The power of positive thinking has been overblown as a cultural phenomenon. The same can be said for positive psychology.

It runs the risk of ignoring the obvious: Plenty of people are going through a bad time that can’t be repaired with bromides, visualising butterflies, gratitude and deep breathing.

And many of those people don’t have the psychic resources to dig themselves out of a black hole.

However, getting on to a more positive footing – as far as how you think about yourself – is a life-saving step for people with severe depression.

Unfortunately, standard treatments such as antidepressants and mood stabilisers don’t work well enough, or in the right way, to provide a sufficient breakthrough for more than a third of patients with severe depression.

These are the people who end up in the emergency department at risk of killing themselves.

The problem is these patients are in acute psychic pain, and they believe their only option is to give up on life.

All of that changes when these suicidal thoughts are gone.

For clinicians, the question is: How to achieve that, and fast?

Multiple clinical trials have found – as we first reported in 2019  –that ketamine, the powerful anaesthetic and once-popular party drug, can rapidly cause these thoughts to vanish.

How does it work?

It’s an awkward question, because, as Harvard Medical School and everybody else readily admits: “It’s not entirely clear how ketamine works.”

As the Harvard explainer tells it: Ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons.

Glutamate then activates connections in another receptor, and this helps neurons communicate with each other along new pathways.

When will ketamine make a breakthrough from party drug to depression treatment? Photo: Getty

“Known as synaptogenesis, this process likely affects mood, thought patterns and cognition,” stated Harvard.

“Ketamine works as a treatment for depression by targeting a key chemical in the brain called glutamate. It’s also thought to affect brain cell growth and function.”

Maybe

The problem is, this fits with the widely held ‘chemical imbalance theory’ used to explain antidepressants. And that theory had problems.

In July, researchers from University College London published a potentially game-changing umbrella review of the relationship between serotonin and depression.

A drug that knocks out a horse brightens up the mood of depressed people. Photo: Getty

They found: “After decades of study, there remains no clear evidence that serotonin levels or serotonin activity are responsible for depression.”

Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work by correcting abnormally low serotonin levels.

There is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.

The review suggested “that depression is not likely caused by a chemical imbalance, and calls into question what antidepressants do”.

As the authors noted: “The popularity of the ‘chemical imbalance’ theory of depression has coincided with a huge increase in the use of antidepressants.

“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence.”

So what about ketamine?

We may not be able to say with certainty how the drugs works in the brain but a new study from the Paris Brain Institute suggests how the drug works for treatment-resistant patients.

And this is where we get back to positive thinking.

The institute has published a small study that suggests “the reason why ketamine may be so rapid and effective in its relief of severe depression is because it makes us focus more on positive information than negative information, and also makes us update our beliefs based on the positive information, according to a small study by international scientists”.

Ketamine enable depressed people to look on the bright side. Photo: Getty

The study included 56 people, 26 of whom had treatment-resistant depression (TRD) and 30 of whom were mentally healthy.

Those with TRD were given three doses of ketamine on different occasions and followed up, while the mentally healthy people were not given any ketamine.

They found that people with TRD “updated their beliefs more after good than bad news following a single ketamine infusion, while the mentally healthy people did not”.

In other words, the patients took on board a sunnier set of beliefs about the world and themselves.

Another study  goes further

This week, University of Pittsburgh published a terrific study that found: “Simple computer exercises using positive words and images designed to boost self-worth can prolong the antidepressant effects of ketamine in people with depression.”

The study, which you can read about at The Conversation, included 154 adult patients with depression.

One-third received a single infusion of ketamine and returned a day later to begin four consecutive days – about 30 to 40 minutes total each day – of novel digital exercises.

These patients were shown “repeated pairings of self-related words and images – such as the letter ‘I’ and photos of the patient – paired up repeatedly with positive cues”.

These include positive words like ‘good’, ‘sweet’ and ‘loveable’ as well as photos of strangers smiling.

Associate Professor Rebecca Price.

Corresponding author Rebecca Price, Associate Professor of Psychiatry and Psychology at Pittsburgh’s Health Sciences school, said the scientists “targeted this period of time within five days of ketamine because we expected ketamine would quickly help restore the brain’s healthy capacity to adjust and learn in response to the environment”.

The other two-thirds of patients went into one of two control groups – those who received ketamine followed by a neutral, or placebo, version of computer training, and those who received a saline infusion followed by the real training exercises.

Dr Price and colleagues found that “after just a single intravenous infusion of ketamine, patients experienced relief from depression symptoms for at least one month as long as they were assigned to the group that completed the digital exercises within the first five days”.

Compared with those in the control saline group, “both of the groups that received a ketamine infusion experienced substantial relief from depression on the first day, prior to any computer training”.

The people who got digital training in the absence of ketamine had very little relief from their depression.

The study may help answer a key question in the use of ketamine: How to keep that relief going without relying solely on repeated infusions?

“These can be burdensome and costly for patients and healthcare systems, and it is important to consider possible risks, such as the potential for drug misuse,” she said.

Australian experts impatient

In 2019, we reported that a version of ketamine – in the form of a low-dose nasal spray – was approved by the US Food and Drug Administration as a fast-acting remedy for people chronically at risk of killing themselves.

Australian researchers and psychiatrists, deeply aware that there are not enough acute hospital beds for people suffering treatment-resistant depression and suicidal ideation, said Australia should be following America’s lead, instead of waiting five years to see how things play out.

University of Sydney’s Brain and Mind Centre’s Professor Ian Hickie told the ABC: “We need to get into this early, but do it smart. Historically, we get into it late and do it dumb.”

The federal government’s health advice site largely talks about ketamine as a risky recreational drug.

We haven’t got into ketamine treatment late or dumb, and outside of research, we’re not getting into it at all.