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Large Study Flags Atypical Depression That Responds Poorly to Common Antidepressants

Genetic signals tie the subtype to late-sleep chronotypes with metabolic and inflammatory risks.

Overview

  • The study of 14,897 Australians, 75% women, identified an atypical subtype in 21% marked by weight gain and hypersomnia, with higher prevalence in women.
  • People with this profile were less likely to improve on SSRIs or SNRIs and were more prone to side effects such as further weight gain and drowsiness.
  • Genetic analyses linked the subtype to a night‑owl chronotype alongside elevated metabolic, immune and inflammatory risk markers.
  • Senior clinicians note that current first‑line guidance prioritizes SSRIs while overlooking atypical presentations, calling for clinician education and more personalized care.
  • Experts recommend clinical trials of circadian‑targeted therapies such as bright light and melatonin, with drugs like agomelatine highlighted for investigation.