TY - JOUR
T1 - Effect of augmentation with aripiprazole or augmentation with repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine extended release/duloxetine on cognition
T2 - A comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment-resistant depression (ASCERTAIN-TRD)
AU - Guidetti, Clotilde
AU - Chaikali, Stefania
AU - Trivedi, Madhukar H.
AU - Shelton, Richard C.
AU - Iosifescu, Dan V.
AU - Thase, Michael E.
AU - Jha, Manish K.
AU - Mathew, Sanjay J.
AU - DeBattista, Charles
AU - Dokucu, Mehmet E.
AU - Brawman-Mintzer, Olga
AU - Ortiz, Jesús Manuel Hernández
AU - Currier, Glenn W.
AU - McCall, William Vaughn
AU - Modirrousta, Mandana
AU - Macaluso, Matthew
AU - Bystritsky, Alexander
AU - Vila-Rodriguez, Fidel
AU - Nelson, Erik B.
AU - Yeung, Albert S.
AU - MacGregor, Leslie C.
AU - Carmody, Thomas
AU - Fava, Maurizio
AU - Papakostas, George I.
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/12/1
Y1 - 2025/12/1
N2 - Subjective cognitive impairment is a key symptom of major depressive disorder (MDD). Improvement of cognitive function in patients with treatment-resistant depression (TRD) is an important treatment outcome. This study compared the impact of augmenting antidepressants with aripiprazole or repetitive transcranial magnetic stimulation (rTMS) versus switching to venlafaxine (or duloxetine for those not eligible to receive venlafaxine) on cognition in TRD patients. In a pre-defined secondary analysis of a multi-site, open-label trial, patients with TRD were randomly assigned to aripiprazole augmentation, rTMS augmentation, or switching to venlafaxine XR/duloxetine in 1:1:1 ratio and they were treated for 8 weeks. Cognition was assessed using the Cognitive and Physical Functioning Questionnaire (CPFQ). A mixed-effects model with repeated measures was conducted. Among the 258 randomized subjects with at least one post-baseline CPFQ assessment (aripiprazole n = 91; rTMS = 70;venlfaxine XR/duloxetine = 97), neither aripiprazole nor rTMS demonstrated significant differences compared to the venlafaxine XR/duloxetine switch group in cognitive outcome as measured by CPFQ scale (p > 0.025). The mean (SE) change in CPFQ scores from baseline to Week 8 was −8.04 (0.77) (aripiprazole augmentation) versus −6.70 (0.75) (venlafaxine XR/duloxetine switch), and − 8.81 (0.64) (rTMS augmentation) versus −6.72 (0.55) (venlafaxine XR/duloxetine switch). Hedge's g values were 0.21 for aripiprazole augmentation versus switching to venlafaxine XR/duloxetine and 0.33 for rTMS augmentation versus switching to venlafaxine XR/duloxetine. Although rTMS augmentation did not reach a statistically significant difference in subjective cognitive improvement, it showed a larger effect size compared to aripiprazole augmentation. Our findings signal that rTMS augmentation may offer a well-tolerated strategy for improving cognition in TRD.
AB - Subjective cognitive impairment is a key symptom of major depressive disorder (MDD). Improvement of cognitive function in patients with treatment-resistant depression (TRD) is an important treatment outcome. This study compared the impact of augmenting antidepressants with aripiprazole or repetitive transcranial magnetic stimulation (rTMS) versus switching to venlafaxine (or duloxetine for those not eligible to receive venlafaxine) on cognition in TRD patients. In a pre-defined secondary analysis of a multi-site, open-label trial, patients with TRD were randomly assigned to aripiprazole augmentation, rTMS augmentation, or switching to venlafaxine XR/duloxetine in 1:1:1 ratio and they were treated for 8 weeks. Cognition was assessed using the Cognitive and Physical Functioning Questionnaire (CPFQ). A mixed-effects model with repeated measures was conducted. Among the 258 randomized subjects with at least one post-baseline CPFQ assessment (aripiprazole n = 91; rTMS = 70;venlfaxine XR/duloxetine = 97), neither aripiprazole nor rTMS demonstrated significant differences compared to the venlafaxine XR/duloxetine switch group in cognitive outcome as measured by CPFQ scale (p > 0.025). The mean (SE) change in CPFQ scores from baseline to Week 8 was −8.04 (0.77) (aripiprazole augmentation) versus −6.70 (0.75) (venlafaxine XR/duloxetine switch), and − 8.81 (0.64) (rTMS augmentation) versus −6.72 (0.55) (venlafaxine XR/duloxetine switch). Hedge's g values were 0.21 for aripiprazole augmentation versus switching to venlafaxine XR/duloxetine and 0.33 for rTMS augmentation versus switching to venlafaxine XR/duloxetine. Although rTMS augmentation did not reach a statistically significant difference in subjective cognitive improvement, it showed a larger effect size compared to aripiprazole augmentation. Our findings signal that rTMS augmentation may offer a well-tolerated strategy for improving cognition in TRD.
KW - Antidepressant switch
KW - Aripiprazole
KW - CPFQ
KW - Cognition
KW - MDD
KW - Patient-reported outcome
KW - TRD
KW - rTMS
UR - https://www.scopus.com/pages/publications/105010420405
UR - https://www.scopus.com/pages/publications/105010420405#tab=citedBy
U2 - 10.1016/j.jad.2025.119836
DO - 10.1016/j.jad.2025.119836
M3 - Article
C2 - 40633778
AN - SCOPUS:105010420405
SN - 0165-0327
VL - 390
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
M1 - 119836
ER -
