Inverse association between hydroxychloroquine use and depressive symptoms in systemic lupus erythematosus: a single-center cross-sectional study

Hydroxychloroquine serves as a foundational medication in the treatment of systemic lupus erythematosus (SLE), exhibiting multiple roles including immune modulation and cardiovascular protection. However, current research on its effect on depressive symptoms in SLE patients remains limited and yields conflicting findings. A single-center cross-sectional study was conducted at the Nanjing First Hospital, Nanjing Medical University between November 1, 2022 and December 30, 2023. A total of 106 adult Chinese patients meeting SLE diagnostic criteria were enrolled. Severity of depressive symptoms was assessed using the Patient Health Questionnaire-9 (PHQ-9), alongside demographic, clinical, pharmacological, and laboratory data collection. Statistical analyses were performed using SPSS 27.0, incorporating univariate and multivariate linear regression analysis. A total of 53.8% of the studied SLE patients exhibited depressive symptoms. Of these, mild symptoms were present in 31.2% of the patients, and a further 22.6% were burdened with moderate-to-severe symptoms. Univariate analysis indicated that hydroxychloroquine use was associated with lower PHQ-9 scores (Z = -2.253, p = 0.024), a finding corroborated by multivariate analysis showing a significant inverse association (B = -2.095, β = -0.192, p = 0.012). Meanwhile, in contrast to the negative correlation between sleep duration and depressive symptoms (B = -0.728, β = -0.231, p = 0.004), fatigue showed a positive correlation (B = 4.589, β = 0.401, p < 0.001). No significant associations were found between PHQ-9 scores and the levels of multiple cytokines (including interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ), inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)), or daily steroid dose. This study reveals an inverse association between hydroxychloroquine and SLE-related depressive symptoms. However, whether this association implies that the use of HCQ can reduce the risk of depression or alleviate depressive symptoms in SLE patients requires verification through rigorously designed prospective cohorts.