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Ketamine research reports 75pc success rate in treatment of long-term depression
The dissociation seen with ketamine is a trance-like cataleptic state, ie the patient has their eyes open but doesn’t respond. As patients wake up from this, they go through a confusional state somewhere between unconscious and fully conscious, known as ‘emergence phenomenon’. This can be utterly terrifying with vivid hallucinations of sound, sight and smell. A patient who was given ketamine whilst agitated or scared will wake up with those same feelings now magnified, hence the problems we see in ED. Sometimes the patient settles with constant and repeated reassurance – a time consuming and challenging job. Sometimes they become so agitated they require sedation with benzos – which makes their assessment near impossible until it wears off after several hours. As we’re then unable to examine these patients, we often have to do CT pan-scans to diagnose them – a significant amount of unnecessary radiation for the patient, not to mention work, time and expense for the hospital. In extreme cases the emergency phenomena is so bad patients require paralysis and intubation for their own safety – a massive escalation of events from their pre-hospital treatment. This happened recently in a guy given pre-hospital ketamine analgesia (>80mg) for a hand injury – instead of getting stitches and follow-up with Ortho he ended up on a ventilator in ICU. This is why many ED nurses and doctors are less than delighted to hear a patient has been given ketamine – it often adds layers of complexity onto what could have been a simple case.
Before we go further, time for a quick revision of how ketamine works:NMDA receptor antagonist = analgesia, amnesia, anaesthesia, sedationInteracts with opioid receptors = increases effects of opioidsMuscarinic receptor antagonist = bronchodilatation, mild tachycardia and hypertensionProvides quick onset as it rapidly crosses the blood-brain barrier, so peak effects seen around 1minute after IV bolus, 5mins after IM.Duration of action up to 15mins IV, 25mins IMAdverse effects: vomiting, emergence reaction (hallucinations), salivationSo what’s this dissociation malarkey everyone talks about?The dissociation seen with ketamine is a trance-like cataleptic state, ie the patient has their eyes open but doesn’t respond. As patients wake up from this, they go through a confusional state somewhere between unconscious and fully conscious, known as ‘emergence phenomenon’. This can be utterly terrifying with vivid hallucinations of sound, sight and smell. A patient who was given ketamine whilst agitated or scared will wake up with those same feelings now magnified, hence the problems we see in ED. Sometimes the patient settles with constant and repeated reassurance – a time consuming and challenging job. Sometimes they become so agitated they require sedation with benzos – which makes their assessment near impossible until it wears off after several hours. As we’re then unable to examine these patients, we often have to do CT pan-scans to diagnose them – a significant amount of unnecessary radiation for the patient, not to mention work, time and expense for the hospital. In extreme cases the emergency phenomena is so bad patients require paralysis and intubation for their own safety – a massive escalation of events from their pre-hospital treatment. This happened recently in a guy given pre-hospital ketamine analgesia (>80mg) for a hand injury – instead of getting stitches and follow-up with Ortho he ended up on a ventilator in ICU. This is why many ED nurses and doctors are less than delighted to hear a patient has been given ketamine – it often adds layers of complexity onto what could have been a simple case.
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Elon Musk says ketamine can get you out of a 'negative frame of mind'. What does the research say?
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 Musk-owned X (formerly Twitter), from strong support for Musk's choice of treatment, to allegations he has a drug problem.
Jim Cramer on @elonmusk’s Ketamine use: “Here’s a man who admits he had depression, admits that he’s taking a drug that had helped million of people, and for that he’s pilloried? There are many people who would never be brave enough to admit that they take this drug.” pic.twitter.com/ge6I5gKtzE
— Sawyer Merritt (@SawyerMerritt) March 19, 2024But 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.
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