As a result, in the absence of compelling new science, GSK decided two years ago to throw in the towel on depression and some other areas of neuroscience.

Others cutting neuroscience work in recent years include Merck, Sanofi, Novartis and AstraZeneca, with the latter deciding in 2010 to stop discovery work in depression even as it continued with development of TC-5214.

The commercial impact is stark. Across the industry, sales are sliding fast as popular selective serotonin re-uptake inhibitors (SSRIs) like Eli Lilly’s Prozac and GSK’s Paxil are dispensed as cheap generics and new medicines of a similar type, such as Viibryd from Forest Laboratories, fail to bridge the revenue gap.

Worldwide sales of antidepressants, which peaked at $15 billion in 2003, are now expected to fall to under $6 billion by 2016, according to Thomson Reuters Pharma projections, based on consensus forecasts from analysts.

BRAIN SCANS AND MAGIC MUSHROOMS

Brain scientists say it is time for some fresh approaches.

“What we want to do is start from understanding the illness,” says Nutt. And he and others are increasingly confident they are starting to do that.

Nutt points to work by psychiatrist Catherine Harmer at Oxford University, who published what one expert commentator called a “paradigm-changing” study in the American Journal of Psychiatry in 2009.

It showed that, counter to previous thinking, antidepressants actually start working instantly even though patients may not notice the effects for months because it takes time for small changes to build up and alter their world view.

In separate research using functional magnetic resonance imaging (fMRI) brain scans, Harmer’s team showed that activation of the amygdala - the brain’s emotional hub - is blunted by antidepressants even after the first few doses.

Since emotional disorders such as depression and anxiety are linked with hyperactivity of the amygdala, this is thought to have an almost immediate but subconscious effect on reducing patients’ negative responses.

“So now we have this new theory - and it has quite a bit of evidence now - that what antidepressants do is to change cognitive bias so that people start to see the world as a more positive place,” said Nutt.

In research published in January, Nutt and colleagues scanned the brains of people tripping on psychedelic magic mushrooms and found, counter-intuitively, that the active ingredient psilocybin does not increase but rather suppresses activity in key areas of the brain.

Because the dampening effect of just one small dose of psilocybin was rapid and similar to that prompted by other depression treatments including drugs like Prozac, as well as cognitive behavioral therapy (CBT) and deep brain stimulation, the findings suggest magic mushrooms and other psychedelics could in future also be used to treat depression.

A study out this month found that another controversial treatment - electroconvulsive or electric shock therapy - also appears to turn down overactive connections between parts of the brain that control mood and parts that control thinking and concentrating.

“We’re starting to get a new understanding of brain mechanisms - not just in terms of what drugs do, but where they do it,” said Nutt. “It’s important to see the brain as a whole, and the research benefits of that are going to be quite profound.”

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(Reuters)