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.

Changes are coming into effect from February 1 about how paracetamol is sold in Australia.

This mainly affects pack sizes of paracetamol sold outside pharmacies and how paracetamol is accessed in pharmacies.

The changes, announced by Australia’s drug regulator, are in line with moves internationally to reduce the harms of liver toxicity and the risk of overdose.

However, there are no new safety concerns when paracetamol is used as directed. And children’s products are not affected.

What is paracetamol?

Paracetamol is commonly sold under brand names such as Panadol, Dymadon and Panamax. It’s used to treat mild pain and fever for short periods or can be prescribed for chronic (long-term) pain.

Millions of packs of this cheap and accessible medicine are sold in Australia every year.

Small packs (up to 20 tablets) have been available from supermarkets and other retailers such as petrol stations. Larger packs (up to 100 tablets) are only available from pharmacies.

Paracetamol is relatively safe when used as directed. However, at higher-than-recommended doses, it can cause liver toxicity. In severe cases and when left untreated, this can be lethal.

Why are the rules changing?

In 2022, we wrote about how the Therapeutic Goods Administration (TGA) was considering changes to paracetamol access because of an increase in people going to hospital with paracetamol poisoning.

An expert review it commissioned found there were about 40–50 deaths every year from paracetamol poisoning between 2007 and 2020. Between 2009–10 and 2016–17, hospital admissions for this increased (from 8,617 to 11,697), before reducing in 2019–20 (8,723). Most admissions were due to intentional self-poisonings, and about half of these were among people aged ten to 24.

After the report, the TGA consulted with the public to work out how to prevent paracetamol poisonings.

Options included reducing pack sizes, limiting how many packs could be bought at once, moving larger packs behind the pharmacy counter and restricting access by age.

Responses were mixed. Although responses supported the need to prevent poisonings, there were concerns about how changes might affect:

• people with chronic pain, especially those in regional areas, where it may be harder to access pharmacies and, therefore, larger packs
• people on limited incomes, if certain products were made prescription-only.

Although deaths from paracetamol poisoning are tragic and preventable, they are rare considering how much paracetamol Australians use. There is less than one death due to poisoning for every million packs sold.

Because of this, it was important the TGA addressed concerns about poisonings while making sure Australians still had easy access to this essential medicine.

So what’s changing?

The key changes being introduced relate to new rules about the pack sizes that can be sold outside pharmacies, and the location of products sold in pharmacies.

From February 1, packs sold in supermarkets and places other than pharmacies will reduce from a maximum 20 tablets to 16 tablets per pack. These changes bring Australia in line with other countries. These include the United Kingdom, which restricted supermarket packs to 16 tablets in 1998, and saw reductions in poisonings.

In all jurisdictions except Queensland and Western Australia, packs sold in pharmacies larger than 50 tablets will move behind the pharmacy counter and can only be sold under pharmacist supervision. In Queensland and WA, products containing more than 16 tablets will only be available from behind the pharmacy counter and sold under pharmacist supervision.

In all jurisdictions, any packs containing more than 50 tablets will need to be sold in blister packs, rather than bottles.

Several paracetamol products are not affected by these changes. These include children’s products, slow-release formulations (for example, “osteo” products), and products already behind the pharmacy counter or only available via prescription.

What else do I need to know?

These changes have been introduced to reduce the risk of poisonings from people exceeding recommended doses. The overall safety profile of paracetamol has not changed.

Paracetamol is still available from all current locations and there are no plans to make it prescription-only or remove it from supermarkets altogether. Many companies have already been updating their packaging to ensure there are no gaps in supply.

The reduction in pack sizes of paracetamol available in supermarkets means a pack of 16 tablets will now last two days instead of two-and-a-half days if taken at the maximum dose (two tablets, four times a day). Anyone in pain that does not improve after short-term use should speak to their pharmacist or GP.

For people who use paracetamol regularly for chronic pain, it is more cost-effective to continue buying larger packs from pharmacies. As larger packs (50+ tablets) need to be kept out of sight, you will need to ask at the pharmacy counter. Pharmacists know that for many people it’s appropriate to use paracetamol daily for chronic pain.

Natasa Gisev, Clinical pharmacist and Scientia Associate Professor at the National Drug and Alcohol Research Centre, UNSW Sydney and Ria Hopkins, Postdoctoral Research Fellow, National Drug and Alcohol Research Centre, UNSW Sydney

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