Professor Michael Berk, of Deakin University, is researching a possible link between a daily aspirin and preventing depression. And what if this drug was quite possibly already in your medicine cabinet, available from the supermarket, and, just as a bonus, super-cheap? "It will cost $2 a month, and there's not much that costs you $2 a month," said Michael Berk, Alfred Deakin Professor of Psychiatry at Deakin University's School of Medicine. The drug in question is aspirin – plain old boring aspirin. The little white pill, in manufacture since 1899, is widely used as a mild painkiller, and is commonly prescribed as a "blood thinner", especially following heart attacks or strokes. Now, however, driven primarily by large-scale Australian research, it is being evaluated for a possible key role in the treatment of a bewilderingly wide range of debilitating and sometimes fatal conditions.

Asprin can be used to treat a variety of conditions. The Australian research is collected under an umbrella study called ASPREE, which is investigating aspirin's effects on various health conditions. Professor Berk's work on depression comprises just one of 15 sub-studies. ASPREE involves 16,500 Australian volunteers, all aged over 70, plus a few thousand extra in the United States. It constitutes the largest clinical trial ever conducted in this country, and one of the largest in the world. Results will be available in 2018. Miracle cure? Aspirin Credit:Rohan Thomson "This is truly a paradigm changing study," said Berk.

"It's the first primary prevention study that is able to be rolled out at a general population level. The beauty of it is that you've got one agent that has the capacity to prevent multiple inflammatory-related end-points – from heart disease, to diabetes, to bowel cancer, to osteoporosis. Professor Helen Christensen, chief scientist and director at Black Dog. Credit:blackdoginstitute.org.au Until recently the inflammation was thought to be a result of the illnesses ... Research now focuses on the theory that, at least in part, the inflammation actually causes the problems in the first place. "It's an incredibly exciting study, and I think it's fair to say that something of this magnitude in sheer size and clinical importance is a very rare occurrence, indeed." Other conditions being investigated include macular degeneration, hearing loss, Alzheimer's, bung knees, infections, and even snoring.

ASPREE was set up in 2010 by Professor John McNeil, head of the Department of Epidemiology and Preventive Medicine at Monash University. Its original funding – over $50 million – came from the National Institute on Aging and Berman Center for Outcomes and Clinical Research, both in the US. It represented the largest investment ever of American funds into Australian science. Additional money has since come from Australian sources, including the Victorian Cancer Agency, CSIRO, the National Health and Medical Research Council, and various philanthropic bodies. McNeil's main aim is to investigate whether taking regular aspirin improves quality of life for the elderly. The impetus for the study arose in 2000 when a major disagreement erupted over the advisability of taking a daily pill between two peak US medical bodies: the American Health Association (AHA) and the Food and Drug Administration (FDA). Basically, the AHA thought it was a good idea. The FDA did not. "The difficulty was that there wasn't a lot of evidence, especially in older people, that the good things about taking aspirin outweighed the bad things," explained McNeil.

"When you get to prevention in people over the age of 70 there are so many other medications that they have to be on – and there's so much of an issue with side-effects and so on – that if you're going to be giving them a drug for the rest of their lives, you really want to be aware of what it's achieving, and that it's doing more good than harm. "It became quite evident that we just didn't have that information – and for the most widely used drug in the world that's a pretty big gap." At the time, McNeil and colleagues had just completed a nationwide clinical trial of a blood pressure treatment, involving 6000 people. It became clear that Australia's medical system, with its network of GPs, patient registers and highly qualified researchers, was uniquely positioned to conduct large-scale trials. Aspirin negotiations commenced. The AHA's decision to endorse daily aspirin doses as a healthcare preventative for older people in one sense reflected (perhaps over hastily) a major change occurring in medical thought regarding the main thing that aspirin tackles: inflammation. Systemic inflammation (as distinct from the localised red swelling you get after you cut your finger) is a persistent, externally symptomless arousal of the body's immune system. It has long been associated with a large number of mostly non-communicable conditions, including chronic obstructive pulmonary disease, obesity, diabetes, cancer and neurodegenerative illnesses. As early as 2003, researchers noted that it was also common among people with depression.

Until recently the inflammation was thought to be a result of the illnesses. Over the past few years, however, that thinking has been turned on its head. Research now focuses on the theory that, at least in part, the inflammation actually causes the problems in the first place. Thus, the elegant and simple solution under investigation: reduce the inflammation, and thereby reduce the disease. "Depression is much more commonly found together with other non-communicable medical disorders, such as osteoporosis, heart disease and diabetes than one would expect by chance," said Michael Berk. "All of these disorders share elevated levels of inflammation, so it seems like there's a common risk pathway for psychiatric disorders and other non-communicable disorders. This might be at least in part driven by inflammation. "The pathway works in both directions. If you have a non-communicable problem which itself generates inflammation – auto-immune diseases, for example, or obesity – you're much more likely to develop depression.

"The other important thing is that there are many environmental risk factors associated with depression, such as poor diet, smoking, inactivity and vitamin D deficiency. All of these also drive inflammation. So not only is inflammation present in depression – it is also a risk factor for depression." Professor Berk's study, dubbed ASPREE-D, necessarily focuses on elderly people, but it is not the only recent research pointing to a role for aspirin in the treatment of mental health. In 2014, a comprehensive study led by Professor Iris Sommer from the psychiatry department of the University Medical Centre in Utrecht in the Netherlands, found that aspirin improved symptoms in patients with schizophrenia, when combined with standard antipsychotic meds. And Berk himself, along with other researchers including former Australian of the Year Professor Patrick McGorry, is conducting a second study, investigating whether aspirin and a type of statin (also an anti-inflammatory) can alleviate major depression in young people. This study, possibly in a subtle display of clinical humour, is dubbed YODA-A. Berk is quick to point out that results from these investigations are still a little way off. Until they are in and analysed (and, ideally, duplicated) there is no way of knowing whether depression can be successfully treated using a pack of pills you can grab off the shelf at Coles. Neither will it be known whether they will be a sufficient treatment on their own, or whether they will work best in combination with existing types of anti-depressants.

The ASPREE-D results, however, will potentially reveal another, truly revolutionary use for aspirin. "It might be useful as a preventative," said Berk. "This is entirely new. At present we have no primary preventative pharmaco-therapy for depression." A drug to prevent the onset of depression would be groundbreaking. A cheap, readily obtainable drug to prevent depression would be doubly so. Given the massive size of the participant population in the ASPREE-D study, the results can be expected to provide a pretty clear indication of the success or failure of Berk's hypotheses. Roughly 11 per cent of the 19,000 people involved met the clinical definitions of major depression at the start of the study. Measured against a range of previous studies, a percentage of other participants can be reasonably assumed to develop depression during the course of trial. (A 2009 study led by Dr Amy Fiske of West Virginia University's Department of Psychology found that among the depressed elderly "over half of cases represent a first onset in later life".)

The effectiveness of aspirin in mental health can thus be easily measured. If the therapy is working, some or all of those depressed at the start should be in remission at the end. And the number of new cases should be less than the percentage expected under normal circumstances. Even if, at the extreme end of the good news scale, depression has vanished from the cohort, it will still not comprise evidence strong enough to provide a recommendation to GPs. There will be follow-ups to be done, numbers to be crunched, reviews to be conducted. Nevertheless, it will be very big news indeed. "It's very unusual in the history of medicine that a single study would totally change the paradigm – but a study of this size and magnitude would go a long way to changing the thinking and practice in the area," said Berk. Among those keen to study the ASPREE-D results when they come in will be Professor Helen Christensen, Chief Scientist and Director of the Black Dog Institute at the University of NSW.

Black Dog is one of the leading organisations for the research and treatment of depression. "The early research that we did on the treatments people took to manage depression showed a percentage of people took painkillers to help," she said. "At the time we thought that this was because depression was mentally 'painful', but perhaps people found that taking painkillers (including aspirin) may actually have been helpful through some other mechanism." Christensen was quick to stress, however, that the research still had a long way to go. "The neuro-inflammation hypothesis is legitimate and quite exciting, given the potential to repurpose a commonly available and inexpensive medication," she said.

"However, it certainly needs to be tested rigorously to ensure we're not giving people false hope and also not medicating unnecessarily." It was a warning echoed by John McNeil, who stressed that no one should consider adopting daily aspirins, much less swapping them for prescribed meds. "There's a lot of evidence about the good things it does," he said. "The problem is that as people get older, their blood vessels become much more fragile, and they are more likely to bleed. That's the main side effect. ASPREE's all about weighing up whether it's worth the while of the average healthy 70-plus year-old taking this." If the studies of McNeil and Berk and the researchers conducting the other 14 ASPREE sub-studies bear fruit, the cheapness and ease of access of aspirin will represent a revolution in low cost, highly effective healthcare.

Ironically, however, aspirin's status as an out-of-patent drug has meant McNeil and his colleagues have struggled for funding to conduct their world-first clinical trial. Big Pharma has contributed not a single cent. "Amounts of money like this are just routine for the pharmaceutical industry – they would spend much more than this assessing a drug," said McNeil. "But sometimes it is equally important to focus on a treatment that is not in their remit, that they don't have interests in. Aspirin is one of these. "It's very important that the whole agenda of drug research isn't driven by commercial demand. Sometimes public interest has to step in an answer important questions like this."