{"doi":"10.1056/nejmoa2204462","title":"Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression","abstract":"BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).","journal":"New England Journal of Medicine","year":2023,"id":317355,"datarank":1.9732195103111079,"base_score":4.382026634673881,"endowment":4.382026634673881,"self_citation_contribution":0.6573039952010823,"citation_network_contribution":1.3159155151100255,"self_endowment_contribution":0.6573039952010823,"citer_contribution":1.3159155151100255,"corpus_percentile":null,"corpus_rank":null,"citation_count":79,"citer_count":56,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02960763"]},"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":226870,"name":"Benoit H. Mulsant","orcid":"0000-0002-0303-6450","position":1,"is_corresponding":false},{"id":303477,"name":"Steven P. Roose","orcid":null,"position":2,"is_corresponding":false},{"id":303747,"name":"Helen Lavretsky","orcid":"0000-0001-9990-5085","position":3,"is_corresponding":false},{"id":303746,"name":"Charles F. Reynolds","orcid":"0000-0002-2605-7887","position":4,"is_corresponding":false},{"id":333475,"name":"Daniel M. Blumberger","orcid":"0000-0002-8422-5818","position":5,"is_corresponding":false},{"id":302339,"name":"Patrick J. Brown","orcid":"0000-0003-3906-6667","position":6,"is_corresponding":false},{"id":1022699,"name":"Pilar Cristancho","orcid":"0000-0003-0661-5607","position":7,"is_corresponding":false},{"id":3107,"name":"Alastair J. Flint","orcid":"0000-0001-6806-0235","position":8,"is_corresponding":false},{"id":818169,"name":"Marie Anne Gebara","orcid":"0000-0002-1711-3306","position":9,"is_corresponding":false},{"id":966564,"name":"Torie R Gettinger","orcid":"0000-0001-5606-0174","position":10,"is_corresponding":false},{"id":1023489,"name":"Emily Lenard","orcid":null,"position":11,"is_corresponding":false},{"id":12016,"name":"J. Philip Miller","orcid":"0000-0003-4568-6846","position":12,"is_corresponding":false},{"id":253970,"name":"Ginger E. Nicol","orcid":"0000-0001-5823-6129","position":13,"is_corresponding":false},{"id":686772,"name":"Hanadi Ajam Oughli","orcid":"0000-0002-9301-7412","position":14,"is_corresponding":false},{"id":1022700,"name":"Vy Pham","orcid":"0000-0003-2305-7096","position":15,"is_corresponding":false},{"id":732294,"name":"Bruce L. Rollman","orcid":"0000-0002-2937-7464","position":16,"is_corresponding":false},{"id":1022701,"name":"Lei Yang","orcid":"0000-0002-0655-8123","position":17,"is_corresponding":false},{"id":700918,"name":"Jordan F. Karp","orcid":"0000-0002-5171-5028","position":18,"is_corresponding":false},{"id":253971,"name":"Eric J. Lenze","orcid":"0000-0002-0471-9368","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:06:50.336418Z","pmid":"36867173","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":[]}