One in seven Australians now take antidepressants but are they working?

Depression may not be caused by a serotonin deficiency but boy do SSRIs work. 

Depression may not be caused by serotonin deficiencies but boy do SSRIs work. 

A serotonin deficiency is not why you're depressed. In fact, it's not a chemical imbalance at all, a new study has confirmed.

The large review of past studies by scientists at the University College of London in the UK claims that since a chemical imbalance is not to blame, it "calls into question what antidepressants do".

One in seven Australian adults take antidepressants, and serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants. In 2020, Zoloft, an SSRI, became one of Australia's ten most prescribed drugs.

But experts say there's pretty convincing evidence SSRIs work, even if we don't know exactly how.

University of Sydney Professor of Psychiatry Ian Hickie said this misunderstanding around a "chemical imbalance" was due to the term becoming "a shorthand" and served our desire to describe depression as chemical.

"People were desperate to say, in the early 2000s, as they often are now, depression isn't simply psychological. It isn't simply something I can decide to do differently. It had a chemical basis. That's why I'm taking a chemical solution," he said.

Although the scientific community has understood for almost a decade that a chemical imbalance is not the cause of depression, the public still tends to hold that belief - probably promoted by drug companies, experts say.

In terms of the UCL scientists questioning whether anti-depressants work, Prof Hickie said: "The basis of developing these drugs (SSRIs) was never based on the assumption there was a serotonin deficiency. These are drugs that influence monoamines, which are serotonin, noradrenaline, and dopamine". Experts say not knowing how SSRIs work is not a reason to avoid them. We don't know exactly how general anesthetics work, for example.

SSRIs do however alter the concentration or the balance of chemicals in the brain, but this was different from saying depression was due to a chemical imbalance. Aspirin relieves pain and fever but our body doesn't lack aspirin.

"This article goes back to sort of say, biology is rubbish, psychology is the explanation. It perpetuates the myth that biological treatments don't work because the precipitant may have been psychological."

Following the publication of the UCL review, "SSRIs" started trending on Twitter, with many people telling stories about how SSRIs "saved my life".

What does cause depression?

The main cause of depression was as controversial now as it was say 40 years ago, Prof Hickie said.

Whereas there was some debate in the early 2000s about whether serotonin transporters or serotonin metabolism was different in people with depression, it did not stand up, and the scientific community moved on.

There was much more interest now in the bodily systems that keep a person well, he said. This includes a person's stress response system, their hypothalamic-pituitary axis, and their sleep-wake cycle, and the extent to which you can rewire the connections between brain cells so these systems work properly.

"And there'll be many different players and different pathways in different people," he added.

The rewiring of cell connections in the brain is more likely to be the common thread of different anti-depressants and could be done by changing serotonin, noradrenaline, or dopamine levels, or through new agents like ketamine, brain stimulation, transcranial stimulation techniques, exercise, or diet. 

Are we getting closer to understanding how SSRIs work?

Yes, Prof Hickie said. "There's more and more evidence that they actually ... do help increase brain-cell connections in these critical systems."

If you, or someone you know, needs help, please called Lifeline on 13 11 14.