Comparative effectiveness of selective serotonin reuptake inhibitors versus serotonin-norepinephrine reuptake inhibitors in the risk of diagnostic conversion from unipolar depression to bipolar disorder

The potential risk of diagnostic conversion from unipolar depression to bipolar disorder with antidepressant use, particularly serotonin-norepinephrine reuptake inhibitors (SNRIs) versus selective serotonin reuptake inhibitors (SSRIs), remains debated. This study aims to investigate the relationship between SSRI and SNRI use and the risk of diagnostic conversion. We conducted a retrospective cohort study using the Korean version of the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM). The target cohort comprised patients prescribed SNRIs, while the comparator cohort included those prescribed SSRIs. The primary outcome was a new diagnosis of bipolar disorder occurring at least six months after antidepressant initiation. After propensity score adjustment, no significant difference in the risk of diagnostic conversion was observed between SSRI and SNRI users. In the distributed network analysis, SNRI use was not significantly associated with an increased risk of diagnostic conversion compared to SSRI use after both 1:1 propensity score matching (hazard ratio [HR] = 1.28, 95% confidence interval [95% CI]: 0.90–1.82; <i>I</i>² = 24.1%) and 1:2 propensity score matching (HR = 1.16, 95% CI: 0.88–1.53, <i>I</i>² = 0%). This study observed no significant difference in the risk of diagnostic conversion to bipolar disorder between SSRI and SNRI users. A multicentre retrospective cohort analysis found no significant difference in the risk of diagnostic conversion to bipolar disorder between SSRI and SNRI users.The results remained consistent across both 1:1 and 1:2 propensity score matching, minimising confounding bias.Further research incorporating individual antidepressants, polypharmacy, and prospective designs is recommended. A multicentre retrospective cohort analysis found no significant difference in the risk of diagnostic conversion to bipolar disorder between SSRI and SNRI users. The results remained consistent across both 1:1 and 1:2 propensity score matching, minimising confounding bias. Further research incorporating individual antidepressants, polypharmacy, and prospective designs is recommended.