Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression

Kaneriya, Shriya H.; Robbins-Welty, Gregg A.; Smagula, Stephen F.; Karp, Jordan F.; Butters, Meryl A.; Lenze, Eric J.; Mulsant, Benoit H.; Blumberger, Daniel M.; Anderson, Stewart J.; Dew, Mary Amanda; Lotrich, Francis E.; Aizenstein, Howard J.; Diniz, Breno S.; Reynolds, Charles F.

doi:10.1001/jamapsychiatry.2015.3447

Cited by 50 publications

(43 citation statements)

References 28 publications

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“…Executive dysfunction is persistently associated with poorer acute response to antidepressant treatment and longer time to remission. 20,24 The difference in executive function findings between 3- and 12-month analyses may be related to individuals with executive deficits having a longer time to remission or, if they remit early, greater likelihood of relapse over that year.…”

Section: Discussionmentioning

confidence: 99%

“…In this model, underlying neurodegenerative or vascular processes contribute to both cognitive decline and also negatively affect neural circuits involved in mood regulation. 20 Damage to such circuits may predispose individuals to depression and diminish the ability of antidepressants to modify brain function and connectivity, resulting in poorer clinical response. 21 Thus clinically relevant depressive symptoms in context of mild cognitive symptoms may be an early marker of brain pathology.…”

Section: Introductionmentioning

confidence: 99%

“…Deficits in executive dysfunction and other cognitive domains are associated with poorer acute antidepressant medication responses and persistent long-term depressive symptoms. 20,24–26 Successful antidepressant treatment may improve cognitive performance acutely 27 although performance may not reach age-adjusted levels and deficits often persist despite successful treatment. 5,28–30 Moreover, individuals with persistent depressive symptoms exhibit more rapid pathological brain aging, 31,32 although it is unclear whether persistent depression hastens brain aging or whether brain aging influences the clinical antidepressant response.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

Riddle

Potter

McQuoid

et al. 2017

The American Journal of Geriatric Psychiatry

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Objectives Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. We examined age of depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response). Design A longitudinal study of late-life depression in an academic center. Participants 273 depressed and 164 never-depressed community dwelling elders aged 60 years or older were followed on average for over five years. Measurements Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. Results Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than the late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3- and 12-months exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. 3-month remitters also exhibited a greater decline in verbal fluency and executive function, while 12-month nonremitters exhibited greater decline in executive function than other groups. Conclusions Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset. This supports that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

Riddle

Potter

McQuoid

et al. 2017

The American Journal of Geriatric Psychiatry

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“…In subsequent analyses specified a priori in the ClinicalTrials.gov registration, we examined a limited number of factors that we hypothesized might moderate aripiprazole efficacy (Kaneriya et al, 2016). We found set-shifting performance, a cognitive performance measure that reflects executive function that can be assessed with the Trail-Making test, moderated aripiprazole response, while response inhibition, anxiety severity, and medical co-morbidity did not.…”

mentioning

confidence: 99%

Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder

Smagula

Wallace

Anderson

et al. 2016

Journal of Psychiatric Research

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Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n=159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size=0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size=0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo.

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“…The article by Kaneriya and colleagues 1 in this issue of JAMA Psychiatry reports on a randomized double-blind clinical trial examining the moderating factors that influence remission with aripiprazole treatment in an elderly population of participants with treatment-resistant late-life depression. The participants initially received extended-release venlafaxine hydrochloride to establish treatment resistance, and then they were randomly assigned to 12 weeks of augmentation with aripiprazole or placebo.…”

mentioning

confidence: 99%

Moderators of Remission in Patients With Late-Life Depression

Taylor

2016

JAMA Psychiatry

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Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression

Cited by 50 publications

References 28 publications

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder

Moderators of Remission in Patients With Late-Life Depression

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