' physician.

**Data Availability Statement:** The data presented in this study are available in this article.

**Conflicts of Interest:** The authors declare no conflict of interest.

**Disclosures:** Precidiag—Consultant (C.J.M.); Receptor Life—Consultant (C.J.M.); Oxford University Press—Royalties (C.J.M.); Springer Publishing—Royalties/Editorial Role (C.J.M.).
