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

• Published in: European neuropsychopharmacology 2023-09, Vol.74, p.22-29
• Main Authors: Hsu, Ju-Wei, Chen, Li-Chi, Tsai, Shih-Jen, Huang, Kai-Lin, Bai, Ya-Mei, Su, Tung-Ping, Chen, Tzeng-Ji, Chen, Mu-Hong
• Format: Article
• Language: English
• Subjects: Adolescents; Antidepressant-resistant depression; Antidepressant-responsive depression; Bipolar disorder; Young adults
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2023.04.018

•Youth with antidepressant-resistant depression had a higher risk of bipolar disorder than those with antidepressant-responsive depression.•Youth who responded poorly to both SSRIs and SNRIs exhibited the highest likelihood of developing bipolar disorder.•Treatment responses to different classes of antidepressants may affect the diagnostic progression to bipolar disorder among depressed youth. Studies have demonstrated a positive relationship between antidepressant resistance and the progression of bipolar disorder. However, the influence of antidepressant classes such as selective 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 depression 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 depression. Furthermore, the group that was additionally resistant to non-SSRIs were at the highest 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 depression. Further studies are warranted to elucidate the molecular pathomechanisms underlying the resistance to SSRIs and SNRIs and subsequent bipolar disorder.