Psychological distress is a growing problem among medical students worldwide. This highlights the need for psychological interventions to focus on mental health and improve well-being in this population. This study developed an internet-based, self-help, acceptance and commitment therapy program (iACT 2.0), aiming to examine its effectiveness in reducing depression, anxiety, stress, psychological inflexibility (PI), and obsessive-compulsive symptoms (OCSs) among medical students. A total of 520 Chinese postgraduate medical students were randomly assigned to either an iACT 2.0 intervention group (n=260; six online lessons, once every 5 days) or a control condition (n=260; without intervention). Participants completed questionnaires including the 21-item Depression Anxiety Stress Scale, the revised Obsessive-Compulsive Inventory, and the Multidimensional Psychological Flexibility Inventory at the preintervention (T1), postintervention (T2), and 1-month follow-up time points (T3). No therapist support was provided during the 1-month iACT 2.0 intervention period. Data were collected via an online platform and analyzed using repeated-measures ANOVA. Participants in the intervention group demonstrated a significant decrease in depression, anxiety, stress, PI, and OCSs compared to the control group after the intervention (F=22.9-672.04, all P<.001). Specifically, the intervention group showed significant reductions in all measured outcomes from the preintervention to postintervention time point and at the 1-month follow-up (all P<.001). In contrast, no significant changes were observed in the control group over the same period (all P>.05). The groups did not differ significantly at baseline (all P>.05). Significant differences were noted at both the postintervention and follow-up time points (all P<.001). This study demonstrated that the newly developed iACT 2.0 was effective in reducing depression, anxiety, stress, PI, and OCSs. Notably, the positive effects of the intervention persisted at the 1-month follow-up. This program can offer a useful addition to existing mental illness treatment and lead to improvements in clinical and psychotherapy planning while simultaneously reducing the burden on traditional counseling and services. Chinese Clinical Trial Registry ChiCTR2300070725; https://tinyurl.com/2h75wx8n.
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