Towards faster treatment for major depressive disorder

Major depressive disorder is common and costly – one in seven Australians will experience depression in their lifetime. So understanding what’s going on in the brain and using that knowledge to identify new, faster-acting therapeutic strategies for treatment makes sense.

“Our job is to record the electrical activity of nerve cells, the excitable cells in the brain, by way of eavesdropping on their function,” says Professor Scott Thompson, Professor and Chair of the Department of Physiology and Professor of Psychiatry at the University of Maryland School of Medicine.

“Our research is focused on the neurobiology of depression, what goes wrong in the brain when there is a case of depression and we would like to use that knowledge to offer up ideas for better, more effective, faster acting antidepressant drug treatments,” he says.

While current antidepressants – that include SSRIs (Selective Serotonin Reuptake Inhibitors) like Prozac – are effective in two thirds of patients, they typically require four to eight weeks to work and may then still need changes to the dose.

“SSRIs inhibit the uptake process of the hormone serotonin, so it builds up to a higher concentration. SSRIs like Prozac were discovered accidentally, they were being developed for treatment of problems with blood pressure and, lo and behold, some patients reported that their mood was better.”

“But where Prozac takes six to eight weeks to work, within a matter of a few hours, depressed patients given ketamine report an improvement in their mood and in their symptoms.

“Ketamine has a rapid antidepressant action, but it comes with its own set of problems. It’s an anaesthetic so it’ll knock you out if you take too much and can have a hallucinonogenic effect because it activates cells throughout your brain.

“We came up with a class of molecules that would target particular structures limited to the brain’s ‘reward circuitry’. So, in [animal models] this ketamine is a novel candidate for a rapid antidepressant, without the side effects.”

Episode recorded: February 12, 2020.

Interviewer: Dr Andi Horvath.

Producer, audio engineer and editor: Chris Hatzis.

Co-production: Silvi Vann-Wall and Dr Andi Horvath.

Banner image: Getty Images.