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Sponsored by: |
University of Pittsburgh |
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Information provided by: | University of Pittsburgh |
ClinicalTrials.gov Identifier: | NCT00892047 |
The primary aims of this study are to:
Assess the efficacy of aripiprazole augmentation for the acute and continuation treatment of TRLLD.
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).
Hypothesis 2: Aripiprazole will be associated with a higher rate of clinically significant akathisia and increased adiposity than placebo.
The Secondary/exploratory aims of this study are to:
Examine anxiety, medical burden, and executive impairment as moderators of aripiprazole augmentation efficacy in TRLLD.
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.
Hypothesis 4: Selected polymorphisms will reduce remission rate with venlafaxine and will reduce efficacy and tolerability with aripiprazole.
Condition | Intervention | Phase |
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Depression |
Drug: venlafaxine XR plus aripiprazole Drug: venlafaxine plus placebo |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Incomplete Response in Late Life Depression: Getting to Remission |
Estimated Enrollment: | 500 |
Study Start Date: | August 2009 |
Estimated Study Completion Date: | July 2014 |
Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: venlafaxine plus aripiprazole: Experimental
antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo
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Drug: venlafaxine 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.
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2: Placebo Comparator: Experimental
antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo
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Drug: venlafaxine 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.
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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.
This 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.
In 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.
Ages Eligible for Study: | 60 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
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.
Contact: Jacqueline Stack, M.S.N. | 412-246-6006 | stackja@upmc.edu |
Contact: Jill Houle, B.S.E. | 412-246-6006 | houleja@upmc.edu |
United States, Pennsylvania | |
University of Pittsburgh | |
Pittsburgh, Pennsylvania, United States, 15213 | |
University of Pittsburgh Medical Center | |
Pittsburgh, Pennsylvania, United States |
Principal Investigator: | Charles F. Reynolds, MD | University of Pittsburgh |
Principal Investigator: | Eric Lenze, MD | Washington University School of Medicine |
Principal Investigator: | Benoit Mulsant, MD | University of Toronto |
Responsible Party: | University of Pittsburgh ( Charles F.Reynolds III, MD ) |
Study ID Numbers: | MH083660-01A1 |
Study First Received: | April 29, 2009 |
Last Updated: | May 1, 2009 |
ClinicalTrials.gov Identifier: | NCT00892047 History of Changes |
Health Authority: | United States: Institutional Review Board |
Depression Aripiprazole Venlafaxine Partial Remission |
Augmentation strategy Treatment resistance Elderly Late-life |
Neurotransmitter Agents Tranquilizing Agents Depression Psychotropic Drugs Central Nervous System Depressants Antipsychotic Agents Depressive Disorder Serotonin Uptake Inhibitors |
Serotonin Behavioral Symptoms Mental Disorders Venlafaxine Mood Disorders Aripiprazole Antidepressive Agents, Second-Generation Antidepressive Agents |
Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Tranquilizing Agents Depression Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Psychotropic Drugs Central Nervous System Depressants Antipsychotic Agents Depressive Disorder Serotonin Uptake Inhibitors |
Pharmacologic Actions Behavioral Symptoms Serotonin Agents Mental Disorders Therapeutic Uses Venlafaxine Mood Disorders Aripiprazole Antidepressive Agents, Second-Generation Central Nervous System Agents Antidepressive Agents |