Depression is the leading cause of disability worldwide, affecting over 300m people – but less than half of them are getting effective treatment.

However big pharmaceutical group Allergan is now taking its leading drug Botox through to phase III clinical trials for major depressive disorder in women (women are almost twice as likely to suffer from depression as men).

Handle with care

Botox is a neurotoxic protein best known as a treatment for wrinkles and crow’s feet.

Tiny amounts are injected to reduce neurotransmitter release between the nerves and their associated muscles, causing them to be temporarily paralysed.

This causes wrinkles to soften and skin to appear smoother.

Cosmetic to cure

With sales of over $2.7bn in 2016, Botox has been labelled a “pipeline within a drug” as it can also be used therapeutically to control a variety of medical conditions, including involuntary muscle spasms, overactive bladder and even chronic migraine.

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But how can Botox influence mental health?

There is no denying that Botox injections to the muscles above and between the eyebrows can have an effect on mood.

Treated patients experience significant mood improvements, with a single dose able to match the effects of current antidepressants.

However, the way Botox causes its mood-lifting effect remains unclear.

The leading theory? Frowning may actually make you sad.

Smile! You’ll feel better

The facial feedback hypothesis dates back to Charles Darwin, and suggests that facial expressions can have an influence on emotional experiences.

Psychologists are interested in whether negative facial expressions can actually reinforce a negative mood, via a feedback loop to nerves within the brain.

The expression of negative emotions, like scowling and frowning, often requires the contraction of eyebrow muscles.

Paralysis of these muscles using Botox interrupts this facial feedback loop, reducing the level of nerve signalling to the brain.

As a result, less negative emotions are experienced, and mood improves.

Big challenges, big rewards

The data surrounding Botox and depression is in short supply, so it is difficult to pinpoint the mechanism behind its mood-enhancing benefits.

Clinical studies are also notoriously difficult to conduct, as results rely on the use of questionnaires to assess the drug’s effect, which can be unreliable.

Allergan will therefore have a challenging road ahead in terms of getting Botox approved for depression.

However, if the trials are successful the massive scope of the market means Allergan could add $2bn–4bn to its annual sales of the drug, and have a positive impact on the lives of millions of sufferers.