The Briefing When antidepressants don’t work + Faith leaders' warning to PM
Jan 16, 2026
Ian Hickie, a leading expert in psychiatry and co-director at the University of Sydney's Brain and Mind Centre, dives into the complexities of antidepressant responses. He reveals that about 20% of Australians with depression don't benefit from these medications due to distinct biological drivers. Exploring genetic profiles, he emphasizes the need for personalized treatment combining genetics and symptoms. He also introduces the idea of 'circadian depression,' explaining its unique symptoms and how tracking data can lead to better care.
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Depression Is Many Conditions
- Depression is not a single condition but multiple biologically distinct types with different treatment responses.
- Genetic data from ~15,000 Australians reveal subtypes that explain why some people don't respond to standard SSRIs.
Nonresponders Show Metabolic Risks
- A subgroup of patients not only fail to respond to serotonin drugs but also develop weight and metabolic side effects.
- This suggests different biological drivers beyond the serotonin system for that group.
Circadian Patterns Define A Subtype
- The so‑called atypical depression links strongly to circadian (body clock) disturbances and evening chronotypes.
- These patients tend to oversleep, gain weight, have fatigue and seasonal patterns.