Predictors of Selective Serotonin Reuptake Inhibitor-Induced Akathisia in Medication-Naïve Adolescents with First-Onset Depression: A Retrospective Cohort Study

Abstract Background This study aims to identify the factors associated with akathisia induced by selective serotonin reuptake inhibitors (SSRIs) in medication-naïve adolescents with first-onset depression. The goal is to provide evidence-based recommendations for medication selection and highlight the importance of early recognition of akathisia. Methods This retrospective cohort study included 93 adolescents (mean age 15.88 ± 1.78 years; 59% female) diagnosed with depression and initiating SSRI treatment at Ningxia Medical University General Hospital between January 2022 and January 2025. Demographic, clinical, and medication-related data were collected. Akathisia was assessed using the Barnes Akathisia Rating Scale (score ≥ 2 indicating presence). Multivariate logistic regression was performed to identify independent risk factors, and a sensitivity analysis was conducted to confirm the robustness of the results. Results Multivariate regression identified comorbid anxiety (OR 6.17, P = 0.018), severe sleep disturbances (OR 1.37, P = 0.003), and severe depressive symptoms (OR 1.12, P = 0.018) as independent predictors of SSRI-induced akathisia. No significant associations were found with age, smoking, education, or family psychiatric history. Sertraline showed the highest risk of akathisia (46.5%), followed by fluoxetine (32.6%) and escitalopram (20.9%). Conclusions We identified comorbid anxiety, greater baseline depression severity, and sleep disturbances as independent risk factors for SSRI-induced akathisia in medication-naïve adolescents with first-onset depression. Early identification and tailored interventions may reduce risk. Future research should focus on validating these predictors and exploring the underlying mechanisms of SSRI-induced akathisia. Clinical trial number : not applicable.