Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.
H Nur Eken, Crystal Spotts, Benjamin Panny, Angela Griffo, Michelle Degutis, Nicolas Cruz, Elizabeth Bell, Kevin Do-Nguyen, Meredith L Wallace, Sanjay J. Mathew, Robert H Howland, Rebecca B Price
Molecular Psychiatry November 1, 2024 DOI: 10.1038/s41380-024-02564-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of a randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 154 |
| Population | Adults ages 18-60 with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem |
| Interventions | Ketamine Automated self-association training (ASAT) |
| Dose | 0.5 mg/kg |
| Duration | 4 days of ASAT, 30-day follow-up |
| Topics | Psychedelic-assisted therapy |
| Keywords | Mental health Depression treatment Behavioral therapy |
| Citations | 1 |
| Key findings | The ketamine plus ASAT group showed more positive implicit self-associations immediately after treatment, and these changes mediated extended depression improvement at Day 30 specifically for that group. |
Abstract
In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: β = -0.201; p = 0.049). Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.
Comparable studies
Other randomized controlled trials on psychedelic-assisted therapy, most cited first.
Citations in the library
Cites 6
- EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION Depression and Anxiety March 25, 2014
- Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression Translational Psychiatry May 9, 2023
- One-Year Outcomes Following Intravenous Ketamine Plus Digital Training Among Patients with Treatment-Resistant Depression JAMA Network Open May 1, 2023
- A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial American Journal of Psychiatry September 21, 2022
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity Frontiers in Psychiatry April 25, 2022
and 1 more in the library