Impact of Short Videos on Agomelatine and Pregabalin Efficacy for Illness Anxiety Disorder: A Randomized Controlled Trial

Technical Summary: Impact of Short Videos on Agomelatine and Pregabalin Efficacy for Illness Anxiety Disorder

Problem Statement
Illness Anxiety Disorder (IAD) is characterized by a persistent preoccupation with having a serious undiagnosed medical illness, leading to excessive health-related behaviors and significant economic burdens on healthcare systems. While Cognitive Behavioral Therapy (CBT) and Selective Serotonin Reuptake Inhibitors (SSRIs) are standard treatments, many patients exhibit partial response or intolerance to side effects. Furthermore, the digital age has introduced short video platforms (e.g., Douyin/TikTok) as primary sources of health information. However, the impact of "fragmented" consumption of health content versus non-health content on the clinical trajectory of IAD patients remains poorly understood. This study addresses whether the type of short video content consumed as an auxiliary intervention influences the efficacy of pharmacotherapy in IAD.

Methodology
The study was a prospective, rater-blinded, randomized controlled trial (RCT) conducted at Huainan Psychiatric Hospital between October 2025 and March 2026.

• Participants: 60 patients (aged 18–65) diagnosed with IAD according to DSM-5 criteria, with baseline Hamilton Anxiety Rating Scale (HAMA) scores ≥14. Participants were medication-naive or had undergone a 4-week washout period.
• Intervention: All participants received a standardized 4-week pharmacological regimen consisting of Agomelatine (25 mg nightly) and Pregabalin (75 mg twice daily).
• Randomization: Patients were randomly assigned (1:1) to one of two groups:
  1. Health-related Video Group: Watched 2 hours daily of curated health videos focusing on anxiety management and somatic sensation interpretation.
  2. Leisure-oriented Video Group: Watched 2 hours daily of non-medical content (e.g., gardening, cooking).
• Monitoring: Smartphone usage was strictly monitored via screen-sharing (Tencent Meeting) to ensure adherence to the assigned video content and prevent access to unrelated social media.
• Assessments: Efficacy was evaluated at baseline, 2 weeks, 4 weeks, and a 12-week follow-up using the Hamilton Anxiety Scale (HAMA), Short Health Anxiety Inventory (SHAI), and Hamilton Depression Scale (HAMD-24). Assessments were conducted by independent, blinded psychiatrists.
• Statistical Analysis: Repeated-measures ANOVA was used to analyze time, group, and time-group interaction effects.

Key Results

• Participant Flow: 55 participants (27 in the Health-related group, 28 in the Leisure-oriented group) completed the 12-week trial. Five participants discontinued, primarily due to medication-related adverse events (somnolence, gastrointestinal reactions) or perceived lack of efficacy.
• Anxiety Symptoms (HAMA): Both groups showed significant improvement over time. However, starting at week 4, the Leisure-oriented Video Group demonstrated significantly lower HAMA scores compared to the Health-related Video Group (11.04 vs. 15.75; P < 0.01). This superiority persisted through the 12-week follow-up (7.04 vs. 13.30; P < 0.01). Significant time-group interaction was observed (F = 16.37, P < 0.001).
• Health-Specific Anxiety (SHAI): Mirroring HAMA results, the Leisure-oriented group showed significantly greater reduction in health-specific anxiety at week 4 (11.43 vs. 16.50; P < 0.01) and week 12 (7.54 vs. 14.19; P < 0.01).
• Depressive Symptoms (HAMD): While both groups improved, the Leisure-oriented group showed a trend toward lower scores at week 4 and significantly lower scores at week 12 (4.46 vs. 10.04; P < 0.01).
• Adverse Events: Side effects were mild to moderate (somnolence, GI discomfort) and led to the withdrawal of three participants. No severe adverse events occurred.

Key Contributions

1. Pharmacological Validation: The study confirms that the combination of Agomelatine and Pregabalin is effective in reducing anxiety and depressive symptoms in IAD patients over a 4-week acute treatment phase.
2. Digital Intervention Differentiation: The study provides empirical evidence that the type of digital content consumed as an adjunct therapy significantly alters clinical outcomes. Contrary to the assumption that health education reduces anxiety, the study found that health-related videos were less effective than leisure-oriented videos for IAD patients.
3. Mechanistic Insight: The results suggest that for IAD patients, health-related content may inadvertently reinforce "health-related rumination" and threat-response mechanisms, whereas leisure content acts as a superior cognitive distraction, interrupting the cycle of somatic monitoring and safety-seeking behaviors.

Significance and Claims
The authors claim that this trial demonstrates that leisure-oriented mobile short videos serve as a superior auxiliary tool compared to health-related videos when combined with Agomelatine and Pregabalin for treating IAD. The study posits that the mechanism of this benefit lies in cognitive distraction: leisure videos occupy working memory with non-threatening stimuli, thereby preventing the activation of the attentional bias toward health threats that characterizes IAD.

The paper concludes that clinical practice for IAD should prioritize cognitive distraction strategies, such as leisure-oriented video consumption, as a key component of comprehensive treatment plans. The authors explicitly state that while the digital intervention is effective as an adjunct, the study design (lacking a medication-only control group) prevents the isolation of the absolute effect size of the digital intervention compared to pharmacotherapy alone. They acknowledge limitations including the single-center design, small sample size, baseline BMI differences between groups, and the lack of long-term relapse assessment beyond 12 weeks.