{"protocolSection":{"identificationModule":{"nctId":"NCT02960763","orgStudyIdInfo":{"id":"201609085"},"secondaryIdInfos":[{"id":"TRD-1511-33321","type":"OTHER_GRANT","domain":"PCORI"}],"organization":{"fullName":"Washington University School of Medicine","class":"OTHER"},"briefTitle":"Optimizing Outcomes of Treatment-Resistant Depression in Older Adults","officialTitle":"Optimizing Outcomes of Treatment-Resistant Depression in Older Adults","acronym":"OPTIMUM"},"statusModule":{"statusVerifiedDate":"2024-09","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2017-02-24","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2020-09-28","type":"ACTUAL"},"completionDateStruct":{"date":"2021-09-01","type":"ACTUAL"},"studyFirstSubmitDate":"2016-10-28","studyFirstSubmitQcDate":"2016-11-07","studyFirstPostDateStruct":{"date":"2016-11-10","type":"ESTIMATED"},"resultsFirstSubmitDate":"2022-02-01","resultsFirstSubmitQcDate":"2022-05-20","resultsFirstPostDateStruct":{"date":"2022-05-24","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-09-18","lastUpdatePostDateStruct":{"date":"2024-10-03","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Eric Lenze","investigatorTitle":"Professor of Psychiatry","investigatorAffiliation":"Washington University School of Medicine"},"leadSponsor":{"name":"Washington University School of Medicine","class":"OTHER"},"collaborators":[{"name":"Patient-Centered Outcomes Research Institute","class":"OTHER"},{"name":"National Institute of Mental Health (NIMH)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD).","detailedDescription":"Older adult participants with treatment-resistant depression will be randomly assigned to a Step 1 medication strategy.\n\n* Adding aripiprazole to current antidepressant medication\n* Adding bupropion to current antidepressant medication\n* Replacing current antidepressant medication with bupropion\n\nIf depression is not relieved at the end of 10 weeks, or if participants do not qualify for Step 1, participants will be randomly assigned to a Step 2 medication strategy:\n\n* Adding lithium to current antidepressant medication\n* Replacing current antidepressant medication with nortriptyline\n\nAll medication strategies will be offered in collaboration with participants' own physicians with the the research team providing support and guidance.\n\nAfter treatment in Step 1 and/or Step 2, participants will enter the Continuation Phase to assess long term follow-up outcomes for 12 months.\n\nParticipants in this clinical trial will also be asked to participate in an additional study to gather imaging and biomarker data."},"conditionsModule":{"conditions":["Treatment Resistant Depression","Major Depressive Disorder","Treatment-Refractory Depression","Late Life Depression","Geriatric Depression"],"keywords":["Comparative Effectiveness Research","Pragmatic Clinical Trials","Patient-Centered Outcomes Research"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"SINGLE","whoMasked":["OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":742,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Aripiprazole Augmentation","type":"EXPERIMENTAL","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.","interventionNames":["Drug: Aripiprazole Augmentation"]},{"label":"Bupropion Augmentation","type":"EXPERIMENTAL","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.","interventionNames":["Drug: Bupropion Augmentation"]},{"label":"Switch to Bupropion","type":"EXPERIMENTAL","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.","interventionNames":["Drug: Switch to bupropion"]},{"label":"Lithium Augmentation","type":"EXPERIMENTAL","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.","interventionNames":["Drug: Lithium Augmentation"]},{"label":"Switch to Nortriptyline","type":"EXPERIMENTAL","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.","interventionNames":["Drug: Switch to nortriptyline"]}],"interventions":[{"type":"DRUG","name":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects.","armGroupLabels":["Aripiprazole Augmentation"],"otherNames":["Abilify"]},{"type":"DRUG","name":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.","armGroupLabels":["Bupropion Augmentation"],"otherNames":["Wellbutrin"]},{"type":"DRUG","name":"Switch to bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.","armGroupLabels":["Switch to Bupropion"],"otherNames":["Wellbutrin"]},{"type":"DRUG","name":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.","armGroupLabels":["Lithium Augmentation"],"otherNames":["Lithium carbonate","Eskalith"]},{"type":"DRUG","name":"Switch to nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml","armGroupLabels":["Switch to Nortriptyline"],"otherNames":["Pamelor,"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Psychological Well-Being","description":"Psychological well-being was assessed using the NIH Toolbox Psychological Wellbeing subscales of Positive Affect and General Life Satisfaction, with a T score calculated as the average of these two subscales. Higher scores indicate greater positive affect and life satisfaction. Reference T-score (mean=50, SD=10).","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks"},{"measure":"Number of Participants With Remission From Depression","description":"Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms.","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks"},{"measure":"Serious Adverse Events","description":"Life threatening illness, hospitalization, or need of medical care.","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Men and women aged 60 and older\n* Current Major Depressive Disorder (MDD)\n* Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length\n* Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher\n\nExclusion Criteria:\n\n* Inability to provide informed consent\n* Dementia\n* Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms\n* High risk for suicide and unable to be managed safely in the clinical trial\n* Contraindication to proposed study medications, as determined by study physician including history of intolerance or non-response to proposed medications.\n* Non-correctable, clinically significant sensory impairment interfering with participation\n* Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.\n* Moderate to severe substance or alcohol use disorder","healthyVolunteers":false,"sex":"ALL","minimumAge":"60 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Eric Lenze, MD","affiliation":"Washington University School of Medicine","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"UCLA Late-Life Mood, Stress, and Wellness Research Program","city":"Los Angeles","state":"California","zip":"90095","country":"United States","geoPoint":{"lat":34.05223,"lon":-118.24368}},{"facility":"Washington University School of Medicine Healthy Mind Lab","city":"St Louis","state":"Missouri","zip":"63110","country":"United States","geoPoint":{"lat":38.62727,"lon":-90.19789}},{"facility":"Columbia University Adult and Late Life Depression Clinic","city":"New York","state":"New York","zip":"10032","country":"United States","geoPoint":{"lat":40.71427,"lon":-74.00597}},{"facility":"UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program","city":"Pittsburgh","state":"Pennsylvania","zip":"15213","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}},{"facility":"Centre for Addiction and Mental Health","city":"Toronto","state":"Ontario","zip":"M6J-1H4","country":"Canada","geoPoint":{"lat":43.70643,"lon":-79.39864}}]},"referencesModule":{"references":[{"pmid":"41237789","type":"DERIVED","citation":"Oughli HA, Ainsworth NJ, Butters MA, Brown PJ, Gebara MA, Gettinger TR, Karp JF, Lavretsky H, Lenard E, Miller JP, Mulsant BH, Nicol GE, Reynolds CF 3rd, Yingling M, Lenze EJ; OPTIMUM Research Group. Cognitive changes in older adults receiving pharmacotherapy for treatment-resistant depression: a secondary analysis of the OPTIMUM randomised controlled trial. Lancet Healthy Longev. 2025 Oct;6(10):100767. doi: 10.1016/j.lanhl.2025.100767. Epub 2025 Nov 11."},{"pmid":"38822571","type":"DERIVED","citation":"Srifuengfung M, Lenze EJ, Roose SP, Brown PJ, Lavretsky H, Karp JF, Reynolds CF 3rd, Yingling M, Sa-Nguanpanich N, Mulsant BH. Alcohol and substance use in older adults with treatment-resistant depression. Int J Geriatr Psychiatry. 2024 Jun;39(6):e6105. doi: 10.1002/gps.6105."},{"pmid":"36867173","type":"DERIVED","citation":"Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds CF 3rd, Blumberger DM, Brown PJ, Cristancho P, Flint AJ, Gebara MA, Gettinger TR, Lenard E, Miller JP, Nicol GE, Oughli HA, Pham VT, Rollman BL, Yang L, Karp JF. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. N Engl J Med. 2023 Mar 23;388(12):1067-1079. doi: 10.1056/NEJMoa2204462. Epub 2023 Mar 3."}]},"ipdSharingStatementModule":{"ipdSharing":"YES","description":"A cleaned, complete, and de-identified copy of the final data set including administrative and technical metadata records will be made available through a Washington University in St. Louis (WUSTL) secure repository and registered at clinicaltrials.gov."}},"resultsSection":{"participantFlowModule":{"recruitmentDetails":"Patients were recruited based on referrals from primary care providers (PCPs) or psychiatrists and self-referrals. This was further checked by using tools electronic medical records (EMRs) and using EMR-launched clinical decision tools. Print, radio, and social media advertising were used too. If patients self-referred, treatment recommendations were given by their community providers or a psychiatrist associated with the study.","groups":[{"id":"FG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects."},{"id":"FG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"FG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"FG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L."},{"id":"FG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml"}],"periods":[{"title":"Step 1","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"211"},{"groupId":"FG001","numSubjects":"206"},{"groupId":"FG002","numSubjects":"202"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"COMPLETED","comment":"\"Step 1\" only includes: Aripiprazole Augmentation Bupropion Augmentation Switch to Bupropion","achievements":[{"groupId":"FG000","numSubjects":"192"},{"groupId":"FG001","numSubjects":"188"},{"groupId":"FG002","numSubjects":"174"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"19"},{"groupId":"FG001","numSubjects":"18"},{"groupId":"FG002","numSubjects":"28"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"10"},{"groupId":"FG001","numSubjects":"8"},{"groupId":"FG002","numSubjects":"13"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"7"},{"groupId":"FG001","numSubjects":"9"},{"groupId":"FG002","numSubjects":"12"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Death","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"1"},{"groupId":"FG002","numSubjects":"1"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Investigator discretion","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"Other","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]}]},{"title":"Step 2","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"127"},{"groupId":"FG004","numSubjects":"121"}]},{"type":"People Who Participated in Step 1 and Continued to Participate in Step 2","achievements":[{"groupId":"FG000","numSubjects":"43"},{"groupId":"FG001","numSubjects":"44"},{"groupId":"FG002","numSubjects":"38"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"}]},{"type":"People Who Began Step 2 Without Having Participated in Step 1","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"63"},{"groupId":"FG004","numSubjects":"60"}]},{"type":"COMPLETED","comment":"\"Step 2\" only includes: Lithium Augmentation Switch to Nortriptyline","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"116"},{"groupId":"FG004","numSubjects":"116"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"11"},{"groupId":"FG004","numSubjects":"5"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"7"},{"groupId":"FG004","numSubjects":"3"}]},{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"4"},{"groupId":"FG004","numSubjects":"1"}]},{"type":"Investigator discretion","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"In Participant Flow, Step 2 \"milestones\" shows numbers recorded for those who switched from Step 1 to Step 2, and the numbers for those who started Step 2 without having first participated in Step 1.\n\n125 participants from the Step 1 arms (aripiprazole augmentation, bupropion augmentation, and switch to bupropion) also participated in Step 2.\n\nA grand total of 742 unique participants were randomized in the study.","groups":[{"id":"BG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects."},{"id":"BG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"BG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"BG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L."},{"id":"BG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml"},{"id":"BG005","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"867"}]}],"measures":[{"title":"Age, Continuous","description":"Age for Step 1 participants","populationDescription":"Step 1 had 619 participants enrolled","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"69.07","spread":"6.46"},{"groupId":"BG001","value":"69.13","spread":"7.14"},{"groupId":"BG002","value":"69.68","spread":"7.71"},{"groupId":"BG005","value":"69.29","spread":"7.10"}]}]}]},{"title":"Age, Customized","description":"Age of Step 2 participants","populationDescription":"Step 2 had 248 participants enrolled","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"69.04","spread":"6.00"},{"groupId":"BG004","value":"68.03","spread":"5.72"},{"groupId":"BG005","value":"68.55","spread":"5.88"}]}]}]},{"title":"Sex: Female, Male","description":"Step 1 participants","populationDescription":"Step 1 totals for sex of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"144"},{"groupId":"BG001","value":"142"},{"groupId":"BG002","value":"127"},{"groupId":"BG005","value":"413"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"67"},{"groupId":"BG001","value":"64"},{"groupId":"BG002","value":"75"},{"groupId":"BG005","value":"206"}]}]}]},{"title":"Sex: Female, Male","description":"Step 2 participants","populationDescription":"Step 2 sex of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"title":"Female","measurements":[{"groupId":"BG003","value":"90"},{"groupId":"BG004","value":"83"},{"groupId":"BG005","value":"173"}]},{"title":"Male","measurements":[{"groupId":"BG003","value":"37"},{"groupId":"BG004","value":"38"},{"groupId":"BG005","value":"75"}]}]}]},{"title":"Race/Ethnicity, Customized","description":"Step 1 participants","populationDescription":"Step 1 race/ethnicity of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"White","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"173"},{"groupId":"BG001","value":"174"},{"groupId":"BG002","value":"175"},{"groupId":"BG005","value":"522"}]}]},{"title":"African American","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"16"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"13"},{"groupId":"BG005","value":"46"}]}]},{"title":"Other","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"22"},{"groupId":"BG001","value":"15"},{"groupId":"BG002","value":"14"},{"groupId":"BG005","value":"51"}]}]}]},{"title":"Race/Ethnicity, Customized","description":"Step 1 participants","populationDescription":"Step 1 race/ethnicity of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"Hispanic/Latino","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"22"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"13"},{"groupId":"BG005","value":"52"}]}]},{"title":"Other","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"211"},{"groupId":"BG001","value":"206"},{"groupId":"BG002","value":"202"},{"groupId":"BG003","value":"0"},{"groupId":"BG004","value":"0"},{"groupId":"BG005","value":"619"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"189"},{"groupId":"BG001","value":"189"},{"groupId":"BG002","value":"189"},{"groupId":"BG005","value":"567"}]}]}]},{"title":"Race/Ethnicity, Customized","description":"Step 2 participants","populationDescription":"Step 2 race/ethnicity of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"White","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"116"},{"groupId":"BG004","value":"106"},{"groupId":"BG005","value":"222"}]}]},{"title":"African American","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"7"},{"groupId":"BG004","value":"4"},{"groupId":"BG005","value":"11"}]}]},{"title":"Other","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"4"},{"groupId":"BG004","value":"11"},{"groupId":"BG005","value":"15"}]}]}]},{"title":"Race/Ethnicity, Customized","description":"Step 2 participants","populationDescription":"Step 2 race/ethnicity of participants enrolled","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"Hispanic/Latino","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"3"},{"groupId":"BG004","value":"10"},{"groupId":"BG005","value":"13"}]}]},{"title":"Other","denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"127"},{"groupId":"BG004","value":"121"},{"groupId":"BG005","value":"248"}]}],"categories":[{"measurements":[{"groupId":"BG003","value":"124"},{"groupId":"BG004","value":"111"},{"groupId":"BG005","value":"235"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Psychological Well-Being","description":"Psychological well-being was assessed using the NIH Toolbox Psychological Wellbeing subscales of Positive Affect and General Life Satisfaction, with a T score calculated as the average of these two subscales. Higher scores indicate greater positive affect and life satisfaction. Reference T-score (mean=50, SD=10).","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"t-score","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks","groups":[{"id":"OG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects."},{"id":"OG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L."},{"id":"OG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"211"},{"groupId":"OG001","value":"206"},{"groupId":"OG002","value":"202"},{"groupId":"OG003","value":"127"},{"groupId":"OG004","value":"121"}]}],"classes":[{"title":"baseline","categories":[{"measurements":[{"groupId":"OG000","value":"34.7","lowerLimit":"33.8","upperLimit":"35.6"},{"groupId":"OG001","value":"35.0","lowerLimit":"34.1","upperLimit":"36.0"},{"groupId":"OG002","value":"34.8","lowerLimit":"33.8","upperLimit":"35.7"},{"groupId":"OG003","value":"33.1","lowerLimit":"31.9","upperLimit":"34.4"},{"groupId":"OG004","value":"34.2","lowerLimit":"32.9","upperLimit":"35.4"}]}]},{"title":"10 weeks","categories":[{"measurements":[{"groupId":"OG000","value":"38.8","lowerLimit":"37.9","upperLimit":"39.8"},{"groupId":"OG001","value":"38.7","lowerLimit":"37.8","upperLimit":"39.7"},{"groupId":"OG002","value":"36.1","lowerLimit":"35.1","upperLimit":"37.2"},{"groupId":"OG003","value":"35.7","lowerLimit":"34.4","upperLimit":"37.1"},{"groupId":"OG004","value":"35.6","lowerLimit":"34.3","upperLimit":"37.0"}]}]}],"analyses":[{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY","nonInferiorityComment":"Repeated measure of 2\\*2\\*3 ANOVA with age (60 - 70, \\> 70), time (baseline, end of Active phase of Step 1) by treatment group (3 levels). Tests were conducted with a Hochberg Step-down procedure. If the comparison with the lowest p-value \\< 0.05/3 it is significant. If the second lowest p-value is also \\< 0.05/2 then it also will be significant and if the third p-value is \\< 0.05 then it also will be significant.","pValue":"0.010","pValueComment":"Equivalence of group","statisticalMethod":"ANOVA"},{"groupIds":["OG000","OG002"],"nonInferiorityType":"SUPERIORITY","nonInferiorityComment":"Repeated measure of 2\\*2\\*3 ANOVA with age (60 - 70, \\> 70), time (baseline, end of Active phase of Step 1) by treatment group (3 levels). Tests were conducted with a Hochberg Step-down procedure. If the comparison with the lowest p-value \\< 0.05/3 it is significant. If the second lowest p-value is also \\< 0.05/2 then it also will be significant and if the third p-value is \\< 0.05 then it also will be significant.","pValue":"0.004","pValueComment":"augment with aripiprazole vs switch to bupropion","statisticalMethod":"ANOVA"},{"groupIds":["OG001","OG002"],"nonInferiorityType":"SUPERIORITY","nonInferiorityComment":"Repeated measure of 2\\*2\\*3 ANOVA with age (60 - 70, \\> 70), time (baseline, end of Active phase of Step 1) by treatment group (3 levels). Tests were conducted with a Hochberg Step-down procedure. If the comparison with the lowest p-value \\< 0.05/3 it is significant. If the second lowest p-value is also \\< 0.05/2 then it also will be significant and if the third p-value is \\< 0.05 then it also will be significant.","pValue":"0.017","pValueComment":"augment with bupropion vs switch to bupropion","statisticalMethod":"ANOVA"},{"groupIds":["OG000","OG001"],"groupDescription":"Repeated measure of 2\\*2\\*3 ANOVA with age (60 - 70, \\> 70), time (baseline, end of Active phase of Step 1) by treatment group (3 levels). Tests were conducted with a Hochberg Step-down procedure. If the comparison with the lowest p-value \\< 0.05/3 it is significant. If the second lowest p-value is also \\< 0.05/2 then it also will be significant and if the third p-value is \\< 0.05 then it also will be significant.","nonInferiorityType":"SUPERIORITY","pValue":"0.650","statisticalMethod":"ANOVA"},{"groupIds":["OG000","OG001","OG002"],"groupDescription":"Repeated measure of 2\\*2\\*3 ANOVA with age (60 - 70, \\> 70), time (baseline, end of Active phase of Step 1) by treatment group (3 levels). Tests were conducted with a Hochberg Step-down procedure. If the comparison with the lowest p-value \\< 0.05/3 it is significant. If the second lowest p-value is also \\< 0.05/2 then it also will be significant and if the third p-value is \\< 0.05 then it also will be significant.","nonInferiorityType":"SUPERIORITY","pValue":"0.003","pValueComment":"augmentation versus switch","statisticalMethod":"ANOVA"},{"groupIds":["OG003","OG004"],"nonInferiorityType":"SUPERIORITY","nonInferiorityComment":"For those who proceed to Step 2, analogous repeated measures 2\\*2\\*2 ANOVA will be used with a significance level of .05 for the time\\*treatment group comparison.","pValue":"0.385","statisticalMethod":"ANOVA"}]},{"type":"PRIMARY","title":"Number of Participants With Remission From Depression","description":"Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks","groups":[{"id":"OG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects."},{"id":"OG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L."},{"id":"OG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"211"},{"groupId":"OG001","value":"206"},{"groupId":"OG002","value":"202"},{"groupId":"OG003","value":"127"},{"groupId":"OG004","value":"121"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"61"},{"groupId":"OG001","value":"58"},{"groupId":"OG002","value":"39"},{"groupId":"OG003","value":"24"},{"groupId":"OG004","value":"26"}]}]}],"analyses":[{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.038","pValueComment":"Group effect","statisticalMethod":"generalized linear model with logistic l"},{"groupIds":["OG000","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.021","pValueComment":"augmentation with aripiprazole vs switch to bupropion","statisticalMethod":"generalized linear model with logistic l"},{"groupIds":["OG001","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.027","pValueComment":"augmentation with bupropion vs switch to bupropion","statisticalMethod":"generalized linear model with logistic l"},{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"0.934","pValueComment":"Augmentation with aripiprazole v augmentation with bupropion","statisticalMethod":"generalized linear model with logistic l"},{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.011","pValueComment":"augmentation versus switch","statisticalMethod":"generalized linear model with logistic l"},{"groupIds":["OG003","OG004"],"nonInferiorityType":"SUPERIORITY","pValue":"0.500","statisticalMethod":"generalized linear model with logistic l"}]},{"type":"PRIMARY","title":"Serious Adverse Events","description":"Life threatening illness, hospitalization, or need of medical care.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks","groups":[{"id":"OG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects."},{"id":"OG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects."},{"id":"OG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L."},{"id":"OG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"211"},{"groupId":"OG001","value":"206"},{"groupId":"OG002","value":"202"},{"groupId":"OG003","value":"127"},{"groupId":"OG004","value":"121"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"15"},{"groupId":"OG002","value":"19"},{"groupId":"OG003","value":"12"},{"groupId":"OG004","value":"11"}]}]}],"analyses":[{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.164","pValueComment":"Cox models time to event comparing treatment arms.","statisticalMethod":"Regression, Cox"},{"groupIds":["OG000","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.103","statisticalMethod":"Regression, Cox"},{"groupIds":["OG001","OG002"],"nonInferiorityType":"SUPERIORITY","pValue":"0.127","statisticalMethod":"Regression, Cox"},{"groupIds":["OG003","OG004"],"nonInferiorityType":"SUPERIORITY","pValue":"0.524","pValueComment":"Cox models to examine time to event comparing treatment arms.","statisticalMethod":"Regression, Cox"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Adverse event data were collected during phone assessments every other week during Step 1 and Step 2 (approximately 10 weeks each) for approximately 20 weeks of event data.","description":"This study assessed adverse events (in particular falls) to determine how safe and tolerable the treatments were. This was done because it is important for doctors to be able to cite safety concerns as one of the main restrictions in treatment of depression in older adults. One challenge with the rates of AE's/SAE's was because of the naturally high rate of medical problems and falls in depressed older adults. Most of the SAE's reported were decided to not be related to treatment.","eventGroups":[{"id":"EG000","title":"Aripiprazole Augmentation","description":"Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.\n\nAripiprazole Augmentation: Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects.","deathsNumAffected":1,"deathsNumAtRisk":211,"seriousNumAffected":15,"seriousNumAtRisk":211,"otherNumAffected":148,"otherNumAtRisk":211},{"id":"EG001","title":"Bupropion Augmentation","description":"Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nBupropion Augmentation: Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.","deathsNumAffected":1,"deathsNumAtRisk":206,"seriousNumAffected":15,"seriousNumAtRisk":206,"otherNumAffected":120,"otherNumAtRisk":206},{"id":"EG002","title":"Switch to Bupropion","description":"Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.\n\nSwitch to bupropion: Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.","deathsNumAffected":1,"deathsNumAtRisk":202,"seriousNumAffected":19,"seriousNumAtRisk":202,"otherNumAffected":136,"otherNumAtRisk":202},{"id":"EG003","title":"Lithium Augmentation","description":"Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.\n\nLithium Augmentation: Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.","deathsNumAffected":0,"deathsNumAtRisk":127,"seriousNumAffected":12,"seriousNumAtRisk":127,"otherNumAffected":93,"otherNumAtRisk":127},{"id":"EG004","title":"Switch to Nortriptyline","description":"Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.\n\nSwitch to nortriptyline: Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml","deathsNumAffected":0,"deathsNumAtRisk":121,"seriousNumAffected":11,"seriousNumAtRisk":121,"otherNumAffected":93,"otherNumAtRisk":121}],"seriousEvents":[{"term":"Psychiatric Hospitalization","organSystem":"Psychiatric disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":211},{"groupId":"EG001","numEvents":3,"numAffected":3,"numAtRisk":206},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":202},{"groupId":"EG003","numEvents":0,"numAffected":0,"numAtRisk":127},{"groupId":"EG004","numEvents":2,"numAffected":2,"numAtRisk":121}]},{"term":"Non-psychiatric Hospitalization","organSystem":"General 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disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":16,"numAtRisk":211},{"groupId":"EG001","numAffected":17,"numAtRisk":206},{"groupId":"EG002","numAffected":15,"numAtRisk":202},{"groupId":"EG003","numAffected":13,"numAtRisk":127},{"groupId":"EG004","numAffected":6,"numAtRisk":121}]},{"term":"Reduced Salivation","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","notes":"dryness of mouth","stats":[{"groupId":"EG000","numAffected":15,"numAtRisk":211},{"groupId":"EG001","numAffected":30,"numAtRisk":206},{"groupId":"EG002","numAffected":23,"numAtRisk":202},{"groupId":"EG003","numAffected":13,"numAtRisk":127},{"groupId":"EG004","numAffected":51,"numAtRisk":121}]},{"term":"Nausea/Vomiting","organSystem":"Gastrointestinal disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":15,"numAtRisk":211},{"groupId":"EG001","numAffected":25,"numAtRisk":206},{"groupId":"EG002","numAffected":31,"numAtRisk":202},{"groupId":"EG003","numAffected":12,"numAtRisk":127},{"groupId":"EG004","numAffected":9,"numAtRisk":121}]},{"term":"Diarrhea","organSystem":"Gastrointestinal disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":14,"numAtRisk":211},{"groupId":"EG001","numAffected":12,"numAtRisk":206},{"groupId":"EG002","numAffected":11,"numAtRisk":202},{"groupId":"EG003","numAffected":8,"numAtRisk":127},{"groupId":"EG004","numAffected":7,"numAtRisk":121}]},{"term":"Constipation","organSystem":"Gastrointestinal disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":15,"numAtRisk":211},{"groupId":"EG001","numAffected":20,"numAtRisk":206},{"groupId":"EG002","numAffected":18,"numAtRisk":202},{"groupId":"EG003","numAffected":6,"numAtRisk":127},{"groupId":"EG004","numAffected":20,"numAtRisk":121}]},{"term":"Weight gain","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":32,"numAtRisk":211},{"groupId":"EG001","numAffected":3,"numAtRisk":206},{"groupId":"EG002","numAffected":1,"numAtRisk":202},{"groupId":"EG003","numAffected":8,"numAtRisk":127},{"groupId":"EG004","numAffected":4,"numAtRisk":121}]},{"term":"Cold/Flu Symptoms","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":29,"numAtRisk":211},{"groupId":"EG001","numAffected":18,"numAtRisk":206},{"groupId":"EG002","numAffected":23,"numAtRisk":202},{"groupId":"EG003","numAffected":13,"numAtRisk":127},{"groupId":"EG004","numAffected":13,"numAtRisk":121}]},{"term":"Dizziness","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":36,"numAtRisk":211},{"groupId":"EG001","numAffected":41,"numAtRisk":206},{"groupId":"EG002","numAffected":40,"numAtRisk":202},{"groupId":"EG003","numAffected":28,"numAtRisk":127},{"groupId":"EG004","numAffected":21,"numAtRisk":121}]},{"term":"Fall","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":11,"numAtRisk":211},{"groupId":"EG001","numAffected":16,"numAtRisk":206},{"groupId":"EG002","numAffected":15,"numAtRisk":202},{"groupId":"EG003","numAffected":10,"numAtRisk":127},{"groupId":"EG004","numAffected":5,"numAtRisk":121}]},{"term":"Increased Appetite Without Weight Gain","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":23,"numAtRisk":211},{"groupId":"EG001","numAffected":2,"numAtRisk":206},{"groupId":"EG002","numAffected":6,"numAtRisk":202},{"groupId":"EG003","numAffected":2,"numAtRisk":127},{"groupId":"EG004","numAffected":6,"numAtRisk":121}]},{"term":"Irritability or Emotional Lability","organSystem":"Psychiatric disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":10,"numAtRisk":211},{"groupId":"EG001","numAffected":12,"numAtRisk":206},{"groupId":"EG002","numAffected":34,"numAtRisk":202},{"groupId":"EG003","numAffected":5,"numAtRisk":127},{"groupId":"EG004","numAffected":15,"numAtRisk":121}]},{"term":"Concenctration Difficulties","organSystem":"Psychiatric disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":11,"numAtRisk":211},{"groupId":"EG001","numAffected":4,"numAtRisk":206},{"groupId":"EG002","numAffected":10,"numAtRisk":202},{"groupId":"EG003","numAffected":9,"numAtRisk":127},{"groupId":"EG004","numAffected":10,"numAtRisk":121}]},{"term":"Asthenia/Lassitude/Increased Fatiguability","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":18,"numAtRisk":211},{"groupId":"EG001","numAffected":11,"numAtRisk":206},{"groupId":"EG002","numAffected":3,"numAtRisk":202},{"groupId":"EG003","numAffected":18,"numAtRisk":127},{"groupId":"EG004","numAffected":11,"numAtRisk":121}]},{"term":"Sleepiness/Sedation","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":20,"numAtRisk":211},{"groupId":"EG001","numAffected":9,"numAtRisk":206},{"groupId":"EG002","numAffected":3,"numAtRisk":202},{"groupId":"EG003","numAffected":11,"numAtRisk":127},{"groupId":"EG004","numAffected":12,"numAtRisk":121}]},{"term":"Tension/Inner Unrest","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":30,"numAtRisk":211},{"groupId":"EG001","numAffected":20,"numAtRisk":206},{"groupId":"EG002","numAffected":29,"numAtRisk":202},{"groupId":"EG003","numAffected":8,"numAtRisk":127},{"groupId":"EG004","numAffected":9,"numAtRisk":121}]},{"term":"Tremor","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":14,"numAtRisk":211},{"groupId":"EG001","numAffected":20,"numAtRisk":206},{"groupId":"EG002","numAffected":13,"numAtRisk":202},{"groupId":"EG003","numAffected":34,"numAtRisk":127},{"groupId":"EG004","numAffected":4,"numAtRisk":121}]},{"term":"Polyuria/Polydipsia","organSystem":"Renal and urinary disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","notes":"frequent need to urinate/feeling of extreme 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