Phase 4
N=181
Incomplete Response in Late Life Depression: Getting to Remission (IRL GREY)
Depression
Bottom Line
View on ClinicalTrials.gov: NCT00892047 ↗Enrolled (actual)
181
Serious AEs
3.3%
Results posted
Dec 2015
Primary outcome: Primary: Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS) — 44; 29 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- venlafaxine XR plus aripiprazole (Drug); venlafaxine plus placebo (Drug)
- Age
- Adult, Older Adult · 60+ yrs
- Sex
- All
- Sponsor
- University of Pittsburgh
- Primary completion
- Sep 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS) |
44; 29 | — |
| PRIMARY Akathisia |
26.7; 12.2 | — |
| PRIMARY Weight |
1.93; 0.01 | — |
| PRIMARY Parkinsonism |
17.4; 2.5 | — |
| SECONDARY Emergent Suicidal Ideation in Those With no Ideation at the Start of Treatment |
21.3; 29.2 | — |
| SECONDARY QTc Prolongation on EKG (to Greater or Equal to 480 Msec) |
1.3; 0 | — |
Summary
The primary aims of this study are to:
1. 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).
2. Assess the tolerability of aripiprazole in TRLLD with a focus on adiposity and akathisia/restlessness.
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:
1. 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.
2. Examine genetic predictors (phase 1) and moderators (phase 2-3) of treatment outcomes, while controlling for drug exposure.
Hypothesis 4: Selected polymorphisms will reduce remission rate with venlafaxine and will reduce efficacy and tolerability with aripiprazole.
Eligibility Criteria
Inclusion Criteria
- Age > 60 years.
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV.
- MADRS ≥ 15.
Exclusion Criteria
- Inability to provide informed consent.
- Depressive symptoms not severe enough (i.e., MADRS 225 mg/d) plus aripiprazole (>10 mg/d).
- 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).
- Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
- 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.
- 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.
Data sourced from ClinicalTrials.gov (NCT00892047). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.