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Set-shifting performance indicates aripiprazole response in treatment-resistant depression

Set-shifting performance predicted response to aripiprazole augmentation among older adults with treatment-resistant depression, according to recent findings.

“Over half of older adults with major depressive disorder fail to respond adequately to first-line pharmacotherapy with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors,” Shriya H. Kaneriya, BA, of University of Pittsburgh School of Medicine, and colleagues wrote. “Persistent depression in this population heightens the risk for disability, nonadherence to treatment of other medical disorders, cognitive impairment leading to dementia, low quality of life, caregiver burden, suicidality and early mortality. Data from randomized controlled clinical trials to guide second-line treatment for older adults are sparse.”

To determine the moderating role of pretreatment executive function, severity of anxiety and severity of medical comorbidity in remission of treatment-resistant late-life depression following aripiprazole augmentation, researchers conducted follow-up to a 12-week randomized clinical trial of aripiprazole augmentation for first-line, treatment-resistant late-life depression. Adults aged 60 years and older whose major depression failed to remit with venlafaxine hydrochloride monotherapy received aripiprazole (n = 91) or placebo (n = 90). Treatment started at 2 mg daily and titrated as tolerated to a maximum dose of 15 mg daily.

Remission occurred among 43% of the aripiprazole group and 29% of the placebo group.

Baseline set-shifting moderated efficacy of aripiprazole augmentation (OR = 1.66; 95% CI, 1.05-2.62; P = .03).

Among participants with a Trail Making Test scaled score of 7 or more, odds for remission were significantly higher among those who received aripiprazole than placebo (53% vs. 28%; OR = 4.11; 95% CI, 1.83-9.2).

Aripiprazole and placebo were equally effective among participants with a Trail Making Test scaled score lower than 7 (OR = 0.64; 95% CI, 0.15-2.8).

Greater anxiety severity at baseline predicted a lower remission rate but did not moderate aripiprazole efficacy. Each standard deviation of greater baseline anxiety severity was associated with 50% lower odds for remission among both treatment groups.

Medical comorbidity and performance on Color-Word Interference test did not predict or moderate treatment efficacy.

“Our study extends published observations of executive impairment, anxiety and medical burden as correlates or predictors of poorer outcomes in late-life depression. Our findings support set-shifting performance as a moderator of short-term remission (ie, influencing the efficacy of aripiprazole) and distinguish anxiety as a general short-term prognostic variable (predictor),” the researchers wrote. “Further examining a wider range of pretreatment factors, including other aspects of cognition, as well as the neurobiological basis of these observed effects, will continue to improve our understanding of how treatments work and for whom they do or do not work.” – by Amanda Oldt

Disclosure: Kaneriya reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.