The effect of sertraline on networks of mood and anxiety symptoms: secondary analysis of the PANDA randomized controlled trial

Journal article

Depression consists of heterogeneous symptoms that can occur in hundreds of possible combinations. However, intervention studies commonly operationalize depression as a homogeneous condition. Here we adopt a symptom-level approach to test the effects of the selective serotonin reuptake inhibitor sertraline on depression and anxiety symptoms and to test their associations. Using data from the PANDA randomized controlled trial, we use network models to estimate the effects of sertraline at different time points (contemporaneous networks at 2, 6 and 12 weeks) and across time (temporally lagged networks). Results show that sertraline has beneficial effects on core depression and anxiety symptoms as early as after 2 weeks of treatment, counteracted by detrimental effects on somatic symptoms of depression. This intricate pattern of treatment effects is typically masked when measuring depression on a single dimension. Focusing on individual symptoms of depression and anxiety may shed light on the nature, effectiveness and timing of antidepressant action.

Authors: Piazza, GG; Allegrini, AG; Duffy, L; Lewis, G; Roiser, JP

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: nature mental health
• Volume: 3
• Issue: 11
• Pages: 1417-1424
• Publication date: 2025-10-30
• DOI: 10.1038/s44220-025-00528-x
• EISSN: 2731-6076
• ISSN: 2731-6076
• Language: English
• Keywords: Serotonin reuptake inhibitor; Randomized controlled trial; Depression (economics); Antidepressant; Sertraline; Mood; Anxiety