Background: Major Depressive Disorder (MDD) affects approximately 300 million people worldwide. Despite available treatments, many patients do not achieve full recovery with traditional antidepressants, and others lack access to evidence-based care. Esketamine, a glutamatergic agent approved for treatment-resistant depression, and mindfulness meditation represent promising approaches for depression care that may improve neuroplasticity. The neuroplasticity theory of depression posits that reduced neural plasticity contributes to MDD development, with both esketamine and mindfulness potentially addressing this deficit.
Objectives: This quality improvement project aimed to implement and evaluate the feasibility and efficacy of adding mindfulness meditation to esketamine treatments for patients with MDD, with the goal of improving depression outcomes.
Methods: A quasi-experimental pilot was conducted at an outpatient psychiatric clinic with 19 participants (10 in mindfulness plus esketamine group, 9 in usual care esketamine-only group). Outcome measures included changes in depressive symptoms using the Patient Health Questionnaire-8 (PHQ-8), mindfulness domains of self-compassion and acting mindfully using Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF) subscales, and Hope, Agency, and Opportunity (HAO) scores. The intervention consisted of structured mindfulness meditations during esketamine treatments. Data were analyzed using t-tests, regression modeling, and Pearson’s r correlations.
Results: Patients receiving the mindfulness adjunct had significantly greater PHQ-8 score reductions (4.70 points) compared to the usual care group (1.00 point; p = .014), with a large effect size (Cohen’s d = 1.27). Within the mindfulness group, self-compassion scores significantly increased (p < .01) and were strongly correlated with PHQ-8 score improvements (r = -0.71, p = .032). Both groups showed excellent treatment adherence. All mindfulness group participants reported satisfaction with the intervention.
Conclusion: Adding mindfulness meditations to esketamine treatments provided clinically meaningful improvements in depressive symptoms compared to esketamine alone. The strong correlation between increased self-compassion and depression symptom reduction highlights a potential mechanism for this effect. This feasible, well-received intervention offers a promising approach to enhance outcomes for patients with MDD undergoing esketamine treatment. Future research should examine optimal timing, duration, and long-term benefits of this integrative approach.
