Abstract: Abstract Background Mental health disorders, including depression, anxiety, and pain, are prevalent among ambulatory patients. Nurse-Led Education and Telehealth interventions have emerged as promising approaches to improving mental health outcomes. However, their comparative effectiveness remains unclear, particularly in Saudi Arabia. Aim This study compares the impact of Nurse-Led Education and Telehealth interventions on mental health outcomes (depression, anxiety, and pain) for ambulatory patients in Saudi Arabia. Methods A quasi-expremintal study with pre and post tests were conducted with 400 participants, who were recruited through purposive sampling and assigned to receive either Nurse-Led Education or Telehealth interventions over eight weeks. Depression, anxiety, and pain were measured using the PHQ-9, STAI, and VAS tools, respectively. Data were analyzed using descriptive statistics, independent t-tests, logistic regression, and Structural Equation Modeling (SEM), with anxiety examined as a potential mediator. Results Both the Nurse-Led Education and Telehealth Intervention groups showed significant improvements in mental health outcomes, including reductions in depression (PHQ-9), anxiety (STAI), and pain (VAS). The Nurse-Led Education group improved from 20.3 to 12.4 in PHQ-9, while the Telehealth group decreased from 21.8 to 15.2, both with p
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