Treatment-resistant Late-life Depression Research Articles

0959 Sleep and Pharmacotherapy in Treatment-Resistant Late-life Depression: Findings from the OPTIMUM Clinical Trial

0959 Sleep and Pharmacotherapy in Treatment-Resistant Late-life Depression: Findings from the OPTIMUM Clinical Trial

S12: Recent advances in therapies for late-life neuropsychiatric disorder

Symposium OverviewThis international symposium combining experts from Canada, Australia and the USA and supported by the American Association for Geriatric Psychiatry will present an update on the recent advances in therapeutic interventions for late life mood and cognitive disorders, including late life depression, anxiety and apathy associated with dementia, and preventive strategies including mind-body interventions. Four leaders of the field will present the summary of novel studies: starting with Dr. Benoit Mulsant (CA) presenting the results of the recently completed OPTIMUM study of novel strategies optimizing treatment of late-life treatment resistant depression. He will be followed by Dr. Krista Lanctot’ (CA) update on novel therapies for apathy associated with Alzheimer’s disease, and Dr Nancy Pachana (AU) will present on non-pharmacological approaches to treatment of anxiety associated with neurodegenerative disorders. Finally, Dr. Helen Lavretsky (USA) will present on the recent studies of mind-body therapies used to treat and prevent late life depression and cognitive decline, along with the discussion of the underlying neurobiological mechanisms. The panel will conclude with a brief discussion of future directions in the development of therapeutic interventions.Treatment-resistant depression in late life has been understudied and is lacking evidence supporting augmentation or switching strategies. Recently completed OPTIMUM multi-site study (funded by the PCORI) sought to compare effectiveness of augmentation strategies (bupropion or aripiprazole) to switch to bupropion, in the first step of 1-week acute treatment followed by randomization into the 2nd step of augmentation with Lithium or switch to nortriptyline. The augmentation strategies in the first step produced the most robust response compared to switching, and did not differ in the 2nd step. Primary outcomes included remission rates and wellbeing measures. A discussion of future directions will be provided at the end of this presentation.In those with Alzheimer’s disease, apathy is common and associated with decreased quality of life, increased risk of decline and increased mortality. As such, apathy is increasingly recognized as an important treatment target. Recent advances in diagnosis and treatment will be reviewed.In this presentation, several methodological issues will be discussed, such the importance and prevalence of apathy in Alzheimer’s disease (AD); current diagnostic criteria for apathy in neurocognitive disorders, and will present the results of recent pharmacologic interventions for apathy in AD.In this presentation, new focused and innovative treatments for anxiety in persons with Alzheimer's and Parkinson's disease with co-morbid anxiety will be discussed. Anxiety is common in Alzheimer's Disease and Parkinson's disease and contributes to increased disability and poorer quality of life. Yet only a small fraction of such patients received any form of treatment for mental health issues. Non-pharmacological approaches to address anxiety are advantageous in these populations. Research on tailored CBT and innovations such as virtual reality approaches for these groups will be discussed.Standard pharmacological therapies for treatment of late life depression offer limited efficacy with the downside of adverse events and drug-drug interaction. Novel strategies are needed for more effective and safe treatment and prevention strategies for mood and cognitive disorders in late life. This presentation will focus on the recently completed studies of Tai Chi for treatment of late life depression, and yoga for prevention of cognitive decline in older women at risk for Alzheimer’s disease. Neural and peripheral biomarkers of treatment response will be described. Future directions in mind-body therapies research will be outlined.

Change in Patient-Centered Outcomes of Psychological Well-Being, Sleep, and Suicidality Following Treatment with Intravenous Ketamine for Late-Life Treatment-Resistant Depression

Change in Patient-Centered Outcomes of Psychological Well-Being, Sleep, and Suicidality Following Treatment with Intravenous Ketamine for Late-Life Treatment-Resistant Depression

A Review of Therapeutics for Treatment-Resistant Depression in the Older Adult.

One-third of older adults with depression meet criteria for treatment resistance, typically defined as a lack of response to two or more adequate trials of an antidepressant. Treatment resistance contributes to an unfavorable prognosis, compromised medical outcomes, heightened disability, accelerated cognitive decline, and an elevated risk of developing dementia. Despite this significant morbidity, evidence is sparse for how to proceed with treatment in this population. Non-pharmacologic therapy (e.g., diet, psychotherapy) can be utilized as adjunctive therapy, despite little published evidence of benefit, given that the risks are low. Pharmacotherapy trials in the treatment-resistant late-life depression population lack strong methods and external validity; however, the use of venlafaxine as monotherapy and add-on therapy, as well as lithium, bupropion, or aripiprazole as add-on therapy to standard antidepressant therapy, have enough evidence that a trial with appropriate monitoring is a prudent strategy. Electroconvulsive therapy remains a well-studied safe therapy, especially when used as maintenance treatment once an initial cycle is completed but is traditionally underutilized in the treatment-resistant late-life depression population. Ensuring non-pharmacologic and pharmacologic strategies are optimized and given a sufficient trial in those with treatment-resistant late-life depression is the best we can do for this vulnerable population.

Effect of prior pharmacotherapy on remission with sequential bilateral theta-burst versus standard bilateral repetitive transcranial magnetic stimulation in treatment-resistant late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes.

Neural complexity EEG biomarkers of rapid and post-rapid ketamine effects in late-life treatment-resistant depression: a randomized control trial

Ketamine is an effective intervention for treatment-resistant depression (TRD), including late-in-life (LL-TRD). The proposed mechanism of antidepressant effects of ketamine is a glutamatergic surge, which can be measured by electroencephalogram (EEG) gamma oscillations. Yet, non-linear EEG biomarkers of ketamine effects such as neural complexity are needed to capture broader systemic effects, represent the level of organization of synaptic communication, and elucidate mechanisms of action for treatment responders. In a secondary analysis of a randomized control trial, we investigated two EEG neural complexity markers (Lempel-Ziv complexity [LZC] and multiscale entropy [MSE]) of rapid (baseline to 240 min) and post-rapid ketamine (24 h and 7 days) effects after one 40-min infusion of IV ketamine or midazolam (active control) in 33 military veterans with LL-TRD. We also studied the relationship between complexity and Montgomery-Åsberg Depression Rating Scale score change at 7 days post-infusion. We found that LZC and MSE both increased 30 min post-infusion, with effects not localized to a single timescale for MSE. Post-rapid effects of reduced complexity with ketamine were observed for MSE. No relationship was observed between complexity and reduction in depressive symptoms. Our findings support the hypothesis that a single sub-anesthetic ketamine infusion has time-varying effects on system-wide contributions to the evoked glutamatergic surge in LL-TRD. Further, changes to complexity were observable outside the time-window previously shown for effects on gamma oscillations. These preliminary results have clinical implications in providing a functional marker of ketamine that is non-linear, amplitude-independent, and represents larger dynamic properties, providing strong advantages over linear measures in highlighting ketamine’s effects.

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition

Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d=0.61), and these improvements were sustained in the continuation phase. This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

P300. Neural and Cognitive Effects of Hearing Loss in Treatment-Resistant Late-Life Depression

Research has revealed the important neuropsychiatric consequences of hearing loss (HL) in older adults. Both HL and treatment-resistant late-life depression (LLD) have been demonstrated to be significant risk factors for dementia, but no study has evaluated the neurocognitive effects of HL in LLD.

Neural and Cognitive Effects of Hearing Loss in Treatment-Resistant Late-Life Depression

<h3>Introduction</h3> Recent research has revealed the important neuropsychiatric and brain consequences of hearing loss (HL) in older adults. Both HL and treatment-resistant late-life depression (LLD) have been demonstrated to be significant risk factors for cognitive decline and dementia. While studies have evaluated the pair-wise links between HL, LLD, and cognitive impairment, no study has evaluated the neural and cognitive effects of HL in a population with LLD. <h3>Methods</h3> Data was utilized from the OPTIMUM study, a large ongoing multicenter clinical trial recruiting older adults with LLD who have failed two or more antidepressant treatments, who are randomized to different antidepressant treatment groups. OPTIMUM-Neuro is enrolling a subset of the original OPTIMUM cohort to conduct longitudinal neurocognitive assessments and advanced neuroimaging. Pure tone audiometric hearing assessments were also performed on a subset of participants enrolled in OPTIMUM-Neuro. Among the treatment resistant LLD population in OPTIMUM-Neuro, we hypothesized that the presence of HL (pure tone average [PTA]) would be associated with greater impairment on cognitive (executive function and episodic memory) and structural brain (cortical thickness of primary and secondary auditory cortex and volume of hippocampus) outcomes at study baseline. <h3>Results</h3> Data is reported for a sample of N=126 that have been analyzed to-date, of whom N=42 have structural MRI data available. However, we aim to analyze N=200 participants (we currently have N=183 participants with hearing data) by the ACNP annual meeting. Among the sample analyzed to-date, 47.6% participants have HL and unfortunately only 30.0% participants with HL reported wearing hearing aids. At baseline, worse PTA was associated with auditory cortical thinning (R superior temporal sulcus [β=-0.0058, t=-2.57, p=0.0145]; R supramarginal gyrus sulcus [β=-0.00415, t=-2.44, p=0.0198]; R superior parietal cortex [β=-0.00474, t=-2.31, p=0.0296],) but no effect on hippocampal volume was found (R hippocampus [β=5.601, t=0.96, p=0.342]; L hippocampus [β=-0.509, t=-0.09, p=0.927]). At baseline, worse PTA was associated with impairment in executive functioning (Task switching [β= -0.054, t=-2.00, p=0.047]), visuospatial/constructional abilities (β=-0.21, t=-2.29 p=0.024]) and higher dementia rating (Clinical Dementia Rating Scale [β=0.21, t=2.77, p=0.007]), but no effect of PTA on other cognitive domains was found. <h3>Conclusions</h3> In a sample with treatment resistant LLD, HL was associated with atrophy of the primary and secondary auditory cortex and worse performance on assessments of executive functioning. Despite these adverse neuropsychiatric and brain effects of HL, it is unfortunate that hearing aids are infrequently utilized. <h3>This research was funded by</h3> Leon Levy Foundation

Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) seven days after a 40 minute intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free U.S. military veterans (mean age 62; range: 55 – 72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision-rules terminated KET 0.1 (N=4) and KET 0.25 (N=5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N=11; response rate = 70%) compared to MID (N=13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.

420 - Ketamine treatment in geriatric depression

Treatment resistant depression can be very disabling and has a significant negative impact on a patient, their family or caregivers, and the society. There is a growing evidence on the efficacy and safety of ketamine for treatment resistant depression. Ketamine is a racemate consisting of esketamine and arketamine, is an N-methyl D-aspartate receptor antagonist and comes in different formulations and in fact intranasal ketamine is FDA-approved in the US. Despite the existing evidence and FDA approval for treatment resistant depression, data on older individuals remains limited. Late life depression especially those that are treatment resistant can be very disabling, with significant functional and cognitive impairments, increased morbidity and mortality, and the psychosocial burdens.This presentation describes outcomes for 2 cases of older individuals with treatment resistant depression who were treated with intranasal ketamine. One improved, and one did not. The scarce available literature of the use of ketamine in the geriatric population shows ketamine is well tolerated and effective. Remission rates in 3 separate show remission rates of 46.5%, 57% and 69.5% respectively. The discussion will include a review of the mechanism of action of ketamine as a novel antidepressant, the mixed evidence for its role in treatment resistant late life depression, and the practical and operational aspects relevant to running a ketamine clinic.

Optimizing Outcomes of Treatment - Resistant Depression in Older Adults (OPTIMUM): Study Design and Sample

<h3>Introduction</h3> Late-life treatment resistant depression (LLTRD) is common in older adults as many fail to respond to first-line pharmacotherapies such as SSRIs and SNRIs. LLTRD is associated with deleterious effects as it leads to worsening of medical outcomes, increased disability, and worsening of cognitive dysfunction. Thus, there remains a need to determine more effective and safer treatments for LLTRD. Next line treatments, including augmentation strategies (e.g., with aripiprazole, bupropion, or lithium) or switching to a tricyclic antidepressant have not been studied systematically in older adults. OPTIMUM is a pragmatic randomized clinical trial (RCT) in which we compared strategies of augmentation vs switching in older adults (60 years and older) with TRD in a five- center collaborative study funded by the Patient-Centered Outcomes Research Institute (PCORI). OPTIMUM compared the effectiveness and risks of several strategies using a two-step protocol. <h3>Methods</h3> Participants were recruited and randomized if they were 60 years and older, met the <i>Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition</i> (DSM-5) criteria for Major Depressive Disorder and had a score of 10 or higher on the Patient Health Questionnaire (PHQ-9), despite having been treated with at least two antidepressants with an adequate dosage and for at least four weeks (with previous antidepressants being different from the medications being tested in OPTIMUM). Upon study entry, participants either continued their index antidepressant, if assigned to augmentation, or tapered it off, if assigned to switching. Randomization occurred in two steps, with each step lasting 10 weeks. In Step 1, participants were randomized to one of three strategies: augmentation with aripiprazole, augmentation with bupropion, or switch to bupropion. Treatment effectiveness was assessed using the Montgomery Asberg Depression Rating Scale (MADRS) after ten weeks of treatment. Those who do not remit (defined as a MADRS score <10) proceed to Step 2 where they were randomized to either lithium augmentation of an index antidepressant or switching to nortriptyline. <h3>Results</h3> Step 1 involved 621 participants, of which 212 were randomized to augmentation with aripiprazole, 206 to augmentation with bupropion, and 203 to a switch to bupropion. Of these 621 Step-1 participants, 269 (43%) were >70 years, 415 (67%) were female, and 98 (16%) were non-Caucasian. Step 2 involved 251 participants of which 127 were randomized to augmentation to augmentation with lithium and 124 to a switch to nortriptyline. Of these 251 Step-2 participants, 104 (41%) were >70 years, 176 (70%) were female, and 26 (10%) were non-Caucasian. <h3>Conclusions</h3> OPTIMUM is a pragmatic RCT comparing the effectiveness, tolerability, and safety of several augmentation and switch strategies in a large and diverse group of patients with LLTRD. The study responds to the need of clinicians and patients to make treatment decisions and improve the quality of life of their patients with LLTRD based on evidence on the benefits and risks of commonly used treatment options. <h3>Funding</h3> This research was funded through a Patient-Centered Outcomes Research Institute (PCORI) award TRD-1511- 33321.

Association between increased theta cordance and early response to ECT in late-life depression.

More than half of patients with major depression who do not respond to initial antidepressants become treatment resistant (TRD), and while electroconvulsive therapy (ECT) is effective, it involves anesthesia and other medical risks that are of concern in geriatric patients. Past studies have suggested that theta cordance (TC), a correlate of cerebral metabolism measured by electroencephalography, could guide treatment decisions related to patient selection and engagement of the therapeutic target. Eight patients with late-life treatment resistant depression (LL-TRD) underwent magnetoencephalography (MEG) at baseline and following seven sessions of ECT. We tested whether the mean and regional frontal cortex TC were able to differentiate early responders from nonresponders. Five patients whose depression severity decreased by >30% after seven sessions were considered early responders. We found no baseline differences in mean frontal TC between early responders compared with nonresponders, but early responders exhibited a significant increase in TC following ECT. Further, we found that compared with nonresponders, early responders exhibited a greater change in TC specifically within the right prefrontal cortex. These results support the hypothesis that increases in frontal TC are associated with antidepressant response. We expand on previous findings by showing that this change is specific to the right prefrontal cortex. Validation of this neural marker could contribute to improved ECT outcomes, by informing early clinical decisions about the acute efficacy of this treatment.

Bayesian adaptive randomization trial of intravenous ketamine for veterans with late-life, treatment-resistant depression

More than eleven million U.S. Veterans are at least 65 years of age, an age group of which almost 20% suffers from clinically significant depressive symptoms. Available pharmacological treatments are suboptimal for patients, including veterans, with late-life depression. Ketamine has emerged as a potentially promising rapid-acting therapy for treatment-resistant depression (TRD). However, few studies have examined the safety, tolerability and efficacy of ketamine therapy for older adults with late-life TRD (LL-TRD). This study uses an adaptive randomization design to test the safety, tolerability, efficacy, and durability of three distinct, single sub-anesthetic doses of intravenous (IV) ketamine versus a single dose of active placebo (midazolam) in older depressed veterans. As the study progresses, Bayesian adaptive randomization recalibrates randomization ratios to allocate more participants to conditions demonstrating greater promise and fewer participants to conditions with less promise. Secondary analyses explore clinical and biological moderating and mediating factors of rapid treatment response. Results are expected to inform both the viability of ketamine treatment and optimal dosing strategies for patients with LL-TRD.

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM): Study Design and Treatment Characteristics of the First 396 Participants Randomized

Evidence from clinical trials comparing effectiveness and safety of pharmacological strategies in older adults unresponsive to first-line antidepressants is limited. The study, Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM), tests three hypotheses concerning pharmacotherapy strategies for treatment-resistant late-life depression: 1) augmentation strategies will provide greater improvement than switching monotherapies; 2) augmentation strategies will have lower tolerability and more safety concerns than switching monotherapies; and 3) age will moderate the effectiveness and safety differences between treatment strategies. The authors describe the methodology, processes for stakeholder engagement, challenges, and lessons learned in the early phases of OPTIMUM. This pragmatic randomized clinical trial located in five North American regions will enroll 1,500 participants aged 60 years and older unresponsive to two or more antidepressant trials. The authors evaluate two strategies (medication augmentation versus switch) using four medications (aripiprazole, bupropion, lithium, and nortriptyline) via a stepwise, prespecified protocol. Primary outcomes include: 1) symptom remission (Montgomery Asberg Depression scale ≤10); 2) psychological well-being, comprising positive affect, general life satisfaction, and purpose; and 3) safety (rates of serious adverse events and prevalence of falls and fall-related injuries). To date, 396 participants have been randomized. The authors report on four challenges: 1) engagement and recruitment; 2) increasing polypharmacy in older adults, resulting in potentially hazardous scenarios; 3) reporting adverse events and procedure standardization across sites; and 4) dissemination of results. Solutions to these challenges, including early inclusion of stake holders, will inform future pragmatic studies in older adults with depression.

Brief behavioral treatment for insomnia in older adults with late-life treatment-resistant depression and insomnia: a pilot study.

Brief Behavioral Treatment for Insomnia (BBTI) is an efficacious treatment of insomnia in older adults. Behavioral treatments for insomnia can also improve depression. However, it is unknown if BBTI is feasible or has an effect in patients with insomnia and late-life treatment resistant depression (LLTRD). The aims of this study were two-fold, to test: 1) the feasibility (defined by acceptability and retention rates) of BBTI and 2) the therapeutic potency of BBTI on symptoms of insomnia and depression. Eleven older Veterans with LLTRD and insomnia were recruited in a randomized control trial to receive immediate (4-weeks of BBTI followed by 3-weeks of phone call check-ins and a final in-person 8-week assessment) or delayed (3-weeks of treatment as usual [wait-list control] followed by 4-weeks of BBTI and a final in-person 8-week assessment) BBTI. The primary outcome measures included the Patient Health Questionnaire (minus the sleep item) and the Insomnia Severity Index. BBTI was found to be feasible in older Veterans with insomnia and LLTRD; all participants recommended BBTI and retention rates were 90.9%. There was no difference in treatment effect between the immediate BBTI and delayed BBTI groups at week 4. After both groups (immediate and delayed) received BBTI, improvements were seen in both insomnia (d = 1.06) and depression (d = 0.54) scores. BBTI is a feasible treatment for insomnia in older adults with LLTRD. BBTI may be an effective adjunctive treatment for depression. Larger adequately-powered trials are required to confirm these preliminary findings.

Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial.

Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD. Between 2009 and 2013, depressed older adults who did not remit with venlafaxine were randomized to aripiprazole or placebo in a 12-week trial. Participants were 60 years or older and met DSM-IV-TR criteria for major depressive episode with at least moderate symptoms. The presence of akathisia and parkinsonism was measured at each visit using the Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS), respectively. In an exploratory analysis, we examined a broad set of potential clinical predictors and correlates: age, sex, ethnicity, weight, medical comorbidity, baseline anxiety severity, depression severity, concomitant medications including rescue medications, and aripiprazole dosage. Twenty-four (26.7%) of 90 participants randomized to aripiprazole and who had akathisia scores available developed akathisia compared to 11 (12.2%) of 90 randomized to placebo. Greater depression severity was the main predictor of treatment-emergent akathisia. Most participants who developed akathisia improved over time, especially with reductions in dosage. Fifteen (16.5%) of 91 participants taking aripiprazole and who had parkinsonism scores available developed parkinsonism, but no clinical predictors or correlates were identified. Akathisia is a common side effect of aripiprazole, but it is typically mild and responds to dose reduction. Patients with greater baseline depression may warrant closer monitoring for akathisia. More research is needed to understand the course and predictors of treatment-emergent EPS with antipsychotic augmentation for treatment-resistant LLD. ClinicalTrials.gov identifier: NCT00892047.

Poster Number: EI 67 - Brief Behavioral Treatmnet for Insomnia in Older Veterans with Late Life Treatment Resistant Depression

Poster Number: EI 67 - Brief Behavioral Treatmnet for Insomnia in Older Veterans with Late Life Treatment Resistant Depression

Use of Ketamine in Elderly Patients with Treatment-Resistant Depression.

The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports. We discuss the use of ketamine for late-life TRD and present two cases where ketamine led to a significant and sustained improvement in depressive symptoms. Ketamine is a promising treatment for geriatric patients with TRD. Further studies in the elderly will provide valuable insights into the use of ketamine for a population much in need of safe and effective treatments for TRD.

Specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression.

To identify which specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression. This is a secondary analysis of data from a late-life treatment resistant depression trial examining the safety and efficacy of aripiprazole augmentation. Participants aged 60 and above were randomized to aripiprazole augmentation (N=91) versus placebo (N=90). The main outcome was depression remission. Clinical predictors included individual Montgomery-Asberg Depression Rating Scale (MADRS) item scores categorized as symptomatic (scores >2) or nonsymptomatic (scores ≤2). Three MADRS items predicted depression remission with aripiprazole augmentation: symptomatic scores on sleep disturbance and nonsymptomatic scores on apparent sadness and inability to feel. The 2-way and 3-way interaction terms of these MADRS items were not significant predictors of remission; therefore, the models' ability to predict remission was not improved by combining the significant MADRS items. The identification of specific depressive symptoms, which can be clinically assessed, can be used to inform treatment decisions. Older adults with treatment resistant depression that present with sleep disturbances, lack of apparent sadness, or lack of inability to feel should be considered for aripiprazole augmentation.