22nd November 2021
By Emily Ledger
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Depression is one of the most common mental health conditions and the leading cause of disability worldwide. It is estimated that between 4 and 10% of adults in the UK will experience depression at some point in their lives. The high occurrence of depression makes the ongoing search for effective treatment options more important than ever – and some people believe that ketamine could help…

While there are a number of treatment options available for depression, these can often take weeks or even months to take effect. Many people may also have to try several therapies before finding an effective solution. The rapid action of ketamine means that it could be useful as an alternative or adjunctive therapy for treatment-resistant depression.

There are a number of treatment options available for depression, however, their efficacy can vary depending on a number of factors. For some people, current therapies may have all proved ineffective – this is called treatment-resistant depression.

What is Ketamine?

Ketamine was first synthesised in the 1960s and started out as an anaesthetic medicine for animals. It began to be used as an anaesthetic for humans in 19070 and was used in treating injured soldiers in the Vietnam War.

Ketamine is also used illegally as a recreational drug. It is a dissociative drug that can cause visual and auditory distortion and a detachment from reality.

In recent years, a number of studies have assessed the potential of ketamine as a treatment for depression. Two main types of ketamine that can be used to treat major depression that hasn’t improved with other therapies (treatment-resistant depression):

Racemic ketamine – sometimes called intravenous, or IV, ketamine as it is delivered straight into the bloodstream, contains both “R” and “S” ketamine molecules. The product was approved as an anaesthetic decades ago, however, it remains unlicensed for the treatment of depression.

Esketamine (Spravato) – was approved by the FDA in the US as a depression treatment in 2019. It is a nasal spray that only contains the “S” ketamine molecule.

How does ketamine help treat depression?

It is still not exactly clear how ketamine works as an anti-depressant, but it is believed to act through a different mechanism to other depression treatments. This means that ketamine could be an effective alternative treatment when other therapies have been unsuccessful.

Researchers believe that ketamine is able to help neurons connect with each other through new pathways – a process called synaptogenesis which likely affects cognition, mood, and thought patterns – all of which could potentially have an impact on depression.

Ketamine likely binds to NMDA receptors in the brain, leading to an increase in a neurotransmitter called glutamate. This molecule then activates another receptor – the AMPA receptor – which plays an important role in synaptogenesis.

However, current research shows that ketamine may also impact depression through other pathways. For example, ketamine may reduce signals that trigger inflammation, which has been linked to some mood disorders.

What is the Evidence?

A recent review (2019) assessed the existing evidence for the use of ketamine for the treatment of depression. The researchers identified a number of studies – in which ketamine was measured either against placebo or comparators – that supported the potential of ketamine for this indication.

In 14 trials, “provided a rapid antidepressant effect with a maximum efficacy reached at 24 hours.” The researchers concluded that ketamine’s rapid onset could make it a useful adjunctive/alternative treatment in depressed patients with suicidal ideation.

ketamine depression psychotherapy
Patient speaking with a psychologist during a therapy session.

Ongoing research into ketamine for depression

Over the last few years, research into the anti-depressant potential of ketamine has picked up pace as part of a wider wave of psychedelics research.

For example, the Canadian government recently announced that it would be funding a first-of-its-kind study into the potential of ketamine treatment in people with bipolar depression.

Ketamine-assisted psychotherapy is also becoming gaining a lot of attention. It involves the use of ketamine alongside a professional therapy session with a psychologist. The aim of ketamine-assisted psychotherapy is to confront potential triggers and causes for depression while using ketamine to help build new brain connections and neural pathways.

While the evidence looks promising, and researchers are increasingly interested in the potential of ketamine, there is still a long way to go to gather the evidence needed to make this new therapy a mainstream option for those living with depression.

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