Ketamine can be life-saving or lethal psychiatrists warn
The anaesthetic drug ketamine can bring life-saving hope for people suffering treatment-resistant major depression or at severe risk of suicide, but unsupervised use or excessive dosages hold addictive and even lethal risks.
This is the warning sounded by the South African Society of Psychiatrists (SASOP) against the “recreational” or unsupervised use of a drug for which scientific evidence is mounting worldwide as a new treatment for adults with severe depression that has not improved with conventional anti-depressant treatments.
“There is good evidence that ketamine in low doses, administered under controlled conditions with the necessary medical supervision, is an effective treatment for treatment-resistant major depression. It is also effective in acute cases of suicidal ideation, rapidly reducing the risk of life-threatening thoughts and acts.
“However, ketamine is a powerful anaesthetic agent, and a too-high dose can cause sedation and loss of consciousness, and in very high doses may cause dangerously slow breathing and the risk of death.
“Even at lower doses, if administration of ketamine is not adequately supervised and the person is not in a safe, controlled setting they may become confused and inadvertently harm themselves. Ketamine is also potentially addictive and open to abuse,” said SASOP spokesperson, psychiatrist Dr Bavi Vythilingum.
Ketamine is an anaesthetic originally used in animals since the 1960s, in humans since the 1970s, and is listed in the World Health Organization’s List of Essential Medicines as an anaesthetic. It is registered in South Africa for induction and maintenance of anaesthesia.
The drug’s efficacy in sub-anaesthetic doses as a novel treatment for treatment-resistant depression in adults has gained evidence over the past two decades.([i])
However, Dr Vythilingum said the rising number of “independent” clinics offering ketamine treatment for depression and other mental health conditions is cause for concern, regarding correct diagnosis and whether ketamine is the appropriate treatment, as well as monitoring and management of possible side-effects.
She also emphasised that ketamine is indicated only for treatment of adults with treatment-resistant depression; evidence does not support its use in treatment for children.
Although some claim that ketamine is effective in treating other mental health conditions such as post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), SASOP cautions that there is limited scientific evidence for this.
Dr Vythilingum said research had shown several positive effects of ketamine on the brain which contribute to its efficacy in treating treatment-resistant major depression, including that it improves the production and functioning of the neurotransmitter glutamate, which plays a role in mood, thought patterns and cognition.([ii])
Ketamine has a different mechanism to traditional anti-depressant medications, which is believed by medical researchers to be at least part of the reason for its effectiveness where other treatments have failed.([iii])
Ketamine is administered by intravenous infusion (a drip) over 40 to 50 minutes, and the patient given enough time to recover afterwards. The patient should be fetched after the treatment and should not drive until after they have had a full night’s sleep.
Initial treatment takes place in six sessions over two to three weeks, and the treating psychiatrist may prescribe maintenance treatment on a case-by-case basis.
The dissociative state (“trip” in common language) caused by ketamine can produce feelings of a trance-like state or hallucinogenic experience, feelings of an “out-of-body experience”, feelings of unreality, visual and sensory distortions, and euphoria or “a buzz”.
“For this reason, it is important that the setting is safe, meaning that it is quiet and private, that treatment is medically supervised, that the patient is not left alone during treatment and recovery, and that the facility is equipped to manage any adverse side effects,” Dr Vythilingum said.
While the dissociative side-effects can also be a positive in improving depressive symptoms, she said other negative side-effects could include nausea and vomiting, raised blood pressure, respiratory depression (slowed breathing), sedation and unconsciousness.
Long-term use of ketamine at high doses can cause bladder, kidney, liver and stomach pain or toxicity, as well as addiction demanding increasingly higher, life-threatening, doses.
“Ketamine for psychiatric treatment must be prescribed by a psychiatrist, as only a psychiatrist can diagnose that depression is treatment resistant. That diagnosis is made following at least two courses of conventional anti-depressant medication with no improvement in symptoms.
“The drug must be administered by a medical doctor, and both physical and psychological safety are paramount during administration of ketamine,” Dr Vythilingum said.
SASOP advises that the guidelines issued by the South African Society of Anaesthesiologists (SASP) should be adhered to. These guidelines state that the medical doctor administering ketamine must be an anaesthesiologist or registered sedation practitioner who is qualified in advanced cardiac life support and resuscitation.
“Ketamine must be administered in a facility equipped for physiological monitoring (blood pressure, pulse rate, oxygen saturation), with medication, equipment and qualified personnel to manage adverse physical or neurological events, including hypertension, cardio-respiratory events, airway management and resuscitation.
“The administering clinician or member of the team should also have expertise in mental health and managing patients who may become agitated, anxious or otherwise distressed. A psychiatrist should be available in case of a psychiatric emergency,” Dr Vythilingum said.
Ketamine is not considered safe for patients diagnosed with schizophrenia, nor for those with a history of substance abuse.
Dr Vythilingum also cautioned that while there was clear evidence for the off-label use of ketamine in treatment-resistant major depression, more research was needed on the drug’s long-term effects, side-effects and safety as a psychiatric treatment.
REFERENCES
[i] McElvery, R. 2022. The Past, Present and Future of Using Ketamine to Treat Depression. Smithsonian Magazine. https://www.smithsonianmag.com/science-nature/a-brief-history-of-ketamines-use-to-treat-depression-180980106/
[ii] See: Meisner, Robert C. 2019. Ketamine for Major Depression: New tool, new questions. Harvard Health. https://www.health.harvard.edu/blog/ketamine-for-major-depression-new-tool-new-questions-2019052216673
[iii] See: Meisner, Robert C. 2019. Ketamine for Major Depression: New tool, new questions. Harvard Health. https://www.health.harvard.edu/blog/ketamine-for-major-depression-new-tool-new-questions-2019052216673