Experts back ketamine for depression, but call for more research on other drugs

The Royal College of Psychiatrists (RCPsych) has backed the use of ketamine-based medication to treat people with depression in clinical settings, but stressed that further research is needed on other psychedelic drugs.

Experts said it is “vital” that new treatments for mental health conditions are developed, but there is a risk of claims around psychedelics “jumping ahead of the evidence” and the “hype” should not be “prioritised above good clinical practice”.

RCPsych laid out its stance on psychedelic and related substances for medical use, which include pharmacological versions of hallucinogens, ketamine and methylenedioxymethamphetamine (MDMA), in a new position statement.

It said ketamine has been “the most studied in the rapid relief of depressive symptoms with evidence of efficacy including large randomised controlled trials”.

According to the statement, ketamine has been used in studies involving thousands of patients to explore the impact on depression.

There are also ongoing and completed trials looking at how it affects people with obsessive-compulsive disorder, post-traumatic stress disorder (PTSD) and alcohol or cocaine abuse.

A drug derived from ketamine – a nasal spray known as esketamine – is licensed in the UK for treatment-resistant depression.

It is available on the NHS in Scotland but not in England.

RCPsych said it would “recommend the use of ketamine in specialist settings with appropriate oversight and long-term monitoring arrangements”.

However, it added that while early clinical studies of other psychedelics have been “encouraging”, there is “concern around the difficulties in conducting adequately blinded trials, as well as regarding side effects and whether any therapeutic benefits observed are sustained over time”.

“These factors combined with questions regarding validity amongst clinical populations mean the current evidence base is limited, and it is not recommended that they are used in routine clinical practice other than where licensed,” the college said.

Professor Oliver Howes, chairman of RCPsych’s psychopharmacology committee, said: “New treatments are very rarely developed for mental illnesses and disorders… it’s vital that that trend is reversed.

“We did some work in the last 10 years – on average, we get just one new treatment for mental disorders licensed and available for our patients, and that compares to four times as many in neurology and over 10 times as many in cancer. So there is a real gap there.”

Prof Howes added: “Why do we need new treatments for mental disorders?

“Well, we have effective treatments, but we know that for a fair proportion of patients, they either don’t work, or they’re not well tolerated, they get side effects, or they take a long time to work.”

He said there is a “huge amount of interest” in psychedelics and there is “a risk of claims jumping ahead of the evidence”.

The college said new findings are likely to emerge in the coming years and its position will require updating.

The Australian government legislated for MDMA and psilocybin – a naturally occurring psychedelic compound found in certain mushrooms – to be prescribed for clinical use by approved psychiatrists from July 2023.

Canada and Israel also have pathways to allow the use of psychedelics compassionately, the statement said.

Studies are looking at use of LSD to treat substance abuse, anxiety and depression, ketamine-assisted psychotherapy for alcohol dependence, and MDMA-assisted psychotherapy for PTSD.

The college describes the international legal status of psychedelic and related substances as “a rapidly changing area” and “it is possible these substances could soon be legalised for clinical use in various jurisdictions”.

Prof Howes said RCPsych supports the use of licensed drugs in a clinical setting, but stressed the college does not recommend people “self-medicate” in “back-street clinics”.

He added: “It’s very clear that you need to do this in a controlled clinical setting.”

Professor Owen Bowden-Jones, RCPsych registrar, said: “Our guidance will help academics assess the effectiveness and safety of psychedelics and ensure patients receive the maximum possible benefit from their use.”

Celia Morgan, professor of psychopharmacology at the University of Exeter, said RCPsych’s position statement is a “very encouraging development for the onward progress of psychedelic-assisted therapy within mental health treatment in the UK”.

“We welcome the guidance from the RCPsych as a professional body and hope that psychological professional bodies such as the British Psychological Society and BABCP (British Association for Behavioural and Cognitive Psychotherapies) follow suit.”

Dr Jo O’Reilly, chairwoman of RCPsych’s medical psychotherapy faculty, said properly trained staff are “key” in these treatments.

“Psychedelics can have a profound effect on the mind and may make some people more responsive to psychotherapy,” she said.

“Patients often find their psychological defences are lowered which allows traumatic and unpredictable material to emerge.

“The use of properly trained and supervised therapists is key to supporting patients in processing and finding meaning in their experiences. Patients can be in a particularly vulnerable state when under the influence of these substances and the therapeutic relationship is key to safe and effective practice, as with other psychological treatments.

“They should be supported through every step of their treatment, from initial preparation sessions to follow-up care.”