INTERNATIONALLY, there are few more controversial areas of mental health practice than the widespread prescribing of antidepressant medications. Advocates of increased treatment of depression, which has the potential to reduce suicidal behaviours and maximise personal and social function, see this as a positive sign. Critics assert that the side effects of these medications have been minimised or that they are being used for less severe disorders, where psychological therapies would be a more appropriate response.

Australia has one of the highest prescribing rates per head of population among Organisation for Economic Co-operation and Development countries. For some, this rate is evidence of the success of public awareness campaigns promoting the value of active treatments for depression and the relative ease of access to care (and affordable medications) in the Australian health care system. For others, these figures ring alarm bells and suggest that the movement to support effective psychological therapies under various national health funding schemes has been less effective than originally planned.

These academic, professional and health system debates have been based largely on differing interpretations of data derived from the registration trials for each new antidepressant compound. The limitations of such short term and selective clinical trials have long been discussed. In essence, it is very difficult to extrapolate from registration trials to gauge the likely risk–benefit ratio that will result when these medicines are used in everyday clinical practice.

As a consequence, the need for much better systems of post-registration surveillance and ongoing analyses of population-level impacts has long been recognised. To date, such systems have typically used large scale administrative level data, practitioner-based surveying of treatment practices, ad hoc practitioner-based reporting of adverse events or anecdotal or single case (eg, coronial) reporting. By contrast, data provided directly by people who are actually using the medicines are rarely examined.

In the 21st century, we now have digital tools that are capable of collecting experiences of treatments directly from patients. As part of the Australian Genetics of Depression Study, in just over 3 months, we have collected detailed first-person experiences from over 13 000 individuals who have been using commonly prescribed antidepressant medicines.

This remarkable response rate demonstrates two really important facts. First, very large numbers of Australians who live with “clinical depression” are not only keen and able to share their experiences but are also very willing to partner with this style of neurobiologically oriented research. Second, new digital (online) systems can be used to derive the type of very detailed first-person data essential for advancing our understanding of the impacts of providing antidepressant medicines in real world settings.

Early inspection of these data provides unique insights into prescribing practices in Australia. Perhaps not unexpected by practitioners, over two-thirds of people have taken more than one antidepressant compound to treat their condition, while a quarter have used four or more different compounds. Two-thirds of patients taking antidepressants are also taking another prescription medicine at the same time.

The pattern of exposure to multiple different antidepressant medicines reported here means that a very common experience is failure of the initial medicine, which may reflect failure to deliver the expected benefit or the experience of intolerable side effects. In reality, as we have no method for prior prediction of individual-level response or intolerable side effects, we expose people to trial and error — commonly resulting in a prolonged sequence of treatment choices that, in many cases, is slow to deliver significant benefits.

On the up side, our early data show that 75% of patients who take on the challenge of finding a viable antidepressant strategy do experience relief in more than one of the major symptoms of depression. These are important gains and include relief of the core features of sadness or loss of pleasure in life (75%), restored control over mood or actions (52%), improved sleep or reduced anxiety (41%) and, most importantly, reduced suicidal thoughts or actions (46%). Less than 10% of patients taking medications reported no significant benefits.

On the down side, we have found that 50% of people reported significant negative aspects including direct medication side effects (eg, nausea, headaches, drowsiness and fatigue in 46% of patients), other important adverse effects (eg, increased anxiety, agitation or sleep disturbance in 18% of patients) or increased suicidal thoughts or actions (9%). While the latter phenomenon did not occur commonly, it does indicate the need for close monitoring of the potential adverse effects of treatment.

Other interesting results have also emerged. The overwhelming majority of people taking antidepressants have discussed their mental health problems with friends (90%) or family (86%). This is an important finding, as many of the risks associated with clinical depression, and the sense of isolation that accompanies the experience, may be reduced by sharing this information with trusted others. While generally positive, it was interesting that in a significant proportion of instances (10% with friends and 20% with family members) discussion with other people was reported to be unhelpful.

What is clear from this detailed database of real world clinical experiences is that we have reached the limits of the application of our current knowledge about “clinical depression”. While the practice of making antidepressants widely available does deliver considerable benefits, many people are also forced to live with ongoing side effects. To date, we have not been able to move effectively from the general principles of treating depression to much more personalised and targeted approaches that maximise the risk–benefit ratio.

The reasons for this unsatisfactory state of affairs are clear enough. The term “clinical depression” is a broad concept and undoubtedly includes a number of different illness subtypes that may be correlated with differing biochemical, chronobiological, immunological or structural brain changes, and may respond quite differently to available medical and psychological treatments. It is unfortunate that our current clinically-based diagnostic systems do not predict either differential responses to medical therapies or the likelihood of experiencing major side effects. In addition, we just don’t have the objective tools (eg, blood tests, genetic profiles or brain scans) that would substantially assist with these key clinical tasks.

So, is there real hope for improving the lives of those receiving current antidepressant treatments? The Australian Genetics of Depression Study champions one particular approach, namely, the potential for deriving specific genetic profiles that are relevant to the better targeting of existing treatments or development of new treatment strategies. On the basis of the interim data described here, better targeting of existing treatments through individual genetic profiling prior to commencement of medicines would represent a major advance in clinical therapeutics. What is clear is that large numbers of those most affected are very keen to partner with the researchers to achieve this goal.

Professor Ian Hickie, AM, is the codirector (Health and Policy) of the University of Sydney’s Brain and Mind Centre, and is one of Australia’s first National Mental Health Commissioners.

 

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