Ketamine: Why can’t severely depressed patients access this effective treatment?

Depression is a major cause of decreased quality of life. Between six and twelve percent of all people in Norway suffer from depression at any given time.

It can even be fatal. In Norway, around 650 people take their own lives every year. Many of them are severely depressed.

Current treatment is not good enough

Today we use treatment methods that are not good enough, according to many professionals in the field.

For decades, treatment of depression has mostly involved talk therapy and antidepressants. Both require long-term treatment of the patient.

Talk therapy often takes several months to work, if at all. It takes weeks and sometimes months for antidepressant drugs to take effect, if they have any effect.

One in three patients with depression are not helped by the treatment methods offered today.

With depression comes problems coping with everyday life, low self-esteem, and a lack of interest in much of what brings joy in life.

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“Without ketamine, I probably wouldn’t be here today”

Paradigm shift

The treatment of depression may now be approaching a paradigm shift, as suggested by the title of the article Psychiatry goes psychedelic in the research journal Nature in December 2021.

Since then, even more studies have been showing that psychedelics may work to relieve depressive disorders and suicidal thoughts.

The psychedelic drug ketamine is leading the way.

The drug has been used as an anesthetic in surgery since the 1970s. Around the year 2000, some researchers accidentally discovered that the administration of a low dose of ketamine produced large and rapid effects on depression in many patients. The dose should be small enough so that the patient does not fall asleep.

It works quickly

Evidence is mounting that ketamine has an effect on depression by disrupting negative thought patterns. Most studies show an approximately 50% reduction in depressive thoughts.

A recent US study showed that ketamine worked better than electroshock therapy on patients with depression. After three weeks of treatment, 55% of patients who received ketamine experienced positive effects compared with about 41% of patients who received electroshock therapy.

Psychedelics as a treatment

Ketamine belongs to a group of chemicals called psychedelics. LSD, philocybin, mescaline, and MDMA are also psychedelics.

In the 1940s and 1950s, much research was done on the drug LSD, including for the treatment of alcoholism. The results have been promising.

In Norway, many hundreds of patients were treated with LSD at Modum Bad, a psychiatric treatment centre. But panic ensued when the drug began to spread far beyond doctors’ offices and emergency rooms in the United States. Reports of patients who had “bad trips” made people even more skeptical. Skepticism spread to Norway.

President Nixon banned the use of LSD in 1967. It has been classified as a psychedelic drug. Research on the use of psychedelics in the treatment of mental disorders has gone dormant. Only in the 2000s did it start again.

The drug also works quickly, unlike other forms of treatment.

It’s fascinating to be able to treat people who have been depressed for several months and then get better in a short time, says Ole A. Andreassen. He is a professor and neuroscientist at the University of Oslo.

Ketamine is not a dangerous drug, Andreassen says.

It is used in thousands of trades every day. But in that case he becomes completely unconscious. We administer a lower dose so that patients stay awake. In this way the drug influences thinking and reduces the negative thought patterns that maintain the depressive state. A short-term effect of a low dose of ketamine may be enough to initiate positive processes that help patients get rid of depression.

Andreassen believes that ketamine may have the potential to change our understanding of the mechanisms of mental disorders.

First public hospital

Ingmar Clausen is a psychiatrist and department head at Stfold Hospital. His team treated the first patient with ketamine in a public hospital in Norway in November 2020.

Treatment in stfold takes place in a small district psychiatric outpatient clinic in the municipality of Moss. There, therapists use ketamine “off label,” that is, outside its approved area of ​​use. They are the only public hospital in Norway to use ketamine like this.

The drug is used in combination with talk therapy.

The authorities want to wait

Several studies have demonstrated good efficacy of ketamine in the treatment of depression. However, Norwegian health authorities want to know more before considering approving the drug for treatment.

They argue that the efficacy and safety have not been sufficiently documented. Health authorities await further and better studies.

The Norwegian Institute of Public Health (FHI) has been tasked with reviewing all available and current research on ketamine from around the world.

A national problem has been entrusted to a small clinic in Moss, says Ingmar Clausen.

A national problem has been entrusted to a small clinic in Moss, says Ingmar Clausen.

Clausen says there is abundant documentation available suggesting that this treatment is something that can be pursued. But as some studies have not yet been completed, health authorities are postponing their decision. It’s a little hard to take, he says.

Patients from all over the country

Clausen argues that given a substance that works so effectively, it should be used on very sick patients with a high risk of suicide.

This point is currently under discussion, Clausen says.

Stfold Hospital’s District Psychiatric Center (DPS) accepts patients with major depression from all over the country.

But the center now has a waiting period of many months for patients with treatment-resistant depression and acute risk of suicide, Clausen says.

He believes a national problem has been left for a small clinic to tackle.

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Placebos are a problem

Andreassen, the brain researcher at the University of Oslo, believes that the large number of patients who would like to receive this treatment could create problems for research.

One problem for researchers who want to learn more about the effects of ketamine is being able to determine what is a placebo effect and what is an actual effect.

The placebo effect is a well-known human phenomenon that can sometimes help people recover from illness. It is difficult to separate the placebo effect from a direct treatment effect. Many alternative treatment methods may have primarily a placebo effect.

This phenomenon is not easy to research.

They can become missionaries

Good medical studies of drug effects should be conducted as blind studies.

Doing a blind study means that neither the patient nor the person measuring the drug’s effectiveness know who is getting the real medicine and who is getting a placebo that looks identical.

This is especially difficult to achieve with a psychedelic drug, because patients usually know whether they’re getting real medicine or a placebo, Andreassen says.

We could easily become missionaries who want to prove that this drug is effective.  That's why it's important to conduct robust scientific studies of ketamine, says Ole A. Andreassen.

We could easily become missionaries who want to prove that this drug is effective. That’s why it’s important to conduct robust scientific studies of ketamine, says Ole A. Andreassen.

Another problem is that patients who want to participate in this study don’t tend to be sceptical. Many people are convinced that they can recover from depression quickly.

And we researchers who conduct the studies are also positive and therefore motivated to find an effect. We can easily become missionaries who want to prove that this drug is effective. That’s why it’s important to conduct solid scientific studies, says Andreassen.

He believes it is imperative for authorities to enforce placebo control for all research into new drugs.

Studies are underway

Although the acute efficacy of ketamine in the treatment of depression has been demonstrated in many studies, uncertainty still exists.

Andreassen believes researchers should conduct randomized trials and use placebos to study the duration of effect of an investigational drug and the risk of side effects.

Several studies have therefore been initiated to map the efficacy and side effects of ketamine in Norway.

“But should health authorities say people shouldn’t use ketamine, because the research isn’t good enough?” asks Andreassen. Is it right for the healthcare system to stop patients from receiving ketamine when most people experience positive and rapid results?”

At a minimum, authorities should support clinical trials, Andreassen says.

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Private companies take over the treatment

The University of Oslo professor admits that he and his colleagues in this field are faced with a dilemma.

The situation is not helped by the fact that private players in the Norwegian healthcare market have embarked on ketamine treatment on a large scale.

In Oslo today you can choose between several private clinics. Anyone can give you a ketamine injection for a fee. Most clinics charge between NOK 4000-5000 per treatment, roughly between USD 370-460, not including before and after consultations.

According to Stfold Hospital, some patients need several treatments to achieve optimal effectiveness. If the desired result is achieved, four to six additional treatments are performed over a period of two to three weeks. The treatment can then be maintained.

At Stfold Hospital, patients only have to pay the deductible for the outpatient consultation, Clausen says.

I usually jokingly say that a treatment with us costs NOK 39.50 (just under USD 4), she says.

Read the Norwegian version of this article at forskning.no

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Image Source : sciencenorway.no

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