Disease progression to bipolar disorder among adolescents and young adults with antidepressant-resistant and antidepressant-responsive depression: Does antidepressant class matter?

Studies have demonstrated a positive relationship between antidepressant resistance and the progression of bipolar disorder. However, the influence of antidepressant classes such as se-lective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) in this context has yet to be investigated. A total of 5,285 adolescents and young adults with antidepressant-resistant depression and 21,140 with antidepressant-responsive depression were recruited in the present study. The antidepressant-resistant depression group was divided into two subgroups: only resistant to SSRIs ( n = 2,242, 42.4%) and additionally resistant to non-SSRIs ( n = 3,043, 57.6%) groups. The status of bipolar disorder progression was monitored from the date of depression diagnosis to the end of 2011. Patients with antidepressant-resistant de-pression were more likely to develop bipolar disorder during the follow-up (hazard ratio [HR]: 2.88, 95% confidence interval [CI]: 2.67-3.09) than those with antidepressant-responsive de-pression. Furthermore, the group that was additionally resistant to non-SSRIs were at the high-est risk of bipolar disorder (HR: 3.02, 95% CI: 2.76-3.29), followed by the group that was only resistant to SSRIs (2.70, 2.44-2.98). Adolescents and young adults with antidepressant-resistant depression, especially those who responded poorly to both SSRIs and SNRIs, were at increased risk of subsequent bipolar disorder compared with those with antidepressant-responsive de-pression. Further studies are warranted to elucidate the molecular pathomechanisms underly-ing the resistance to SSRIs and SNRIs and subsequent bipolar disorder. & COPY; 2023 Elsevier B.V. and ECNP. All rights reserved.

Automated summary

Studies have shown that there is a positive relationship between resistance to antidepressants and the progression of bipolar disorder. However, the specific influence of different types of antidepressants, such as SSRIs and SNRIs, in this context has not been thoroughly investigated. This study recruited a total of 5,285 young people with antidepressant-resistant depression and 21,140 with antidepressant-responsive depression. It was found that those with resistance to antidepressants, especially to both SSRIs and SNRIs, were at an increased risk of developing bipolar disorder.