Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression

Lenze, Eric J.; Mulsant, Benoit H.; Roose, Steven P.; Lavretsky, Helen; Reynolds, Charles F.; Blumberger, Daniel M.; Brown, Patrick J.; Cristancho, Pilar; Flint, Alastair J.; Gebara, Marie Anne; Gettinger, Torie R; Lenard, Emily; Miller, J. Philip; Nicol, Ginger E.; Oughli, Hanadi Ajam; Pham, Vy; Rollman, Bruce L.; Yang, Lei; Karp, Jordan F.

doi:10.1056/nejmoa2204462

Cited by 39 publications

(28 citation statements)

References 33 publications

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“…Our participants experienced an 8.9 T‐score increase in overall psychological well‐being with 4 weeks of treatment with IV ketamine. In a recent large comparative study of antidepressant pharmacotherapy in late‐life TRD conducted by the same investigators using the same measure of psychological well‐being, participants experienced increases of 4.1, 3.7, and 2.6 over 10 weeks of treatment with aripiprazole, bupropion, and lithium, respectively 8 . A randomized study is needed to compare IV ketamine and standard pharmacotherapy in older adults with TRD.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment‐resistant depression (TRD) is typically defined as depression that does not improve after at least two adequate trials of antidepressant medications 6,7 . In a recent comparative effectiveness trial in older adults with TRD, remission rates with commonly used pharmacotherapy strategies were <30% 8 . Additional novel treatment options for TRD in older adults are needed.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 In a recent comparative effectiveness trial in older adults with TRD, remission rates with commonly used pharmacotherapy strategies were <30%. 8 Additional novel treatment options for TRD in older adults are needed.…”

Section: Introductionmentioning

confidence: 99%

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Change in patient‐centered outcomes of psychological well‐being, sleep, and suicidality following treatment with intravenous ketamine for late‐life treatment‐resistant depression

Vanderschelden

Gebara

Oughli

et al. 2023

Int J Geriat Psychiatry

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Objective To examine whether psychological well‐being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late‐life treatment‐resistant depression (TRD). Methods This is an analysis of secondary outcomes in an open‐label late‐life TRD study examining the safety, tolerability, and feasibility of IV ketamine infusions. In the acute phase, participants (N = 25) aged 60 years or older received twice‐a‐week IV ketamine for 4 weeks. Then, participants with Montgomery‐Asberg Depression Rating Scale (MADRS) total score <10 or ≥ 30% reduction from baseline proceeded to the continuation phase, an additional four weeks of once‐a‐week IV ketamine. The secondary outcomes analyzed here are based on the National Institute of Health Toolbox Psychological Well‐Being subscales for Positive Affect and General Life Satisfaction, the Pittsburgh Sleep Quality Index, and the Scale for Suicidal Ideation. Results Psychological well‐being, sleep, and suicidality improved during the acute phase and those improvements were sustained during the continuation phase. Greater improvements in measures of psychological well‐being and sleep were seen in participants who had greater improvements in MADRS scores and moved onto the continuation phase. All but one of the few participants with high suicidality at baseline improved; there were no cases of treatment‐emergent suicidality. Conclusions Psychological well‐being, sleep, and suicidality improved in participants with late‐life TRD who received IV ketamine for 8 weeks. A future larger and longer controlled trial is needed to confirm and extend these findings. Registration ClinicalTrials.gov identifier: NCT04504175.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Change in patient‐centered outcomes of psychological well‐being, sleep, and suicidality following treatment with intravenous ketamine for late‐life treatment‐resistant depression

Vanderschelden

Gebara

Oughli

et al. 2023

Int J Geriat Psychiatry

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“…Antidepressants remain beneficial, with a number needed to treat (NNT) for an antidepressant response being 6.7 (95% CI, 4.8–10) [ 234 , 238 ]. As in younger adults, augmentation strategies in LLD are more efficacious than strategies involving a switch to a different antidepressant [ 239 ]. Methylphenidate augmentation of an SSRI is superior to monotherapy with either agent alone [ 240 ].…”

Section: Updates On Established Somatic Treatmentsmentioning

confidence: 99%

“…Methylphenidate augmentation of an SSRI is superior to monotherapy with either agent alone [ 240 ]. Augmentation with lithium, bupropion, or aripiprazole in patients who did not respond to monotherapy can be well-tolerated and improve depressive symptoms [ 239 , 241 , 242 ]. Despite clear benefits of augmentation, the likelihood of achieving remission decreases with increasing number of failed antidepressant trials within the current episode [ 243 ].…”

Section: Updates On Established Somatic Treatmentsmentioning

confidence: 99%

Biological factors influencing depression in later life: role of aging processes and treatment implications

Szymkowicz,

Gerlach,

Homiack

et al. 2023

Transl Psychiatry

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Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic–pituitary–adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.

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Alcohol and substance use in older adults with treatment‐resistant depression

Srifuengfung,

Lenze,

Roose

et al. 2024

Int J Geriat Psychiatry

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IntroductionAlcohol and substance use are increasing in older adults, many of whom have depression, and treatment in this context may be more hazardous. We assessed alcohol and other substance use patterns in older adults with treatment‐resistant depression (TRD). We examined patient characteristics associated with higher alcohol consumption and examined the moderating effect of alcohol on the association between clinical variables and falls during antidepressant treatment.MethodsThis secondary and exploratory analysis used baseline clinical data and data on falls during treatment from a large randomized antidepressant trial in older adults with TRD (the OPTIMUM trial). Multivariable ordinal logistic regression was used to identify variables associated with higher alcohol use. An interaction model was used to evaluate the moderating effect of alcohol on falls during treatment.ResultsOf 687 participants, 51% acknowledged using alcohol: 10% were hazardous drinkers (AUDIT‐10 score ≥5) and 41% were low‐risk drinkers (score 1–4). Benzodiazepine use was seen in 24% of all participants and in 21% of drinkers. Use of other substances (mostly cannabis) was associated with alcohol consumption: it was seen in 5%, 9%, and 15% of abstainers, low‐risk drinkers, and hazardous drinkers, respectively. Unexpectedly, use of other substances predicted increased risk of falls during antidepressant treatment only in abstainers.ConclusionsOne‐half of older adults with TRD in this study acknowledged using alcohol. Use of alcohol concurrent with benzodiazepine and other substances was common. Risks—such as falls—of using alcohol and other substances during antidepressant treatment needs further study.

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Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression

Cited by 39 publications

References 33 publications

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

Biological factors influencing depression in later life: role of aging processes and treatment implications

Alcohol and substance use in older adults with treatment‐resistant depression

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