X owner Elon Musk recently described using small amounts of ketamine “once every other week” to manage the “chemical tides” that cause his depression. He says it’s helpful to get out of a “negative frame of mind”.

This has caused a range of reactions in the media, including on X (formerly Twitter), from strong support for Musk’s choice of treatment, to allegations he has a drug problem.

But what exactly is ketamine? And what is its role in the treatment of depression?

It was first used as an anaesthetic

Ketamine is a dissociative anaesthetic used in surgery and to relieve pain.

At certain doses, people are awake but are disconnected from their bodies. This makes it useful for paramedics, for example, who can continue to talk to injured patients while the drug blocks pain but without affecting the person’s breathing or blood flow.

Ketamine is also used to sedate animals in veterinary practice.

Ketamine is a mixture of two molecules, usually referred to a S-Ketamine and R-Ketamine.

S-Ketamine, or esketamine, is stronger than R-Ketamine and was approved in 2019 in the United States under the drug name Spravato for serious and long-term depression that has not responded to at least two other types of treatments.

Ketamine is thought to change chemicals in the brain that affect mood.
While the exact way ketamine works on the brain is not known, scientists think it changes the amount of the neurotransmitter glutamate and therefore changes symptoms of depression.

How was it developed?

Ketamine was first synthesised by chemists at the Parke Davis pharmaceutical company in Michigan in the United States as an anaesthetic. It was tested on a group of prisoners at Jackson Prison in Michigan in 1964 and found to be fast acting with few side effects.

The US Food and Drug Administration approved ketamine as a general anaesthetic in 1970. It is now on the World Health Organization’s core list of essential medicines for health systems worldwide as an anaesthetic drug.

In 1994, following patient reports of improved depression symptoms after surgery where ketamine was used as the anaesthetic, researchers began studying the effects of low doses of ketamine on depression.

The first clinical trial results were published in 2000. In the trial, seven people were given either intravenous ketamine or a salt solution over two days. Like the earlier case studies, ketamine was found to reduce symptoms of depression quickly, often within hours and the effects lasted up to seven days.

Over the past 20 years, researchers have studied the effects of ketamine on treatment resistant depression, bipolar disorder, post-traumatic sress disorder obsessive-compulsive disorder, eating disorders and for reducing substance use, with generally positive results.

One study in a community clinic providing ketamine intravenous therapy for depression and anxiety found the majority of patients reported improved depression symptoms eight weeks after starting regular treatment.

While this might sound like a lot of research, it’s not. A recent review of randomised controlled trials conducted up to April 2023 looking at the effects of ketamine for treating depression found only 49 studies involving a total of 3,299 patients worldwide. In comparison, in 2021 alone, there were 1,489 studies being conducted on cancer drugs.

Is ketamine prescribed in Australia?

Even though the research results on ketamine’s effectiveness are encouraging, scientists still don’t really know how it works. That’s why it’s not readily available from GPs in Australia as a standard depression treatment. Instead, ketamine is mostly used in specialised clinics and research centres.

However, the clinical use of ketamine is increasing. Spravato nasal spray was approved by the Australian Therapuetic Goods Administration (TGA) in 2021. It must be administered under the direct supervision of a health-care professional, usually a psychiatrist.

Spravato dosage and frequency varies for each person. People usually start with three to six doses over several weeks to see how it works, moving to fortnightly treatment as a maintenance dose. The nasal spray costs between A$600 and $900 per dose, which will significantly limit many people’s access to the drug.

Ketamine can be prescribed “off-label” by GPs in Australia who can prescribe schedule 8 drugs. This means it is up to the GP to assess the person and their medication needs. But experts in the drug recommend caution because of the lack of research into negative side-effects and longer-term effects.

What about its illicit use?

Concern about use and misuse of ketamine is heightened by highly publicised deaths connected to the drug.

Ketamine has been used as a recreational drug since the 1970s. People report it makes them feel euphoric, trance-like, floating and dreamy. However, the amounts used recreationally are typically higher than those used to treat depression.

Information about deaths due to ketamine is limited. Those that are reported are due to accidents or ketamine combined with other drugs. No deaths have been reported in treatment settings.

Reducing stigma

Depression is the third leading cause of disability worldwide and effective treatments are needed.

Seeking medical advice about treatment for depression is wiser than taking Musk’s advice on which drugs to use.

However, Musk’s public discussion of his mental health challenges and experiences of treatment has the potential to reduce stigma around depression and help-seeking for mental health conditions.

Clarification: this article previously referred to a systematic review looking at oral ketamine to treat depression. The article has been updated to instead cite a review that encompasses other routes of administration as well, such as intravenous and intranasal ketamine.

Julaine Allan, Associate Professor, Mental Health and Addiction, Rural Health Research Institute, Charles Sturt University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

We’re living longer than in previous generations, with one in eight elderly Australians now aged over 85. But the current gap between life expectancy (“lifespan”) and health-adjusted life expectancy (“healthspan”) is about ten years. This means many of us live with significant health problems in our later years.

To increase our healthspan, we need planned, structured and regular physical activity (or exercise). The World Health Organization recommends 150–300 minutes of moderate-intensity exercise – such as brisk walking, cycling and swimming – per week and muscle strengthening twice a week.

Yet few of us meet these recommendations. Only 10% meet the strength-training recommendations. Lack of time is one of the most common reasons.

Walking is cost-effective, doesn’t require any special equipment or training, and can be done with small pockets of time. Our preliminary research, published this week, shows there are ways to incorporate strength-training components into walking to improve your muscle strength and balance.

Why walking isn’t usually enough

Regular walking does not appear to work as muscle-strengthening exercise.

In contrast, exercises consisting of “eccentric” or muscle-lengthening contractions improve muscle strength, prevent muscle wasting and improve other functions such as balance and flexibility.

Typical eccentric contractions are seen, for example, when we sit on a chair slowly. The front thigh muscles lengthen with force generation.

Our research

Our previous research found body-weight-based eccentric exercise training, such as sitting down on a chair slowly, improved lower limb muscle strength and balance in healthy older adults.

We also showed walking down stairs, with the front thigh muscles undergoing eccentric contractions, increased leg muscle strength and balance in older women more than walking up stairs. When climbing stairs, the front thigh muscles undergo “concentric” contractions, with the muscles shortening.

It can be difficult to find stairs or slopes suitable for eccentric exercises. But if they could be incorporated into daily walking, lower limb muscle strength and balance function could be improved.

This is where the idea of “eccentric walking” comes into play. This means inserting lunges in conventional walking, in addition to downstairs and downhill walking.

In our new research, published in the European Journal of Applied Physiology, we investigated the effects of eccentric walking on lower limb muscle strength and balance in 11 regular walkers aged 54 to 88 years.

The intervention period was 12 weeks. It consisted of four weeks of normal walking followed by eight weeks of eccentric walking.

The number of eccentric steps in the eccentric walking period gradually increased over eight weeks from 100 to 1,000 steps (including lunges, downhill and downstairs steps). Participants took a total of 3,900 eccentric steps over the eight-week eccentric walking period while the total number of steps was the same as the previous four weeks.

We measured the thickness of the participants’ front thigh muscles, muscle strength in their knee, their balance and endurance, including how many times they could go from a sitting position to standing in 30 seconds without using their arms. We took these measurements before the study started, at four weeks, after the conventional walking period, and at four and eight weeks into the eccentric walking period.

We also tested their cognitive function using a digit symbol-substitution test at the same time points of other tests. And we asked participants to complete a questionnaire relating to their activities of daily living, such as dressing and moving around at home.

Finally, we tested participants’ blood sugar, cholesterol levels and complement component 1q (C1q) concentrations, a potential marker of sarcopenia (muscle wasting with ageing).

What did we find?

We found no significant changes in any of the outcomes in the first four weeks when participants walked conventionally.

From week four to 12, we found significant improvements in muscle strength (19%), chair-stand ability (24%), balance (45%) and a cognitive function test (21%).

Serum C1q concentration decreased by 10% after the eccentric walking intervention, indicating participants’ muscles were effectively stimulated.

The sample size of the study was small, so we need larger and more comprehensive studies to verify our findings and investigate whether eccentric walking is effective for sedentary people, older people, how the different types of eccentric exercise compare and the potential cognitive and mental health benefits.

But, in the meantime, “eccentric walking” appears to be a beneficial exercise that will extend your healthspan. It may look a bit eccentric if we insert lunges while walking on the street, but the more people do it and benefit from it, the less eccentric it will become.

Ken Nosaka, Professor of Exercise and Sports Science, Edith Cowan University

This article is republished from The Conversation under a Creative Commons license. Read the original article.