Depression is one of the most common mental health conditions in Australia and around the world. Millions of people live with ongoing sadness, low energy, sleep problems, and loss of interest in daily life.
For many, antidepressant medicines are the first treatment offered. These drugs are widely used and help many people. However, a large number of patients try one medication after another without real improvement. Until now, doctors have not fully understood why this happens so often.
A major new study from the University of Sydney’s Brain and Mind Center offers an important explanation. The research suggests that depression is not a single illness, but a group of different conditions that may need different treatments.
The study focused on identifying a specific type of depression that does not respond well to standard antidepressants. This finding could change how depression is treated in the future.
The research team studied data from nearly 15,000 Australians who had experienced depression. This made it one of the largest studies of its kind. The data came from the Australian Genetics of Depression study, which collects detailed information about symptoms, health history, and genetics.
About three quarters of the participants were women, reflecting the fact that depression is more commonly diagnosed in females.
When researchers looked closely at the data, they found that around 21 percent of participants shared a pattern of symptoms that stood out clearly from the rest. This group was identified as having what researchers call “atypical depression.”
Despite the name, this type of depression is not rare. In fact, it affects a significant number of people, many of whom struggle for years without finding the right treatment.
People in this group showed different symptoms compared to what is usually expected in depression. Instead of losing weight and sleeping less, many reported gaining weight and sleeping much more than usual during their worst depressive periods.
They often felt heavy, tired, and slow, both mentally and physically. These symptoms can deeply affect daily life, work, and relationships.
Most importantly, this group did not respond well to common antidepressants such as SSRIs and SNRIs. These drugs work by changing levels of certain brain chemicals.
For people with atypical depression, these medicines were often ineffective and more likely to cause side effects such as weight gain. This can make people feel worse, not better, and may lead them to stop treatment altogether.
The study also found that people with atypical depression were more likely to have other health problems. These included conditions related to blood sugar, inflammation, the immune system, and body weight.
There were also signs that their internal body clock, which controls sleep and daily rhythms, may not be working properly. This suggests that their depression may be driven by body-wide biological changes, not just brain chemistry.
Lead researcher Dr. Mirim Shin explained that people in this group showed higher genetic risk linked to metabolism, immunity, inflammation, and sleep timing. This means their depression may follow a different biological pathway. If this is true, it helps explain why standard treatments often fail and why side effects are more common.
Professor Ian Hickie, Co-Director of the Brain and Mind Center, said the findings highlight a serious problem in current mental health care. Many Australians, especially women, are not receiving the right treatment when they first ask for help. Instead, they may spend months or years trying medications that are unlikely to work for their specific type of depression.
This research strongly supports the idea of personalized mental health care. Rather than using the same treatments for everyone, doctors could one day choose therapies based on a person’s biology, symptoms, and overall health. This could reduce long periods of trial and error, lower the risk of side effects, and help people recover faster.
When reviewing the study’s findings, it becomes clear that depression should no longer be seen as a single disorder with a single solution.
The identification of atypical depression as a distinct subtype explains why many people do not benefit from standard antidepressants. It also points to the need for new treatment approaches that focus on sleep, metabolism, inflammation, and daily rhythms.
While more research is needed, this study marks an important step toward more accurate diagnosis and better care. By understanding the biological differences behind depression, future treatments can become more effective, kinder, and truly tailored to each individual.
If you care about mental health, please read studies about 6 foods you can eat to improve mental health, and B vitamins could help prevent depression and anxiety.
For more health information, please see recent studies about how dairy foods may influence depression risk, and results showing Omega-3 fats may help reduce depression.
The study is published in Biological Psychiatry.
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