Ketamine can provide relief to patients with severe depression “where nothing has helped before”, researchers calling for a new approach to the drug’s medical use have said.
For six years, scientists from Oxford University have been using ketamine to treat more than 100 people with treatment-resistant depression.
They said patients who received a series of carefully administered intravenous infusions of the drug, followed by oral top-ups, showed sustained improvement in around 40 per cent of cases – a significant result when other antidepressants have failed.
“There are lots of people who are currently resistant to antidepressant drugs and psychotherapies,” consultant psychiatrist Rupert McShane told The Independent.
“We’d like to see some more centres developing expertise [about ketamine] and starting to use it.”
One patient who took part in the trials said ketamine had slowed down the “constant, overwhelming bombardment of negative intrusive thoughts surging through your brain” and given her the opportunity to “fight back”.
Dr McShane, who led Oxford’s ketamine treatment programme, said the only other treatment for severe depresson with a higher success rate that ketamine was electroconvulsive therapy (ECT), which was at around 70 per cent.
“A lot of people would never want to have ECT, largely because of stigma. It’s an underused treatment, without a doubt,” he said.
Ketamine, which was discovered in 1962, is licenced for medical use as an anaesthetic but is also used illegally as a recreational drug.
Trials into its use as a treatment for depression are in early stages, said Dr McShane, who is calling for a new medical registry to track where and how it is prescribed and provide a “layer of scrutiny that currently we don’t have for any antidepressants”.
It is estimated around three per cent of the UK population, or nearly two million people, suffer from depression.
A small proportion of this group – around 158,000 people in total – have very severe depression that is resistant to existing treatments, studies have shown.
Depression “isn’t a disorder of underactivity of the brain, it’s a disorder of overactivity”, said Dr McShane.
“In people who are depressed there’s an excessive connectedness between the emotional regulation area and other areas of the brain.”
Both ketamine and ECT appear to reduce this hyperconnectivity, he said, as well as increasing levels of a chemical produced in the blood that helps new synapses to form in the brain.
The majority of 101 patients who received the treatment in Oxford, around 70 per cent, saw some improvement in their condition after one 40-minute intravenous infusion of ketamine.
They were then offered two more infusion sessions, followed by oral ketamine given twice weekly and the possibility of further ‘top-up’ infusions, to allow the scientists to calculate the overall response rate of the drug over time.
“When people are having an infusion, during that period they feel very peculiar. That dissociation is sometimes more powerful than people think it’s going to be,” said Dr McShane.
“Over the course of the three infusions, sometimes people don’t feel anything until the second infusion, sometimes the dose needs to be increased in the third. But sometimes people will start to feel better the following morning after the first.”
Louise, a 36-year-old former nurse who took part in the trial, said: “In depression and anorexia you get a constant, overwhelming bombardment of negative intrusive thoughts surging through your brain. You are just instantly paralysed and snowed under: you don't stand a chance.
“Ketamine slows this down so you can fight back. I’m the most stable I've been in years and have hardly spent any time in hospital compared to before ketamine.
“I definitely do not feel at all, in any way ‘hooked on’ or addicted to the ketamine. I have more trouble with withdrawal and side effects if I miss a couple of doses of my [standard] antidepressant than I do with the ketamine.”
And David, a 64-year-old with bipolar disorder, said the treatment had allowed him to “live for a few days a week rather than just exist”.
Dr McShane’s colleague Ilina Singh is the lead author on a new paper, published in The Lancet, which outlines the team’s recommendations for ethical and effective trials into the treatment, based on their experiences.
“Our approach balances the potential harms of ketamine use for treatment-resistant depression, such as its misuse potential, with a focus on reporting structures that promote the broad benefits of clinical innovation and the ethical judgement of the clinician,” said Professor Singh.
Dr McShane said patients had been cautious of the treatment because of ketamine’s reputation as a party drug, but emphasised it was “one of the safest anaesthetics there is”.
He said he and his team had encountered cases of people buying ketamine illegally to self-treat their condition, but this “sometimes escalates out of control,” with people experiencing side effects such as bladder problems and anxiety.
One of the 101 patients reported a possible bladder complaint, which improved after they stopped treatment, and there were some reports of poor memory and five people stopped after one infusion because the felt faint.
Allan Young, of the Royal College of Psychiatrists, said preliminary data suggested ketamine “may be a safe and effective treatment for severe depression and suicidal feelings” but advised mental health practitioners to proceed with caution before treating patients with the drug.
“Despite clinical trials showing rapid improvement in mood after ketamine infusion, there are still significant gaps in our knowledge about dosage levels, treatment protocols and the effectiveness and safety of long term use,” he said.
“Before ketamine can be recommended for use in clinical practice, extensive research is required to understand how to optimally use ketamine for treating depression.”
Michael Bloomfield, clinical lecturer in general psychiatry at University College London, expressed his support for the creation of a centralised registry to better understand the use of ketamine as a treatment for depression.
“More research is needed and having a registry allows researchers to share new findings, positive or negative. For example, one challenge is to determine how to prolong any positive effects, perhaps through multiple dosing, or by adding other drugs,” he said.
“Also, to bring its use from lab to clinic, more acceptable and practical modes of administration might be equally effective. Finally, ketamine might be used more routinely in non-treatment-resistant depression, to accelerate improvement in combination with more conventional antidepressants."