{"protocolSection":{"identificationModule":{"nctId":"NCT00177671","orgStudyIdInfo":{"id":"R01MH043832-03","type":"NIH","link":"https://reporter.nih.gov/quickSearch/R01MH043832-03"},"secondaryIdInfos":[{"id":"R01MH043832","type":"NIH","link":"https://reporter.nih.gov/quickSearch/R01MH043832"},{"id":"0312018"},{"id":"DATR A4-GPS"}],"organization":{"fullName":"University of Pittsburgh","class":"OTHER"},"briefTitle":"Antidepressant Medication Plus Donepezil for Treating Late-life Depression","officialTitle":"Maintenance Therapies in Late-Life Depression: MTLD III"},"statusModule":{"statusVerifiedDate":"2013-01","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2003-12"},"primaryCompletionDateStruct":{"date":"2009-09","type":"ACTUAL"},"completionDateStruct":{"date":"2009-09","type":"ACTUAL"},"studyFirstSubmitDate":"2005-09-13","studyFirstSubmitQcDate":"2005-09-13","studyFirstPostDateStruct":{"date":"2005-09-15","type":"ESTIMATED"},"resultsFirstSubmitDate":"2011-02-18","resultsFirstSubmitQcDate":"2011-05-06","resultsFirstPostDateStruct":{"date":"2011-06-08","type":"ESTIMATED"},"lastUpdateSubmitDate":"2013-01-31","lastUpdatePostDateStruct":{"date":"2013-02-06","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"University of Pittsburgh","class":"OTHER"},"collaborators":[{"name":"National Institute of Mental Health (NIMH)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"This study will determine the effectiveness of combining escitalopram, venlafaxine, or duloxetine with donepezil, a medication used in Alzheimer's disease, in improving memory, concentration, attention, and problem solving abilities, and reducing the risk of depressive relapse in older individuals with depression.","detailedDescription":"The purpose of this research study is to learn if combining an antidepressant medication (escitalopram, venlafaxine, or duloxetine) with a medication used in Alzheimer's Disease (donepezil), in elderly patients age 65 and older with major depression, will help to 1) improve and/or maintain memory, concentration, attention, and problem solving abilities such as ability to balance a checkbook, pay bills, use the telephone, and 2) reduce the risk of depressive symptoms from returning. Study participation will last up to two years.\n\nWe aim to investigate pharmacologic strategies for improving and stabilizing cognitive functioning in late-life depression and minimizing progression of cognitive and associated functional impairment. Cognitive impairment in late-life depression has not been adequately addressed in previous intervention research, is a core feature of the illness, contributes markedly to disability and impaired quality of life, and is an overlooked but potentially critical target of intervention. Data from the MTLD II study suggest that treating depression does not normalize cognitive functions and may not prevent their progression. We will test a pharmacologic strategy involving the cholinesterase inhibitor donepezil, in combination with maintenance antidepressant pharmacotherapy (escitalopram, venlafaxine, or duloxetine), to improve and to maintain cognitive functioning and functional competence in elderly patients with major depression.\n\nWe hypothesize that maintenance antidepressant pharmacotherapy combined with donepezil will be superior to maintenance antidepressant pharmacotherapy combined with placebo/clinical management in (1) improving cognitive performance; and (2) slowing progression of cognitive impairment and decline in functional competence. We plan to recruit 200 patients aged 65 and above in current episodes of major depression. Those who respond to antidepressant pharmacotherapy with citalopram, venlafaxine, or duloxetine will then be randomly assigned on a double-blind basis to one of two 24-month treatments: 1)antidepressant pharmacotherapy plus donepezil/clinical management; or 2)antidepressant pharmacotherapy plus placebo/clinical management.\n\nFor information on related studies, please follow these links:\n\nhttp://clinicaltrials.gov/show/NCT00000377\n\nhttp://clinicaltrials.gov/show/NCT00178100"},"conditionsModule":{"conditions":["Depression","Dementia"],"keywords":["Depression","Dementia","Alzheimer's Disease","Cognitive","Donepezil","Memory","Function","Elderly","Late-Life"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":220,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"1","type":"EXPERIMENTAL","description":"escitalopram plus donepezil (DNP)in the experimental maintenance phase of the study.\n\nFor subjects failing to respond to escitalopram during the initial open phase of acute treatment we allowed the use of duloxetine or venlafaxine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation donepezil.\n\nParticipants remained on the same antidepressant medication and dosage throughout the 2 year maintenance phase of the study. In the event of a recurrence of major depression during maintenance treatment, dosages of antidepressant medication were raised, or the antidepressant was switched to venlafaxine or duloxetine.\n\nFor subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of duloxetine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.","interventionNames":["Drug: Escitalopram","Drug: Donepezil","Drug: Venlafaxine","Drug: Duloxetine"]},{"label":"2","type":"PLACEBO_COMPARATOR","description":"escitalopram plus placebo (PBO) in the experimental maintenance phase of the study.\n\nFor subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of duloxetine or venlafaxine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.\n\nParticipants remained on the same antidepressant medication and dosage throughout the 2 year maintenance phase of the study. In the event of a recurrence of major depression during maintenance treatment, dosages of antidepressant medication were raised, or the antidepressant was switched to venlafaxine or duloxetine.\n\nFor subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of venlafaxine or duloxetine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.","interventionNames":["Drug: Escitalopram","Drug: Venlafaxine","Drug: Placebo","Drug: Duloxetine"]}],"interventions":[{"type":"DRUG","name":"Escitalopram","description":"Escitalopram, 10mg to 20mg daily.","armGroupLabels":["1","2"],"otherNames":["Lexapro"]},{"type":"DRUG","name":"Donepezil","description":"Donepezil, 5mg to 10mg daily.","armGroupLabels":["1"],"otherNames":["aricept"]},{"type":"DRUG","name":"Venlafaxine","description":"Venlafaxine, 150mg to 300mg daily.","armGroupLabels":["1","2"],"otherNames":["effexor XR"]},{"type":"DRUG","name":"Placebo","armGroupLabels":["2"]},{"type":"DRUG","name":"Duloxetine","armGroupLabels":["1","2"],"otherNames":["cymbalta"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Global Cognitive Performance","description":"Cognitive performance was assessed with 17 well established and validated individual tests measuring multiple domains. We transformed raw scores for individual tests into Z-scores using the baseline distribution of a non-depressed, cognitively normal, older adult comparison group (N=36)of similar age, education, and medical health recruited concurrently with the depressed participants. These Z-scores were averaged within each neuropsychological area to produce domain scores and then averaged over all 17 tests to calculate a global cognition performance score.","timeFrame":"Measured at baseline and Years 1 and 2 in maintenance"},{"measure":"Cognitive Instrumental Activities of Daily Living (IADL)","description":"The PASS (a performance-based assessment of instrumental activities of daily living)generates a composite measure of 13 cognitive IADL items capturing performance on activities such as shopping, bill paying, medication management, and home safety. We report the percentage of subjects at each assessment point adjudged to have independent functioning. This was determined by a clinician rater observing subjects perform each task and rating them according to predetermined criteria on a 4 point scale, ranging from 0 (unable) to 3 (independent).","timeFrame":"baseline, year 1 and year 2"},{"measure":"Number of Participants With Recurrence of Major Depression","description":"Recurrence of major depressive episodes as determined by SCID/DSM IV: two weeks of low mood and/or anhedonia, together with at least five of the following symptoms: suicidal ideation, low energy, sleep disturbance, appetite disturbance, psychic anxiety or somatic anxiety. In addition, a diagnosis of major depression requires evidence of distress or impairment.","timeFrame":"2 years"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Current episode of major depression\n* HRS-D 17-item score of 15 or higher\n* Must be able to speak English\n* Willing to discontinue other psychotropics\n* Availability of family member/caregiver\n* Hearing capacity adequate to respond to raised conversational voice\n* Must have no formal diagnosis of dementia\n\nExclusion Criteria:\n\n* Meets DSM-IV criteria for bipolar disorder, schizophrenia, schizoaffective disorder, or a psychotic disorders\n* Alcohol/drug abuse within 12 months of study entry\n* History of treatment non-adherence in other clinic protocols\n* History of non-response to citalopram in other clinic protocols\n* History of non-tolerance to SSRI therapy","healthyVolunteers":true,"sex":"ALL","minimumAge":"65 Years","stdAges":["OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Bruce G. Pollock, MD, PhD","affiliation":"University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"University of Pittsburgh Medical Center","city":"Pittsburgh","state":"Pennsylvania","zip":"15213","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}}]},"referencesModule":{"references":[{"pmid":"21199965","type":"BACKGROUND","citation":"Reynolds CF 3rd, Butters MA, Lopez O, Pollock BG, Dew MA, Mulsant BH, Lenze EJ, Holm M, Rogers JC, Mazumdar S, Houck PR, Begley A, Anderson S, Karp JF, Miller MD, Whyte EM, Stack J, Gildengers A, Szanto K, Bensasi S, Kaufer DI, Kamboh MI, DeKosky ST. Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Arch Gen Psychiatry. 2011 Jan;68(1):51-60. doi: 10.1001/archgenpsychiatry.2010.184."},{"pmid":"24290367","type":"DERIVED","citation":"Diniz BS, Reynolds CF 3rd, Begley A, Dew MA, Anderson SJ, Lotrich F, Erickson KI, Lopez O, Aizenstein H, Sibille EL, Butters MA. Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. J Psychiatr Res. 2014 Feb;49:96-101. doi: 10.1016/j.jpsychires.2013.11.004. Epub 2013 Nov 20."},{"pmid":"24144505","type":"DERIVED","citation":"Andreescu C, Tudorascu DL, Butters MA, Tamburo E, Patel M, Price J, Karp JF, Reynolds CF 3rd, Aizenstein H. Resting state functional connectivity and treatment response in late-life depression. Psychiatry Res. 2013 Dec 30;214(3):313-21. doi: 10.1016/j.pscychresns.2013.08.007. Epub 2013 Oct 18."},{"pmid":"19210951","type":"DERIVED","citation":"Sheffrin M, Driscoll HC, Lenze EJ, Mulsant BH, Pollock BG, Miller MD, Butters MA, Dew MA, Reynolds CF 3rd. Pilot study of augmentation with aripiprazole for incomplete response in late-life depression: getting to remission. J Clin Psychiatry. 2009 Feb;70(2):208-13. doi: 10.4088/jcp.07m03805. Epub 2009 Feb 10."},{"pmid":"18251622","type":"DERIVED","citation":"Karp JF, Whyte EM, Lenze EJ, Dew MA, Begley A, Miller MD, Reynolds CF 3rd. Rescue pharmacotherapy with duloxetine for selective serotonin reuptake inhibitor nonresponders in late-life depression: outcome and tolerability. J Clin Psychiatry. 2008 Mar;69(3):457-63. doi: 10.4088/jcp.v69n0317."}]}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"28 enrolled participants were not randomized due to the following reasons: dementia (19), consent withdrawal (4), con-compliance with research procedures (3), supervening medical problems that precluded participation (2).","recruitmentDetails":"220 signed consent; 158 participants completed pre-randomization testing; 130 participants were randomized. Of these 130, 67 randomized to donepezil augmentation and 63 to placebo.","groups":[{"id":"FG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"FG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"67"},{"groupId":"FG001","numSubjects":"63"}]},{"type":"Month 12","achievements":[{"groupId":"FG000","numSubjects":"45"},{"groupId":"FG001","numSubjects":"57"}]},{"type":"Month 24","achievements":[{"groupId":"FG000","numSubjects":"42"},{"groupId":"FG001","numSubjects":"49"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"42"},{"groupId":"FG001","numSubjects":"49"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"25"},{"groupId":"FG001","numSubjects":"14"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"5"},{"groupId":"FG001","numSubjects":"6"}]},{"type":"medical complications","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"6"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Physician Decision","reasons":[{"groupId":"FG000","numSubjects":"12"},{"groupId":"FG001","numSubjects":"8"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"BG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"67"},{"groupId":"BG001","value":"63"},{"groupId":"BG002","value":"130"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"67"},{"groupId":"BG001","value":"63"},{"groupId":"BG002","value":"130"}]}]}]},{"title":"Age Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"73.1","spread":"6.5"},{"groupId":"BG001","value":"73.9","spread":"5.8"},{"groupId":"BG002","value":"73.5","spread":"6.2"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"49"},{"groupId":"BG001","value":"51"},{"groupId":"BG002","value":"100"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"18"},{"groupId":"BG001","value":"12"},{"groupId":"BG002","value":"30"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"67"},{"groupId":"BG001","value":"63"},{"groupId":"BG002","value":"130"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Global Cognitive Performance","description":"Cognitive performance was assessed with 17 well established and validated individual tests measuring multiple domains. We transformed raw scores for individual tests into Z-scores using the baseline distribution of a non-depressed, cognitively normal, older adult comparison group (N=36)of similar age, education, and medical health recruited concurrently with the depressed participants. These Z-scores were averaged within each neuropsychological area to produce domain scores and then averaged over all 17 tests to calculate a global cognition performance score.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"Z-score","timeFrame":"Measured at baseline and Years 1 and 2 in maintenance","groups":[{"id":"OG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"OG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"67"},{"groupId":"OG001","value":"63"}]}],"classes":[{"title":"Baseline (N=67;N=63)","categories":[{"measurements":[{"groupId":"OG000","value":"-0.47","spread":"0.88"},{"groupId":"OG001","value":"-0.47","spread":"0.76"}]}]},{"title":"Year 1 (N=45; N=57)","categories":[{"measurements":[{"groupId":"OG000","value":"-0.23","spread":"0.79"},{"groupId":"OG001","value":"-0.65","spread":"0.81"}]}]},{"title":"Year 2 N=42; N=49)","categories":[{"measurements":[{"groupId":"OG000","value":"-0.31","spread":"0.92"},{"groupId":"OG001","value":"-0.56","spread":"0.90"}]}]}]},{"type":"PRIMARY","title":"Cognitive Instrumental Activities of Daily Living (IADL)","description":"The PASS (a performance-based assessment of instrumental activities of daily living)generates a composite measure of 13 cognitive IADL items capturing performance on activities such as shopping, bill paying, medication management, and home safety. We report the percentage of subjects at each assessment point adjudged to have independent functioning. This was determined by a clinician rater observing subjects perform each task and rating them according to predetermined criteria on a 4 point scale, ranging from 0 (unable) to 3 (independent).","populationDescription":"Some participants refused this testing.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Percentage of participants","timeFrame":"baseline, year 1 and year 2","groups":[{"id":"OG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"OG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"33"},{"groupId":"OG001","value":"34"}]}],"classes":[{"title":"Baseline (N=33; N=34)","categories":[{"measurements":[{"groupId":"OG000","value":"54.10"},{"groupId":"OG001","value":"61.82"}]}]},{"title":"Year 1 (N=23; N=25)","categories":[{"measurements":[{"groupId":"OG000","value":"62.16"},{"groupId":"OG001","value":"54.35"}]}]},{"title":"Year 2 (N=11; N=17)","categories":[{"measurements":[{"groupId":"OG000","value":"36.67"},{"groupId":"OG001","value":"47.22"}]}]}]},{"type":"PRIMARY","title":"Number of Participants With Recurrence of Major Depression","description":"Recurrence of major depressive episodes as determined by SCID/DSM IV: two weeks of low mood and/or anhedonia, together with at least five of the following symptoms: suicidal ideation, low energy, sleep disturbance, appetite disturbance, psychic anxiety or somatic anxiety. In addition, a diagnosis of major depression requires evidence of distress or impairment.","reportingStatus":"POSTED","paramType":"NUMBER","dispersionType":"95% Confidence Interval","unitOfMeasure":"participants","timeFrame":"2 years","groups":[{"id":"OG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"OG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"67"},{"groupId":"OG001","value":"63"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"19","lowerLimit":"16","upperLimit":"31"},{"groupId":"OG001","value":"11","lowerLimit":"6","upperLimit":"18"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"We followed the intention to treat principle. We used Kaplan-Meier curves to quantify the percentage of participants who were free of depression recurrence over time. Cox proportional hazard models quantified hazard ratios comparing the 2 treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":".05","statisticalMethod":"Log Rank","paramType":"Hazard Ratio (HR)","paramValue":"3.97","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.00","ciUpperLimit":"4.41","dispersionType":"STANDARD_DEVIATION","dispersionValue":"2.09"}]},{"type":"POST_HOC","title":"Percentage of Participants With Mild Cognitive Impairment Converting to Dementia.","description":"Conversion to dementia was ascertained by the University of Pittsburgh Alzheimer Disease Research Center (ADRC), using data on neuropsychological performance and IADL functioning, as well as other relevant clinical data. Diagnoses were made according to National Alzheimer Coordinating Center criteria.","populationDescription":"This is the percent of participants with mild cognitive impairment (MCI) in each arm of the study.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Percent of Participants","timeFrame":"2 year","groups":[{"id":"OG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)"},{"id":"OG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"30"},{"groupId":"OG001","value":"27"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"33"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"2 years","description":"We determined adverse events by structured clinical interview.","eventGroups":[{"id":"EG000","title":"Donepezil","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)","seriousNumAffected":3,"seriousNumAtRisk":67,"otherNumAffected":0,"otherNumAtRisk":67},{"id":"EG001","title":"Placebo","description":"Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo","seriousNumAffected":1,"seriousNumAtRisk":63,"otherNumAffected":0,"otherNumAtRisk":63}],"seriousEvents":[{"term":"Suicide Attempt","organSystem":"Psychiatric disorders","sourceVocabulary":"standard terminology","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":67},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":63}]},{"term":"stroke","organSystem":"Nervous system disorders","sourceVocabulary":"standard terminology","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":67},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":63}]},{"term":"Myocardial infarcation with congestive heart failure","organSystem":"Cardiac disorders","sourceVocabulary":"standard terminology","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":67},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":63}]},{"term":"Death due to heart attack in person with history of coronary heart disease and hypertension.","organSystem":"Cardiac disorders","sourceVocabulary":"standard terminology","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":67},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":63}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Observations about dementia conversion rates were obtained from post hoc subgroup analyses of participants with mild cognitive impairment (N=57) and participants with normal cognition at time of randomization (N=63)."},"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Charles F. Reynolds III, MD","organization":"University of Pittsburgh","email":"reynoldscf@upmc.edu","phone":"412-246-6414"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D003863","term":"Depression"},{"id":"D003704","term":"Dementia"},{"id":"D000544","term":"Alzheimer Disease"}],"ancestors":[{"id":"D001526","term":"Behavioral Symptoms"},{"id":"D001519","term":"Behavior"},{"id":"D001927","term":"Brain Diseases"},{"id":"D002493","term":"Central Nervous System Diseases"},{"id":"D009422","term":"Nervous System Diseases"},{"id":"D019965","term":"Neurocognitive Disorders"},{"id":"D001523","term":"Mental Disorders"},{"id":"D024801","term":"Tauopathies"},{"id":"D019636","term":"Neurodegenerative Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D000089983","term":"Escitalopram"},{"id":"D000077265","term":"Donepezil"},{"id":"D000069470","term":"Venlafaxine Hydrochloride"},{"id":"D000068736","term":"Duloxetine Hydrochloride"}],"ancestors":[{"id":"D011437","term":"Propylamines"},{"id":"D000588","term":"Amines"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D009570","term":"Nitriles"},{"id":"D001572","term":"Benzofurans"},{"id":"D006574","term":"Heterocyclic Compounds, 2-Ring"},{"id":"D000072471","term":"Heterocyclic Compounds, Fused-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"},{"id":"D007189","term":"Indans"},{"id":"D007192","term":"Indenes"},{"id":"D011084","term":"Polycyclic Aromatic Hydrocarbons"},{"id":"D006841","term":"Hydrocarbons, Aromatic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"},{"id":"D010880","term":"Piperidines"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"},{"id":"D011083","term":"Polycyclic Compounds"},{"id":"D003511","term":"Cyclohexanols"},{"id":"D000441","term":"Hexanols"},{"id":"D005233","term":"Fatty Alcohols"},{"id":"D000438","term":"Alcohols"},{"id":"D010627","term":"Phenethylamines"},{"id":"D005021","term":"Ethylamines"},{"id":"D003510","term":"Cyclohexanes"},{"id":"D003516","term":"Cycloparaffins"},{"id":"D006840","term":"Hydrocarbons, Alicyclic"},{"id":"D008055","term":"Lipids"},{"id":"D013876","term":"Thiophenes"},{"id":"D013457","term":"Sulfur Compounds"}]}},"hasResults":true}