Inner East Review

The Aussies still waiting for better treatment after 75 years

By Chris Langmead
May 24 2024 - 5:30am

Around half a million Australians live with the debilitating impact of severe mental illnesses, including schizophrenia. The health, economic and societal implications are immense, yet current medical treatments for schizophrenia are based on 75-year-old science, are not effective for enough patients and often bring intolerable side effects.

Meanwhile, Australia has a growing number of leaders across drug development, psychiatry, psychology and public health, with the combined expertise to not only address the societal issue of severe mental illness, but also to place Australia at the forefront of this field.

They are the backbone of our health system and being celebrated in National Volunteer Week

Among mental health conditions, schizophrenia remains a veritable outlier, a mental health condition maligned by inaccurate tropes in film and television and feared and misunderstood by the general public. Even the etymology of the term "schizophrenia", meaning "split mind", evokes thoughts of split personalities that do not reflect the experiences of those living with schizophrenia.

It is a complex brain disorder, whose root cause even now is not fully understood. Genetics play a role, but factors as disparate as pregnancy and birth complications, childhood trauma, migration, social isolation, and urbanicity also influence risk.

Unlike dementia, it is a disorder primarily of the young, most likely to arise between the ages of 16 and 40. However, it can equally rob people of quality of life - studies estimate that Australians with schizophrenia die 25 years earlier than the general population.

Many people will be familiar with the idea that those living with schizophrenia may experience hallucinations and delusions, possibly hearing voices or entertaining false beliefs. However, these are only part of the condition.

People living with schizophrenia may also experience social withdrawal, blunted emotions and a loss of motivation. Importantly, up to 80 per cent also experience impaired cognitive functioning, including memory and attention problems.

Forgetting to take your medication, seeing your doctor, or being unable to follow instructions in the workplace can quickly impact your ability to live normally. In many cases, it is the severity of these cognitive symptoms that is the most accurate predictor of prognosis for a patient.

In respect of treatments for people living with schizophrenia, we are thankfully beyond traumatic insulin coma and electroconvulsive shock therapies, as portrayed in Ron Howards's 2001 film A Beautiful Mind. The discovery of a new type of drug, chlorpromazine (Largactil), in 1950, was revolutionary. This medicine, now known to block overactive dopamine in the brain, was the first effective pill for those diagnosed with schizophrenia, often relieving the hallucinations and delusions associated with the condition.

Looking back almost 75 years, one would imagine that such a breakthrough should have heralded a wealth of new insights and treatment options. And yet, although there have been many newer versions of chlorpromazine, they all share the same basic mechanism: blocking dopamine.

While this helps around two-thirds of people that are hearing voices or developing false beliefs, one-third get no relief at all. Furthermore, none of the medicines currently used improve social withdrawal or impaired cognition - and in many cases can worsen these symptoms over time.

Australians living with schizophrenia are often faced with treatments that cause undesirable side effects. Picture Shutterstock
Australians living with schizophrenia are often faced with treatments that cause undesirable side effects. Picture Shutterstock

Current medicines also carry unpleasant and health-limiting side effects in their own right, including weight gain, which raises the risk of diabetes and heart disease.

Those living with schizophrenia have often and understandably grown mistrustful of a health system that has promised "wonder drugs", but delivered sub-optimal medicines with distressing side effects. The lack of success is not due to a lack of effort.

A study in 2019 reviewed over 250 clinical trials for prospective new therapies, but concluded "we cannot confidently state that any of the mechanistically novel experimental treatments covered in this review are definitely effective for the treatment of schizophrenia...". However, the notion that we would still be treating people with cancer, diabetes, obesity or heart disease with medicines effectively discovered 75 years ago should be rightly ridiculed.

Thus it is heartening to see a new medicine, known as KarXT, in late-stage clinical trials in the US for people with schizophrenia. The promising results offer hope that in the next year or two we'll see the first in a new class of medicines available for treating this illness.

Even so, this new treatment has relied on a dedicated group of scientists that recognised the therapeutic value in a drug previously trialled for Alzheimer's disease in the 1990s.

Much of the research studying how KarXT works has been performed here in Australia in the past twenty years. We are blessed with world-class psychiatrists, neuroscientists, and pharmaceutical scientists, whose expertise is underutilised in the development of new medicines.

On World Schizophrenia Awareness Day, we should let this be the start of a new era and would do well to reflect on what Australia can - and should - do for those with this most-challenging of health conditions.

  • Professor Chris Langmead is director of the Neuromedicines Discovery Centre at Monash University.