Antidepressant Initiation Among Patients With Acne: Evidence From a Large Real‐World Cohort

Acne vulgaris is a common chronic inflammatory skin disorder that can significantly impact psychosocial well-being. Prior studies demonstrate associations between acne and an increased risk of psychiatric comorbidities, including depression, anxiety, and suicidality [1, 2]. However, studies evaluating the risk of antidepressant initiation and use among those with acne are lacking. To evaluate antidepressant use, we conducted a retrospective cohort study using TriNetX on December 22, 2025. Patients aged 12–45 years at first acne diagnosis (International Classification of Diseases [ICD]-10 L70 [3], index date, within 20 years of analysis) were compared with those with benign dermatologic conditions (viral warts: B07); a sensitivity analysis used patients with benign nevi (D22) as comparator. Patients with isotretinoin use were excluded given the relationship between isotretinoin and psychiatric outcomes [1]; patients with bipolar disorder diagnoses at any time or outcomes on or before index were also excluded. The primary outcome was new antidepressant initiation, with secondary outcomes of new depression or anxiety diagnosis (ICD-10 F32, F33.0-3, F33.8-9, F34.1, F40, F41 [4]), all assessed within 1 year of index date. Secondary analyses examined treatment type (topical only vs. topical plus systemic), sex, and age (12–17, 18–25, 26–45 years). Hazard ratios (HR) and risk differences (RD) with 95% confidence intervals (CI) were calculated using TriNetX. Propensity score matching was performed for demographics, psychiatric risk factors, and comorbidities. To assess potential bias from differential healthcare utilization, we performed a negative control analysis using new antihypertensive initiation. This study was exempt from institutional board review and is reported in accordance with STROBE guidelines. After matching, 298,760 patients were included in the primary acne and viral wart cohorts, which were balanced in baseline characteristics and demographics (Table 1). Compared with controls, patients with acne had higher rates of antidepressant initiation (3.09% vs. 2.65%; RD, 0.44% [95% CI, 0.35–0.52]; HR, 1.14 [95% CI, 1.11–1.18]) and new diagnoses of depression or anxiety (4.44% vs. 3.84%; RD, 0.60% [95% CI, 0.50–0.70]; HR, 1.13 [95% CI, 1.11–1.16]). Similar patterns were seen between antidepressant classes (Table 2). Results were consistent when using benign nevi as the comparator. In the negative control analysis, there was no significant difference in antihypertensive initiation between patients with acne and matched controls. Among patients with acne, those treated with topical plus systemic therapies had greater antidepressant initiation than those receiving topical therapy alone (4.18% vs. 3.12%; RD, 1.05% [95% CI, 0.95–1.16]; HR, 1.26 [95% CI, 1.23–1.30]). Hazard ratio for antidepressant use was greater among male (HR, 1.24 [95% CI, 1.18–1.30]) than female patients (HR, 1.05 [95% CI, 1.01–1.09]), and also increased with age (ages 12–17 years: HR, 1.07 [95% CI, 1.00–1.15]; 18–25 years: HR, 1.14 [95% CI, 1.08–1.22]; 26–45 years: HR, 1.15 [95% CI, 1.11–1.20]). In this large cohort study, patients with acne had higher rates of new antidepressant initiation and depression/anxiety diagnoses compared with patients with benign skin conditions. Antidepressant initiation represents a pragmatic marker of mental health burden, reflecting symptoms severe enough to warrant intervention. Risks were highest among adults and patients receiving systemic therapy, suggesting that disease severity and psychosocial context may contribute to increased burden [5]. Negative control analysis showed no association, indicating that differential healthcare utilization does not fully account for these findings. These results extend prior literature and provide a clinically actionable measure of psychosocial burden that is relevant to routine care, particularly for adults and those requiring systemic therapy. Limitations include potential residual confounding, absence of detailed acne severity metrics, and possible outcome misclassification in electronic health records. These findings emphasize the importance of recognizing psychosocial burden and integrating mental health screening into acne care. The authors have nothing to report. John S. Barbieri has received consulting fees from Honeydew Care, Twi Biotechnology, Alosa Health, and Sanofi Pasteur for work unrelated to the present study. All other authors authors declare no conflicts of interest. The data that support the findings of this study are available from TriNetX. Restrictions apply to the availability of these data, which were used under license for this study. The authors are not permitted to share the data. Data are available to researchers directly from TriNetX upon institutional access.