{"doi":"10.4088/jcp.22m14629","title":"Effects of Vitamin D<sub>3</sub> and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults","abstract":"Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 í 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011–March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 ). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9. Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 ; omega-3s vs placebo: 1.08 ). There were no significant differences in PHQ-9 score change comparing either supplement with placebo. Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696435 J Clin Psychiatry 2023;84(4):22m14629 Author affiliations are listed at the end of this article.","journal":"The Journal of Clinical Psychiatry","year":2023,"id":339870,"datarank":0.6451899517407552,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.22020795013232272,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.22020795013232272,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":15,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01696435"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320517,"name":"David Mischoulon","orcid":"0000-0001-7233-5860","position":1,"is_corresponding":false},{"id":323419,"name":"Grace Chang","orcid":"0000-0002-5508-3013","position":2,"is_corresponding":false},{"id":232625,"name":"Nancy R. Cook","orcid":"0000-0002-9705-0842","position":3,"is_corresponding":false},{"id":1074254,"name":"Alison Weinberg","orcid":null,"position":4,"is_corresponding":false},{"id":700003,"name":"Trisha Copeland","orcid":null,"position":5,"is_corresponding":false},{"id":6854,"name":"Jae H. Kang","orcid":"0000-0003-4812-0557","position":6,"is_corresponding":false},{"id":239408,"name":"Vadim Bubes","orcid":null,"position":7,"is_corresponding":false},{"id":754356,"name":"Georgina Friedenberg","orcid":null,"position":8,"is_corresponding":false},{"id":24985,"name":"Meryl S. LeBoff","orcid":"0000-0001-5797-4947","position":9,"is_corresponding":false},{"id":20423,"name":"I‐Min Lee","orcid":"0000-0002-1083-6907","position":10,"is_corresponding":false},{"id":6430,"name":"Julie E. Buring","orcid":"0000-0003-2648-8692","position":11,"is_corresponding":false},{"id":11268,"name":"JoAnn E. Manson","orcid":"0000-0002-9426-7595","position":12,"is_corresponding":false},{"id":303746,"name":"Charles F. Reynolds","orcid":"0000-0002-2605-7887","position":13,"is_corresponding":false},{"id":323420,"name":"Olivia I. Okereke","orcid":"0000-0002-9523-2693","position":14,"is_corresponding":false},{"id":323417,"name":"Chirag M. Vyas","orcid":"0000-0002-4262-2786","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37378490","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}