David* has lived with depression on and off since he was 19. At times over the past 15 years it has arrived without warning, whereas other episodes have been triggered by a stressful event.
Having tried various treatments, including counselling and medication, all with some degree of success, he enrolled in the trial of a promising new therapy that combines gentle brain stimulation using weak electric current and thinking exercises.
During his 15 sessions over three weeks last year David found his mood unchanged, but about a month later noticed he was feeling good.
"Then in June and July I had quite a few stressful situations and in the past I probably would've fallen into a heap. However, I found I had this new resilience to get through them, which was really surprising," he says.
David wasn't the only one who was surprised. Dr Rebecca Segrave, the neuropsycologist and researcher who came up with the idea to combine gentle brain stimulation with brain training, was so shocked by the trial's results she re-checked her figures several times.
But the results were real, and she could see improvements in her patients.
"It's really thrilling to sit with someone, one on one, and hear how their life has improved," she says.
In a pilot study of about 30 participants, almost half who received the combined therapy - rather than a single treatment or a placebo -improved, and about a third were in remission by their three-week follow-up.
"That means their symptoms of depression had gone completely," Segrave says.
About one in six people will experience depression at some point in their lifetime, and of those almost 30 per cent will not respond to standard treatment such as medication, counselling and cognitive behaviour therapy.
Psychiatry professor Paul Fitzgerald says life for these patients can be very disabled. And they have high rates of suicide.
"For many years we have been hopeful that the pharmaceutical industry would come up with solutions, that there would be new drugs that would be better than the ones we already have," Fitzgerald, who works with Segrave at the Monash Alfred Psychiatry Research Centre, says.
"But many drug companies are choosing not to invest in new drug treatments for depression, so we really need other approaches," he says.
The brain training part of Segrave's encouraging new treatment works by exercising a specific brain region known as the dorsolateral prefrontal cortex. This smallish area at the front of the head is a critical control-centre for thoughts and emotions. In people with depression it is often under-active.
This explains why people with the condition have trouble controlling their emotions and disengaging the negative thoughts swirling through their mind, Segrave says.
"The area that would normally regulate that and put the brakes on is the dorsolateral prefrontal cortex, but it's under-active, so not able to control and regulate their thoughts, particularly their negative thinking."
Much like exercising muscles makes them stronger, research has found brain training based on computer-generated thinking activities can re-activate neurons in this region, reducing the severity of depression symptoms.
To maximise its effect, Segrave combines it with a gentle form of brain stimulation, known as transcranial direct current stimulation (TDCS).
"People have gotten particularly excited about it because it's very safe, it's inexpensive and it's portable," she says.
TDCS is milder than the more familiar electroconvulsive therapy (ECT), also used to treat severe depression.
While researchers have been exploring brain stimulation using electric currents as a treatment for several mental illnesses for decades, what began as rather crude experiments have evolved into a sophisticated field.
Another technique to stimulate the brain applies magnetic coils that create electrical pulses to a small region of the brain. It has become a well-established treatment for depression.
A recent experiment at Melbourne's Alfred Hospital found transcranial magnetic stimulation could offer relief to severely depressed patients after three-days of intensive treatment.
Segrave was drawn to TDCS however because, while it has been shown to improve depression symptoms, there is also evidence it can enhance a recipient's thinking skills. Repeated sessions have other downstream effects on the brain, strengthening connections between neurons, she says.
"We apply stimulation to the same region during the training to gently pre-activate that area of the brain while the training is going on."
The study found the two techniques combined had a much greater impact on reducing patients' depression severity, with lasting effects.
Fitzgerald says the combined therapy has a lot of potential. "We're very pleased with the results," he says.
Segrave applied for money from the National Health and Medical Research Council, the country's main medical research funding agency, to run a larger trial this year. While the project received positive reviews, it was not funded.
"It was considered good science, rigorous and worthy of funding, but there's not enough money to cover all the science that's worthy of funding," she says.
She is looking for other donors, and will spend months applying for government funding again this year, because she believes in the treatment.
"I'm committed to trying to get more funding because the initial results suggest this could be an exciting new treatment for depression.
"It's expensive to test new treatments, and the NHMRC is one of the only funding bodies that can give you enough money to ask the hard questions about whether it really works."
* name withheld
