The chemical imbalance theory of depression is no longer valid. The paper by Moncrieff and colleagues has caused a lot of attention. There is no evidence to support the idea that depression is caused by the loss of the brain's serotonin system.

Even if we knew this was the case, they corralled the evidence that said so.

There is no correlation between the death of the chemical imbalance theory and the effectiveness of antidepressants. The medications weren't developed on this premise The chemical imbalance theory was based on an understanding of how antidepressants worked.

How did the ‘chemical imbalance’ theory start?

The first two antidepressants were found to have positive effects on mood as side effects of their hoped for functions. Iproniazid was used as a treatment fortubercolosis.

Ipronizaid is a monoamine oxidase inhibitor, which means it stops theidase that breaks down the brain chemicals. When it was first observed, we didn't know about this.

One of the effects of Imipramine is that it allows more to stay in the brain after it's been released from the body.

If both classes of antidepressants were shown to increase brain levels of serotonin, then depression must be caused by low levels of the brain chemical.

The researchers set out to show that patients with depression had lower levels of Serotonin and its metabolites in the blood, as well as in the brain.

The so-called "replication crisis" was caused by the many studies of their era. If a study failed to demonstrate the hypothesis, it was not reported at all. Larger studies and meta-analyses made it clear that the hypothesis wasn't supported.

What’s the link between the theory and antidepressants?

A clear line was found to communicate the effectiveness of their drugs. Depression was caused by a chemical imbalance.

This coincides with the development of a new class of antidepressants, theselective Serotonin Reuptake Inhibitors, which were moreselective than the tricyclic antidepressants in targeting Serotonin reuptake.

These drugs became blockbusters, and are still widely used today despite their expired patents.

Most psychiatrists didn't believe in the chemical imbalance theory. It didn't fit with the way they saw that the drugs worked, with depression not showing improvement for four weeks after taking them.

Many medical practitioners with less advanced understanding of depression and neuroscience were happy to repeat this message to their patients. The message was effective and popular. It has been said many times.

So are antidepressants effective?

There is no evidence to support the chemical imbalance theory and the new paper by Moncrieff and colleagues reiterates that. The article has received a lot of media attention.

The study found that it undermines the effectiveness of antidepressants.

A misunderstanding of medical science is shown. It's a pragmatic field of medicine. It has been proven that a treatment works before it understands how it works.

We don't know the mechanisms of action of many commonly used medicines. Knowing how they worked gave the motivation to establish how they worked.

There is convincing evidence that the drugs are effective for depression. They are not effective for everyone, but they are more effective than placebo treatments.

The magnitude of the difference between the drugs and placebo isn't good enough to justify their use. It's a matter of opinions. Many people report benefits even though some people report no benefits or harm.

How do antidepressants work?

We don't know how antidepressants work. The brain is made of many parts. We don't know how general anaesthesia works. Few people would refuse an analgesia if they were going to have a surgery.

It is of little consequence that the mechanism of action of an anti-depressant is unknown.

Let's put the theory to rest. While we search for better treatments, we should keep trying to understand depression.

Many people with depression can be helped by eating, exercising and sleeping. It can be very useful. It is for people who struggle with depression that we need to keep trying to find better treatments.