Personalising treatment in psychiatry 

When it comes to the treatment of mental health disorders, it certainly isn’t a case of the one size fits all. With treatment- resistance being common in mood disorders, there’s a growing call for a more personalised approach to treatment, which can involve using both psychotropic medications and adjunctive therapies in unison.

The TRIALS team hopes that a particular biological system could hold the answer to developing the right tool to aid in guiding this approach. 

Leading the TRIALS team in this area is Dr Adam Walker. In 2020, Dr Walker became a Dean’s Research Postdoctoral Fellow, a fellowship that has allowed Dr Walker to continue his research exploring the biological response to psychiatric medications.  

Currently, by using blood samples from a variety of clinical trials, his program is exploring the interaction between immune-inflammatory markers and psychiatric symptoms to identify relevant markers to predict treatment response. Ultimately, this program aims to collate a panel of markers that will assist in treatment selection to optimise an individual’s response to psychotropic medications.  

And the program is gaining momentum, with Dr Walker now collaborating with Dr Sophie Erhardt, a professor of neuropsychoimmunology at Karolinska Institutet in Sweden and an expert in the kynurenine pathway – a pathway thought to modulate immune-inflammatory effects. The Karolinska Institutet is the home of the Nobel Medical Assembly. 

“Inflammatory systems are really complex, and they can change quite quickly,” Dr Walker says.  

“So, the idea is that by trying to look more broadly at the inflammatory markers, for instance, we can get a better picture of what’s going on and come up with a subset of markers that might help guide treatment selection. Rather than just trying to find one marker that says, ‘you should be on this treatment’, because that approach just hasn’t really worked to date.” 

Dr Walker says mood disorders such as bipolar disorder can be quite difficult to treat, especially during depressive phases. In the case of Major Depressive Disorder, instances of treatment resistance sit high, with about 30 per cent of people being considered resistant to conventional treatments.  

“The end goal is this notion that’s touted as ‘precision psychiatry’, but it’s effectively just personalised medicine,” he says. 

“It allows you to be able to perhaps look at a biological phenotype and say, ‘you have these characteristics therefore while we’d start you on the primary pharmacotherapies like we normally would, you probably would also do well with one of these adjunctive therapies as well to help improve your initial response’.  

“What we do know is that people that do fail to respond with the first medication are less likely to respond with subsequent ones. If you can sort of get it right from the outset, you have a better chance of improving illness trajectory. 

“The ultimate goal is to help curb the length of time that people spend unwell and promote mental health. I think that a better, more targeted intervention earlier is the way to do that. But we need to find out how to target it. The end goal is developing some kind of tool or panel of diagnostic or theragnostic markers that can help us guide treatment and improve people’s lives.” 

For several years, Dr Walker has researched adjunctive treatments as a way to augment treatment response. His PhD thesis explored behavioural neuroscience and investigated an animal model of treatment resistance in depression. He also looked at the mechanisms involved in treatment resistance and novel therapies, such as the use of ketamine.  

Prior to joining TRIALS, he worked in a preclinical setting, predominantly in animal studies. Since joining TRIALS he has leveraged a lot of the clinical data on adjunctive drugs such as minocycline an antibiotic, N-acetylcysteine, an antioxidative drug, and mangosteen pericarp, a fruit rind extract. 

“Those are sort of the newer treatments that have run through clinical trials here. So, I’m working with those samples to then investigate markers associated with treatment response in those clinical trials,” he says. 

In addition to the collaboration with Dr Erhardt, Dr Walker and his team will also work in collaboration with the University of Melbourne on their MiND Study, led by Dr Dhamidhu Eratne and Prof Dennis Velakoulis. Dr Walker says as part of the study, they will be looking at a marker of cognitive decline and its association with mood disorders and neurodegenerative disorders such as dementia. 

“Now that we’ve lined up these collaborations, we’re expecting to see the data come rolling in and then we can really start to bed down the data analysis and disseminate some of those findings,” Dr Walker says. 

“We have a group of us that have been working towards these goals for a while now, the Psychiatric Biomarker Discovery Group. And now that we can meet in person, we can get together and really make some progress in this area.” 

This piece is a real world impact article that was recently published in our annual report. Read the full report here