They may be one of the most prescribed medicines in the country but they may not work for every patient.
New research has found antidepressants may not be as effective when used by patients with atypical depression.
The study carried out by the University of Sydney’s Brain and Mind Centre and published in Biological Psychiatry investigated associations between atypical depression and clinical characteristics, genetic profiles, and antidepressant responses.
Atypical depression is considered a distinct clinical subtype of major depression and is characterised by mood reactivity, weight gain, and hypersomnia. It is most prevalent in women.
The study used Polygenic Risk Scores to differentiate the subtype, identifying that around 21% of the 5,000 people with depression who took part in the study met the phenotypic criteria for atypical depression.
Such cases had an earlier age of onset, greater illness severity, stronger night owl behaviour and reduced daylight exposure.
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Atypical depression was associated with poorer self-reported effectiveness of selective serotonin reuptake inhibitors (SRRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), along with additional side effects, particularly weight gain.
The study’s findings support the neurobiological and clinical validity of atypical depression, demonstrating distinct clinical and genetic risk profiles alongside differential antidepressant responses.
The study concluded that support for these patients should utilise the atypical subtype to guide treatment selection and physical health management.
University of Sydney research fellow and lead author on the study Mirim Shin told Medical Forum that when doctors are assessing patients with depression they should screen beyond mood symptoms.
“While the DSM-5 defines atypical depression by mood reactivity plus at least two of four features (weight gain, hypersomnia, leaden paralysis, rejection sensitivity), clinicians can also easily identify this subtype by the presence of weight gain and hypersomnia during depressive episodes,” she said.
“These patients often present with additional features including earlier illness onset, strong evening preference, reduced daytime light exposure, and higher rates of comorbid anxiety and substance use disorders.”
Ms Shin said if first-line antidepressants are ineffective in a patient, doctors should consider chronotherapies such as bright light therapy, sleep-wake schedule regularisation, or treatments targeting their physical health conditions.
She said it was important to proactively monitor physical health in patients with atypical depression.
“Our findings showed elevated genetic risk for metabolic and inflammatory dysfunction, including type 2 diabetes, insulin resistance, and elevated C-reactive protein,” she said.
“Asking about sleep patterns, daily light exposure and weight changes can guide treatment decisions. Addressing metabolic/inflammatory health alongside mood symptoms may improve outcomes.”
Psychiatrist Dr Kyle Hoath said atypical depression had often been undervalued in relation to needing a different approach. He said this may have contributed to patients being slower to respond to treatment.
“They may be getting repeated trials of SSRIs or SNRIs or being diagnosed with a bipolar type 2 or other comorbid disorder, and then being on much more side effect heavy treatments.”
Dr Hoath, who is also President of AMA (WA), said this study was a reminder to GPs to not negate some of those differing symptoms as being part of depression.
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