{"protocolSection":{"identificationModule":{"nctId":"NCT00892047","orgStudyIdInfo":{"id":"MH083660-01A1"},"organization":{"fullName":"University of Pittsburgh","class":"OTHER"},"briefTitle":"Incomplete Response in Late Life Depression: Getting to Remission (IRL GREY)","officialTitle":"Incomplete Response in Late Life Depression: Getting to Remission","acronym":"IRL GREY"},"statusModule":{"statusVerifiedDate":"2015-12","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2009-08"},"primaryCompletionDateStruct":{"date":"2014-09","type":"ACTUAL"},"completionDateStruct":{"date":"2014-09","type":"ACTUAL"},"studyFirstSubmitDate":"2009-04-29","studyFirstSubmitQcDate":"2009-05-01","studyFirstPostDateStruct":{"date":"2009-05-04","type":"ESTIMATED"},"resultsFirstSubmitDate":"2015-12-16","resultsFirstSubmitQcDate":"2015-12-16","resultsFirstPostDateStruct":{"date":"2015-12-17","type":"ESTIMATED"},"lastUpdateSubmitDate":"2015-12-16","lastUpdatePostDateStruct":{"date":"2015-12-17","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Charles Reynolds","investigatorTitle":"Director NIMH Center of Excellence in the Prevention and Treatment of Depression in Older Adults; UPMC Endowed Professor in Geriatric Psychiatry","investigatorAffiliation":"University of Pittsburgh"},"leadSponsor":{"name":"University of Pittsburgh","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"The primary aims of this study are to:\n\n1. Assess the efficacy of aripiprazole augmentation for the acute and continuation treatment of TRLLD.\n\n   Hypothesis 1: Patients with TRLLD (defined as those who do not remit after 12 weeks of acute treatment with venlafaxine XR) will have a higher rate of remission with aripiprazole than with placebo augmentation (primary outcome) and greater improvement in depressive symptoms and stability of remission (secondary outcomes).\n2. Assess the tolerability of aripiprazole in TRLLD with a focus on adiposity and akathisia/restlessness.\n\nHypothesis 2: Aripiprazole will be associated with a higher rate of clinically significant akathisia and increased adiposity than placebo.\n\nThe Secondary/exploratory aims of this study are to:\n\n1. Examine anxiety, medical burden, and executive impairment as moderators of aripiprazole augmentation efficacy in TRLLD.\n\n   Hypothesis 3: Pre-levels of anxiety symptoms, medical burden, and executive impairment will be treatment-specific factors: they will moderate the efficacy of aripiprazole augmentation. The aripiprazole-placebo difference will be greater in individuals with these variables, compared to those without these variables because these three factors will be associated with a decreased likelihood that \"staying the course\" with venlafaxine monotherapy will achieve remission.\n2. Examine genetic predictors (phase 1) and moderators (phase 2-3) of treatment outcomes, while controlling for drug exposure.\n\nHypothesis 4: Selected polymorphisms will reduce remission rate with venlafaxine and will reduce efficacy and tolerability with aripiprazole.","detailedDescription":"Incomplete response in the treatment of late-life depression (LLD) is a large public health challenge: at least 50% of older people fail to respond adequately to antidepressant pharmacotherapy, even under optimal treatment conditions. Treatment resistant late-life depression (TRLLD) increases risk for early relapse, undermines adherence to treatment for coexisting medical disorders, amplifies disability and cognitive impairment, imposes greater burden on family caregivers, and increases the risk for early mortality, including suicide. Getting to and sustaining remission is the primary goal of treatment, yet there is a paucity of controlled studies of how best to manage TRLLD.\n\nThis is a multi-site study being conducted by 3 sites: University of Pittsburgh, University of Toronto, and Washington University. We propose to enroll 500 subjects aged 60 and older with major depressive disorder at this site and treat them openly for 12 weeks with venlafaxine XR (up to 300mg/d) (phase 1). Participants meeting criteria for incomplete response will be randomly assigned to receive either aripiprazole (2-15 mg/d; target dose: 10 mg/d) or placebo augmentation (adding a pill without active medicine) of venlafaxine for 12 weeks (phase 2), with the goal of achieving remission (MADRS≤10 for two consecutive assessments). Those who remit in phase 2 will receive continuation treatment, with the same double-blinded intervention to which they were randomly assigned (phase 3), for 12 weeks to determine the stability of remission. Efficacy and tolerability data will provide a clinically informative estimate of benefits and risks of aripiprazole augmentation for TRLLD.\n\nIn addition to the primary goal of assessing these benefits and risks, we will develop evidence relevant to personalized treatment for LLD by testing the roles of clinical (comorbid anxiety, medical burden, and executive impairment) and genetic (selected polymorphisms in serotonin, norepinephrine, and dopamine genes) variables, while controlling for variability in drug exposure for efficacy and tolerability analyses. This approach will allow us to distinguish treatment-specific resistance factors versus general prognostic factors."},"conditionsModule":{"conditions":["Depression"],"keywords":["Depression","Aripiprazole","Venlafaxine","Partial Remission","Augmentation strategy","Treatment resistance","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":468,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"1: venlafaxine plus aripiprazole","type":"EXPERIMENTAL","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo","interventionNames":["Drug: venlafaxine XR plus aripiprazole"]},{"label":"2: Placebo Comparator","type":"EXPERIMENTAL","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo","interventionNames":["Drug: venlafaxine plus placebo"]}],"interventions":[{"type":"DRUG","name":"venlafaxine XR plus aripiprazole","description":"Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks.","armGroupLabels":["1: venlafaxine plus aripiprazole"],"otherNames":["effexor XR, abilify"]},{"type":"DRUG","name":"venlafaxine plus placebo","description":"Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks.","armGroupLabels":["2: Placebo Comparator"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS)","description":"The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten item instrument assessing depression symptoms. Possible scores range from 0-60; higher scores indicate greater severity of depression. Remission defined as score of 10 or less based on the MADRS.","timeFrame":"12 weeks"},{"measure":"Akathisia","description":"Percentage of participants who developed clinically significant akathisia.","timeFrame":"12 weeks"},{"measure":"Weight","description":"Weight change in kilograms","timeFrame":"Baseline through12 weeks"},{"measure":"Parkinsonism","description":"Percentage of participants who develop signs of parkinsonism","timeFrame":"12weeks"}],"secondaryOutcomes":[{"measure":"Emergent Suicidal Ideation in Those With no Ideation at the Start of Treatment","description":"percentage of participants who reported suicidal ideation during treatment but not at baseline","timeFrame":"12 weeks"},{"measure":"QTc Prolongation on EKG (to Greater or Equal to 480 Msec)","description":"percentage of participants","timeFrame":"12 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Age \\> 60 years.\n2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV.\n3. MADRS ≥ 15.\n\nExclusion Criteria:\n\n1. Inability to provide informed consent.\n2. Depressive symptoms not severe enough (i.e., MADRS \\< 15) at the baseline assessments.\n3. Dementia based upon DSM-IV criteria as well as a Folstein MMSE score of less than 24. Patients screened out due to dementia will be referred to a memory clinic or to the UPMC Alzheimer's Disease Research Center for evaluation to clarify the presence or absence of a dementia.\n4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID. A recommendation for psychiatric referral will be made in these cases.\n5. Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.\n6. High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.\n7. Contraindication to venlafaxine XR or aripiprazole as determined by study physician including history of intolerance of either venlafaxine XR or aripiprazole in the study target dosage range (venlafaxine XR at up to 225 mg/day; aripiprazole at up to 15mg/day).\n8. Failure to respond to at least 6 weeks of venlafaxine (\\>225 mg/d) plus aripiprazole (\\>10 mg/d).\n9. Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).\n10. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)\n11. Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician's and study physician clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases.\n12. Subjects taking psychotropic medications that cannot be safely tapered or discontinued prior to study initiation: this would include patients on Monoamine Oxidase Inhibitors (MAOI) who would need to be off the MAOI for 14 days to be eligible for the study to avoid adverse drug interactions. Patients will not be allowed to take antidepressant or atypical antipsychotic medication other than the study medication, unless it is a low dose antidepressant prescribed for chronic pain that would not be medically advisable to stop (e.g., amitryptyline 50mg). If a patient's depression is adequately treated on his/her psychotropic medication, he/she would not be eligible for the study. If a patient failed a trial of venlafaxine (12 weeks of treatment with venlafaxine including at least 6 weeks on 300mg/day), he/she would not be eligible. The following are allowed: benzodiazepines up to 2mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy). Except for MAOIs, there is really no clinical rationale to exclude patients on specific concomitant medications unless they are medically unstable (in which case they are excluded from participation). As noted, patients on an MAOI would need to be off the MAOI for 14 days to protect from adverse drug interactions.","healthyVolunteers":false,"sex":"ALL","minimumAge":"60 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Charles F. Reynolds, MD","affiliation":"University of Pittsburgh","role":"PRINCIPAL_INVESTIGATOR"},{"name":"Eric Lenze, MD","affiliation":"Washington University School of Medicine, St. Louis","role":"PRINCIPAL_INVESTIGATOR"},{"name":"Benoit Mulsant, MD","affiliation":"University of Toronto","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Washington University School of Medicine, St. Louis","city":"St Louis","state":"Missouri","zip":"63110","country":"United States","geoPoint":{"lat":38.62727,"lon":-90.19789}},{"facility":"University of Pittsburgh Medical Center","city":"Pittsburgh","state":"Pennsylvania","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}},{"facility":"University of Toronto","city":"Toronto","state":"Ontario","zip":"M6J1H4","country":"Canada","geoPoint":{"lat":43.70643,"lon":-79.39864}}]},"referencesModule":{"references":[{"pmid":"26423182","type":"RESULT","citation":"Lenze EJ, Mulsant BH, Blumberger DM, Karp JF, Newcomer JW, Anderson SJ, Dew MA, Butters MA, Stack JA, Begley AE, Reynolds CF 3rd. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Dec 12;386(10011):2404-12. doi: 10.1016/S0140-6736(15)00308-6. Epub 2015 Sep 27."},{"pmid":"41380347","type":"DERIVED","citation":"Olgiati P, Ferri R, Luca A, Luca M, Serretti A. Anxiety sensitivity in late-life depression. Links to cognitive impairment, insomnia, and health-related quality of life. J Psychiatr Res. 2026 Feb;193:414-423. doi: 10.1016/j.jpsychires.2025.12.012. Epub 2025 Dec 5."},{"pmid":"36961017","type":"DERIVED","citation":"Olgiati P, Fanelli G, Serretti A. Age or age of onset: which is the best criterion to classify late-life depression? Int Clin Psychopharmacol. 2023 Jul 1;38(4):223-230. doi: 10.1097/YIC.0000000000000472. Epub 2023 Mar 21."},{"pmid":"36594430","type":"DERIVED","citation":"Ainsworth NJ, Brender R, Gotlieb N, Zhao H, Blumberger DM, Karp JF, Lenze EJ, Nicol GE, Reynolds CF, Wang W, Mulsant BH. Association between lean muscle mass and treatment-resistant late-life depression in the IRL-GRey randomized controlled trial. Int Psychogeriatr. 2023 Dec;35(12):707-716. doi: 10.1017/S1041610222000862. Epub 2023 Jan 3."},{"pmid":"35771573","type":"DERIVED","citation":"Diniz BS, Mulsant BH, Reynolds CF 3rd, Blumberger DM, Karp JF, Butters MA, Mendes-Silva AP, Vieira EL, Tseng G, Lenze EJ. Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome. JAMA Netw Open. 2022 Jun 1;5(6):e2219678. doi: 10.1001/jamanetworkopen.2022.19678."},{"pmid":"32991792","type":"DERIVED","citation":"Altmann H, Stahl ST, Gebara MA, Lenze EJ, Mulsant BH, Blumberger DM, Reynolds CF 3rd, Karp JF. Coprescribed Benzodiazepines in Older Adults Receiving Antidepressants for Anxiety and Depressive Disorders: Association With Treatment Outcomes. J Clin Psychiatry. 2020 Sep 29;81(6):20m13283. doi: 10.4088/JCP.20m13283."},{"pmid":"31846575","type":"DERIVED","citation":"Buchalter ELF, Oughli HA, Lenze EJ, Dixon D, Miller JP, Blumberger DM, Karp JF, Reynolds CF 3rd, Mulsant BH. Predicting Remission in Late-Life Major Depression: A Clinical Algorithm Based Upon Past Treatment History. J Clin Psychiatry. 2019 Dec 10;80(6):18m12483. doi: 10.4088/JCP.18m12483."},{"pmid":"30358242","type":"DERIVED","citation":"Wei W, Karim HT, Lin C, Mizuno A, Andreescu C, Karp JF, Reynolds CF 3rd, Aizenstein HJ. Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis. J Clin Psychiatry. 2018 Oct 23;79(6):18m12106. doi: 10.4088/JCP.18m12106."},{"pmid":"29924506","type":"DERIVED","citation":"Hsu JH, Mulsant BH, Lenze EJ, Sanches M, Karp JF, Reynolds CF, Blumberger DM. Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial. J Clin Psychiatry. 2018 Jun 19;79(4):17m11764. doi: 10.4088/JCP.17m11764."},{"pmid":"29659205","type":"DERIVED","citation":"Cristancho P, Lenze EJ, Dixon D, Miller JP, Mulsant BH, Reynolds CF 3rd, Butters MA. Executive Function Predicts Antidepressant Treatment Noncompletion in Late-Life Depression. J Clin Psychiatry. 2018 May/Jun;79(3):16m11371. doi: 10.4088/JCP.16m11371."},{"pmid":"28068779","type":"DERIVED","citation":"Marshe VS, Maciukiewicz M, Rej S, Tiwari AK, Sibille E, Blumberger DM, Karp JF, Lenze EJ, Reynolds CF 3rd, Kennedy JL, Mulsant BH, Muller DJ. Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults. Am J Psychiatry. 2017 May 1;174(5):468-475. doi: 10.1176/appi.ajp.2016.16050617. Epub 2017 Jan 10."},{"pmid":"27645461","type":"DERIVED","citation":"Smagula SF, Karim HT, Lenze EJ, Butters MA, Wu GF, Mulsant BH, Reynolds CF, Aizenstein HJ. Gray matter regions statistically mediating the cross-sectional association of eotaxin and set-shifting among older adults with major depressive disorder. Int J Geriatr Psychiatry. 2017 Dec;32(12):1226-1232. doi: 10.1002/gps.4585. Epub 2016 Sep 19."},{"pmid":"27282141","type":"DERIVED","citation":"Smagula SF, Lotrich FE, Aizenstein HJ, Diniz BS, Krystek J, Wu GF, Mulsant BH, Butters MA, Reynolds CF 3rd, Lenze EJ. Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study. Int J Geriatr Psychiatry. 2017 Jun;32(6):692-699. doi: 10.1002/gps.4512. Epub 2016 Jun 10."},{"pmid":"26963689","type":"DERIVED","citation":"Kaneriya SH, Robbins-Welty GA, Smagula SF, Karp JF, Butters MA, Lenze EJ, Mulsant BH, Blumberger D, Anderson SJ, Dew MA, Lotrich F, Aizenstein HJ, Diniz BS, Reynolds CF 3rd. Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression: An Analysis of the IRL-GRey Randomized Clinical Trial. JAMA Psychiatry. 2016 Apr;73(4):329-36. doi: 10.1001/jamapsychiatry.2015.3447."},{"pmid":"26708830","type":"DERIVED","citation":"Kasckow J, Youk A, Anderson SJ, Dew MA, Butters MA, Marron MM, Begley AE, Szanto K, Dombrovski AY, Mulsant BH, Lenze EJ, Reynolds CF 3rd. Trajectories of suicidal ideation in depressed older adults undergoing antidepressant treatment. J Psychiatr Res. 2016 Feb;73:96-101. doi: 10.1016/j.jpsychires.2015.11.004. Epub 2015 Nov 19."},{"pmid":"26288246","type":"DERIVED","citation":"Smagula SF, Butters MA, Anderson SJ, Lenze EJ, Dew MA, Mulsant BH, Lotrich FE, Aizenstein H, Reynolds CF 3rd. Antidepressant Response Trajectories and Associated Clinical Prognostic Factors Among Older Adults. JAMA Psychiatry. 2015 Oct;72(10):1021-8. doi: 10.1001/jamapsychiatry.2015.1324."},{"pmid":"26278231","type":"DERIVED","citation":"Hall CA, Simon KM, Lenze EJ, Dew MA, Begley A, Butters MA, Blumberger DM, Stack JA, Mulsant B, Reynolds CF 3rd. Depression Remission Rates Among Older Black and White Adults: Analyses From the IRL-GREY Trial. Psychiatr Serv. 2015 Dec 1;66(12):1303-11. doi: 10.1176/appi.ps.201400480. Epub 2015 Aug 17."},{"pmid":"23567441","type":"DERIVED","citation":"Joel I, Begley AE, Mulsant BH, Lenze EJ, Mazumdar S, Dew MA, Blumberger D, Butters M, Reynolds CF 3rd; IRL GREY Investigative Team. Dynamic prediction of treatment response in late-life depression. Am J Geriatr Psychiatry. 2014 Feb;22(2):167-76. doi: 10.1016/j.jagp.2012.07.002. Epub 2013 Feb 6."}]}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"468 signed consent. 181 were randomized. Of these 181, 91 randomized to venlafaxine plus aripirazol and 90 to venlafaxine plus placebo. Prior to randomization, 191 responded to venlafaxine; 40 withdrew consent; 41 withdrawn by PI, possible AE, 14 non-compliance; 1 death.","recruitmentDetails":"Participants were recruited at 3 Centers (University of Pittsburgh, Centre for Addiction and Mental Health in Toronto, Canada, and Washington University). The first participant was enrolled July 2009, last finished August 2014.","groups":[{"id":"FG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks."},{"id":"FG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"91"},{"groupId":"FG001","numSubjects":"90"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"87"},{"groupId":"FG001","numSubjects":"83"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"7"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"2"}]},{"type":"subject burden","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"3"}]},{"type":"Lack of Efficacy","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"2"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks."},{"id":"BG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"91"},{"groupId":"BG001","value":"90"},{"groupId":"BG002","value":"181"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEDIAN","dispersionType":"INTER_QUARTILE_RANGE","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"66.4","lowerLimit":"62.8","upperLimit":"71.6"},{"groupId":"BG001","value":"65.7","lowerLimit":"62.8","upperLimit":"69.8"},{"groupId":"BG002","value":"66.0","lowerLimit":"62.8","upperLimit":"70.5"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"52"},{"groupId":"BG001","value":"51"},{"groupId":"BG002","value":"103"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"39"},{"groupId":"BG001","value":"39"},{"groupId":"BG002","value":"78"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS)","description":"The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten item instrument assessing depression symptoms. Possible scores range from 0-60; higher scores indicate greater severity of depression. Remission defined as score of 10 or less based on the MADRS.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants","timeFrame":"12 weeks","groups":[{"id":"OG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks."},{"id":"OG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"91"},{"groupId":"OG001","value":"90"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"44"},{"groupId":"OG001","value":"29"}]}]}]},{"type":"PRIMARY","title":"Akathisia","description":"Percentage of participants who developed clinically significant akathisia.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants","timeFrame":"12 weeks","groups":[{"id":"OG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks."},{"id":"OG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"91"},{"groupId":"OG001","value":"90"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"26.7"},{"groupId":"OG001","value":"12.2"}]}]}]},{"type":"PRIMARY","title":"Weight","description":"Weight change in kilograms","populationDescription":"The number of participants analyzed is lower due to missing data attributable to dropouts. The information obtained is from figure 3B in the manuscript","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"kilograms","timeFrame":"Baseline through12 weeks","groups":[{"id":"OG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks."},{"id":"OG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"84"},{"groupId":"OG001","value":"85"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1.93","spread":"3.00"},{"groupId":"OG001","value":"0.01","spread":"3.15"}]}]}]},{"type":"PRIMARY","title":"Parkinsonism","description":"Percentage of participants who develop signs of parkinsonism","populationDescription":"We have a lower number of participants analyzed due to dropouts and missed assessments.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants","timeFrame":"12weeks","groups":[{"id":"OG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks."},{"id":"OG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"86"},{"groupId":"OG001","value":"81"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"17.4"},{"groupId":"OG001","value":"2.5"}]}]}]},{"type":"SECONDARY","title":"Emergent Suicidal Ideation in Those With no Ideation at the Start of Treatment","description":"percentage of participants who reported suicidal ideation during treatment but not at baseline","populationDescription":"It is a smaller number of participants restricted to those who did not report any suicidal ideation at baseline. This is in Table 3of the manuscript","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percent of participants","timeFrame":"12 weeks","groups":[{"id":"OG000","title":"1: Venlafaxine Plus Aripiprazole","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks."},{"id":"OG001","title":"2: Placebo Comparator","description":"antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo\n\nvenlafaxine plus placebo: Dosage varies. 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