Magnetism proves a brain wave

A world authority on brain stimulation as a treatment for mental illness tells of his journey from sceptic to champion, and bringing a novel therapy into mainstream medicine.

Story Melissa Marino

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Professor Paul Fitzgerald was hardly alone in his scepticism about using, in effect, a magnet to realign the brain’s biochemistry to treat depression. Conventional treatments at the time – the 1990s – were based firmly on psychotherapy and drugs.

But while completing a fellowship in psychiatry research at the University of Toronto, he saw the use of transcranial magnetic stimulation (TMS) as a potentially useful research tool.

Professor Fitzgerald’s interest in TMS in research stemmed partly from his indecision as a young graduate about whether to pursue a career in research or clinical practice.

IN THE MIX

Along with more than 100 staff and graduate students from fields including psychiatry, medicine, engineering and physics, MAPrc is home to an international training program for clinicians establishing their own TMS programs.

As it has turned out, his research into TMS has led to its growing acceptance as a mainstream therapy, particularly for people resistant to depression medication. It uses a hand-held coil generating a magnetic field placed close to the scalp to stimulate electrical activity in specific regions of the brain.

On his return to Australia, Professor Fitzgerald spent two years working as a clinician and raising funds for a TMS machine, though initially this was still with a research objective: “I was focused on using TMS to study brain function more than as a therapy,” he says. “But we received funding for a machine on the basis of investigating therapy … so we felt obliged to trial it.”

So began a research program in which Professor Fitzgerald thought he’d use the TMS for therapy “on the side”, but ended with him being so encouraged by its therapeutic effect that a course was set for a career in brain stimulation – and through this, a heightened interest and acceptance of the therapy globally.

“So many people did so well in that first study that I had to pursue it,” he says. “And many of these were patients who had been very depressed for a long period of time, for whom medication or therapy had failed, and for them the treatment was life-changing.”

Domino effect

The success of that first trial bolstered interest in TMS, beginning a research domino effect that would see Professor Fitzgerald lead more than 15 clinical trials and build one of the world’s most comprehensive bodies of knowledge about the treatment.

Keen to translate his findings into the community, he also established a hospital-based private practice more than a decade ago. He has now trained clinicians from many more services to provide treatment at hospitals in his home country of Australia and worldwide.

Now, he’s an international authority on TMS and no longer uncertain of its value as a treatment, or his role as researcher or clinician. “I don’t want to be one or the other. I am both,” he says.

Professor Fitzgerald achieves this by splitting his time between his private practice and the Monash Alfred Psychiatric research centre (MAPrc), which he has run with its director, Professor Jayashri Kulkarni, and Anthony de Castella since the trio established it in 1994.

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This busy clinic and research hub, partnered by Monash University and the Alfred Hospital, combines research laboratories with consulting rooms, allowing lessons learnt from innovative studies into psychiatric illnesses to be translated quickly into practice, and insights gleaned from practice to be      fed back into research.

“The sooner we can get better options to people the better – and that’s very much driven our motivation to do decent research, but at the same time ensure the research gets translated and people are getting access to treatment,” he says.

Lifting the grey blanket

In the case of depression, TMS activates the brain’s frontal nerve cells, making them repeatedly fire, strengthening the neural pathways responsible for regulating mood.

Those frontal cells are also responsible for cognition, and Professor Fitzgerald says patients often report feeling more aware and better able to concentrate early in the course of treatment. Over a period of four to six weeks, they become more engaged and interested in life, sleeping and eating better,      and able to enjoy themselves.

“They’ll say, ‘It’s like the grey blanket lifts gradually away’,” he says. Encouragingly, TMS works for some people when nothing else does; people for whom anti-depressants are ineffective, or who can’t tolerate the side effects that can range from weight gain to sexual dysfunction, nausea, headaches, agitation, insomnia and drowsiness.

Sydney psychiatrist Dr Ted Cassidy says the absence of side effects is a key benefit of TMS. “You might fix someone’s depression with medication, but because of the side effects, their actual function continues to be impaired,” he says. “And I believe treatment has to be aimed at a functional recovery.”

Confident that TMS delivers such outcomes, Dr Cassidy has established TMS Clinics Australia and partnered with Professor Fitzgerald to provide treatment for outpatients.

His conviction is founded on first-hand experience using TMS after attending Professor Fitzgerald’s training course three years ago. Of the more than 50 patients he has treated, all had failed to respond to psychotherapy and medication – but for 80 per cent of them, TMS had a positive effect.  And one-third of those became symptom-free after the treatment course.

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“I was shocked at first, because it’s one thing to read about something in papers, but when you actually have your own patients whom you’ve treated, in some cases for years with variable responses, and then see them back to normal, it’s amazing,” he says.

In recently published data, the largest study of its kind found that of 1130 people who had taken part in Professor Fitzgerald’s TMS trials over the past decade, 67 per cent had benefited from the treatment – and for 47 per cent that benefit was overtly life-changing. It was unsuccessful        for about one-third of patients. Like anything, TMS won’t work for everyone, Professor Fitzgerald says. “But when it works, it works so well.”

Expanding applications

At MAPrc, Professor Fitzgerald is continuing trials on TMS to further refine its use and improve outcomes, as well as investigating other novel brain stimulation techniques. These include transcranial direct current stimulation (tDCS), magnetic seizure therapy as a replacement for electroconvulsive therapy, and deep brain stimulation, where electrodes are implanted into the brain to stimulate activity.

The clinical applications for TMS and other brain stimulation techniques are “relatively endless”, he says. Along with depression, studies at MAPrc include TMS for schizophrenia, bipolar disorder, autism, fibromyalgia (chronic pain), post-traumatic stress disorder, obsessive compulsive disorder and Alzheimer’s disease, as well as for cognitive enhancement and substance addiction.

Professor Paul Fitzgerald

Professor Paul Fitzgerald says the clinical applications for TMS
and other brain stimulation techniques are “relatively endless”.

While research in these areas is not as advanced as in depression, for many mental illnesses there’s promising data and evidence of patients getting better and staying well, he says. For patients with schizophrenia, for example, there are instances of dramatic improvement. “I recently saw a patient who had heard persistent voices over a decade and had tried every drug under the sun – and within a week of starting TMS, her voices had gone away,” he says.

In the meantime, Professor Fitzgerald is working to refine TMS application, with research focused on two particular areas: one, to develop measures such as brain scans or genetic profiling to predict in advance who’s going to respond to treatment; and two, developing ways of administering TMS to make it work more rapidly –  perhaps in just one week rather than four to six.

The design of the hardware could play a key role in delivering such advances. Work has begun with commercial and university partners on developing devices with integrated recording capacity that could, for example, measure brain activity and administer TMS to tailor treatment to an individual’s  needs.

I recently saw a patient who had heard persistent voices over a decade and had tried every drug under the sun – and within a week of starting TMS, her voices had gone away.

Work is also underway to miniaturise the devices for both tDCS and TMS to make them more portable for possible future use at home, in aged care facilities or remote centres.

‘Hardware developer’ is another string Professor Fitzgerald could soon be adding to a crowded career bow, which, along with clinician and researcher, also includes trainer and mentor to the many graduate students he supervises. But although he never imagined TMS would branch so far when he first encountered it, he has a simple explanation for his burgeoning job description. “I have a short attention span,” he says wryly. “So, yes, there’s a fair bit going on at the moment, but that’s a good thing … I wouldn’t want it any other way.”

CASE STUDIES: TWO OF THE BEST

"One woman, six weeks after her treatment finished, told me that, in my entire life I had one single day where I felt as good as I do now, and that was the first day of my honeymoon. She was in her fifties and before this treatment had basically been depressed all her life." - Professor Paul Fitzgerald

"I have had one patient who since 2010 was on WorkCover [state compensation], was often very dishevelled and hadn’t had a job for five years. After 30 TMS treatments she improved dramatically and is now undertaking a return-to-work program. It was a real ‘seeing is believing moment." - Dr Ted Cassidy