July 6, 2014  Print

Australian medical researchers have developed a new way of using Magnetic Resonance Imaging (MRI) technology to improve the notoriously hit-and-miss prescription of antidepressant drugs.

A team at the Westmead Millennium Institute for Medical Research (WMI) in Sydney has developed a test that uses a type of MRI scanning to predict whether one of three commonly prescribed anti-depressant medications (ADM) is likely to be effective in treating a particular patient.

The findings of WMI’s Brain Dynamics Centre, published in the British Journal of Psychiatry, could result in the first useful guide to clinicians when deciding on a drug treatment for a patient suffering from Major Depressive Disorder (MDD) – a decision process which the study says is currently “no better than a coin toss”.

“The remission (success) rate for all ADMs is less than 50 per cent and, if initial medication fails, the likelihood that an alternative anti-depressant will be effective lowers further to only 20 to 30 per cent,” said Brain Dynamics Centre director and study first author, Dr Mayuresh Korgaonkar.

“This is the first predictive imaging treatment test in depression and probably in psychiatry. It has the potential to significantly improve clinical service delivery and healthcare outcomes, saving the health system substantial amounts of money.”

The WMI research is part of an international study by Sydney bio-tech company Brain Resource Limited to Predict Optimised Treatment in Depression (iSPOT-D). The $20 million iSPOT-D study is seeking to identify biomarkers that can predict outcomes from treatment with common ADMs. There is currently no clinically useful pre-treatment
measure which can guide choice of therapy in depression.

Starting in 2007, data was taken from 2016 study participants across 20 sites in five countries. Almost 250 of those had their brains imaged at Westmead, with a further 40 such tests conducted at Stanford University as a control.

Senior author of the imaging study and head of imaging research at WMI’s Brain Dynamics Centre, Professor Stuart Grieve, said the iSPOT-D imaging revealed that MDD brains are “wired” differently.

“Using functional and structural MRI we characterized and mapped key brain abnormalities that distinguish a depressed state,” he said.

“We showed that patients suffering from MDD had excessive focal grey matter loss, equivalent to someone up to 50 years older, and processed emotional tasks and cognitive tasks in an abnormal way.”

Professor Grieve, who is the Parker-Hughes Professor of Radiology at Sydney University Medical School, said MRI brain scanning can identify patients who are unlikely to respond to a particular ADM with a high degree of accuracy.

“We demonstrated that altered connectivity in pathways connecting the key emotional areas of the brain predicted with 74 per cent accuracy whether an ADM would be effective.”
Having proven the concept in principle, Professor Grieve said the team is now hoping to develop a more affordable version of the testing protocol.

The team is working with Brain Resource Limited – an ASX listed company originally spun out of the Brain Dynamics Centre at WMI - and also multinational giant GE Healthcare, to translate these measures into clinical practice.

Professor Grieve said the aim is to provide patients with an abbreviated MRI test for about $200, which compared with an estimated annual cost of depression of $8000 per person, per year, would “represent an effective allocation of health care spending”.

“It’s probably not realistic that we give everyone with depression an MRI test but we think we can design a test and deliver it to market at a price which is reasonable in the context of how much depression costs,” he said.

MDD is a leading cause of morbidity, mortality, disability and lost productivity for individuals aged between 15 and 44 years, costing Australia an estimated $12.6 billion per year. Across all OECD countries the use of ADMs almost doubled between 2000 and 2011. Australia now has the second-highest rate of ADM use in the OECD, trailing only Iceland. Dr Korgaonkar said the team at WMI now hoped commercialisation of the depression treatment test could commence within five years.

“These findings are the culmination of 20 years of research at the Brain Dynamics Centre and represent the start of personalised medicine for the treatment of depression,” he said. “We are using cutting-edge techniques to define circuits in the brain that are affected by depression. This has never been done before and I think this is going to change things for the better for patients.”