Ketamine and depression: miracle cure or too risky?
The believers claim that Ketamine has brought them back from the abyss, but how risky is it really?
“It is transformative and healing.”
“I feel unstuck.”
“I feel grounded.”
“For the first time I’m experiencing what it means to love my children.”
These are some of the comments from people who have used ketamine for treatmentresistant depression (TRD). Many have said it saved their lives.
One in five people will suffer from depression at least once during their lifetime. There are 23 known reports of suicide in South Africa daily. That’s according to the South African Depression and Anxiety group, (Sadag).
For every person who dies of suicide, 10 attempt to do so. The World Health Organisation says depression is the leading cause of disability in the world. Noone is immune.
James*, a 60-year-old professional from Johannesburg, knows all too well about suffering from depression. His bouts of depression started when he was about 15 years old. In his thirties they worsened. He says: “Even when I was surrounded by other people, I felt a profound sense of loneliness, of being unseen. It reached a point where I believed I was a burden on my wife and children and that they would be far better off without me.”
Despite years of regular counselling, he couldn’t shake off the feelings. Eventually, a psychiatrist prescribed antidepressants. Initially they helped, but they stripped him of emotions, good and bad. “They made me feel like a zombie. When I reached rock bottom, my doctor suggested I try ketamine infusions.”
What is ketamine:
Dr Duncan Rodseth, a psychiatrist at the Wits Donald Gordon Medical Centre, says Ketamine is a compound that was developed in the 1960s. It was approved by the US Food and Drug Administration (FDA) and registered as an anaesthetic in the 1970s. It comes with a long history. Initially it was used to treat injured soldiers in the Vietnam War. Coincidentally, they discovered that traumatised soldiers who attempted suicide were rescued from the edge after using the powerful drug.
It later became popular as a recreational psychedelic drug and was sometimes abused. In the 1970s the recreational use of ketamine and other psychedelics such as LSD and psilocybin was banned.
Rodseth says that in SA small dosages of ketamine, administered in a controlled environment, are increasingly being prescribed for off-label treatment. This could include posttraumatic stress disorders, anxiety, treatment resistant depression and obsessive-compulsive behaviour. It’s usually given to patients who have tried several other traditional antidepressants without much success.
Ketamine is mainly administered intravenously under the supervision of trained medical personnel. A form of ketamine has recently been developed as a nasal spray. It is also administered under medical supervision and has been registered for treating depression.
How is the treatment given?
James says the intravenous infusions last about 40 minutes.
They’re given in a quiet, semidark room with calming background music. A registered medical professional administers a small dosage of ketamine in a drip. One’s pulse and blood pressure are checked intermittently throughout the treatment.
“You’re always aware of what’s happening around you. I had the most incredible out-ofbody experience. Everyone and everything was connected. It was comparable to a profound spiritual experience. I felt completely at peace. Now I no longer fear death. It made me feel as if I were about to meet my maker,” says James.
The treatment took effect almost immediately and, soon after, he felt much lighter. Initially, James went twice a week. Now he goes about every five weeks. He says it has given him a life he never imagined possible.
Ketamine vs traditional antidepressants
Professor Ugasvaree Subramaney, head of the department of psychiatry at Wits, says ketamine works differently from traditional antidepressants.
On a simplistic level, antidepressants such as selective serotonin reuptake inhibitors (SSRIS) work by increasing the levels of serotonin in the brain. These chemicals help to improve mood and reduce symptoms of depression.
Ketamine, on the other hand, works by modulating glutamate, a neurotransmitter that plays an important role in controlling mood. Some people with chronic depression lose important connections in their brain which enable nerve cells to communicate. The regeneration of neural connections (called synapses) improves cell communication that regulates mood. This could explain why ketamine has a profound effect on depression.
Ketamine has many pros, but how safe is it?
Rodseth says one of the advantages of ketamine is that it works almost instantaneously, whereas traditional antidepressants can take weeks to become effective. That’s why it’s become so beneficial for patients who are suicidal. Ketamine doesn’t remain in the body for longer than a few hours though its effect can last for weeks. Unfortunately, since Ketamine infusions haven’t yet been FDA approved as an antidepressant, many medical aids don’t cover them. Ketamine nasal spray is registered but is considerably more expensive than standard medications.
Subramaney says antidepressants aren’t generally addictive. Rodseth adds that as far as we know, ketamine treatment is safe, provided that it’s administered in a controlled environment. Patients who receive small dosages have shown improvement in cognitive performance. The effect of long-term treatment is not yet known. However, there’s overwhelming evidence that it’s helped more than 80% of patients who suffer from treatment-resistance depression.
Professor Shabir Moosa, a family physician and executive director of AYZA Health, works in the public and private sector. He says the death of the wellknown Friends actor Matthew Perry has sparked new discussions on the dangers of using high dosages of ketamine. Perry drowned in a jacuzzi in his Los Angeles home in October.
If media reports are accurate, says Moosa, Perry ’ s postmortem described the cause of his death as mainly due to the acute effects of ketamine.
He ’ d struggled with alcohol and drug problems and had received daily ketamine infusion therapy for depression and anxiety — an unhealthy approach as it can morph into dependence. His last session was about a week-and-a-half before he died.
The medical examiner concluded that his death could not be linked directly to the last ketamine treatment he received because it doesn’t remain in the system for more than a few hours. It ’ s unclear how or when Perry received more ketamine.
The high levels found in his blood specimen levels were equivalent to the amount used during general anaesthesia and was very likely administered using tablets from the black market. Contributing factors included the effects of buprenorphine, a drug used to treat opioid drug disorder, coronary artery disease, respiratory depression and drowning.
Moosa says it’s extremely risky to self-medicate with ketamine or use it recreationally. Use of the drug has to be strictly controlled.
In SA, it ’ s been approved for anaesthetic use. Use for mental health is off label, meaning that appropriate health professionals can use it but are not allowed to advertise its use. The compounded tablet types of ketamine illegally pedalled online or distributed at parties are unsafe because you don’t know what you are getting.
In his experience, four out of five patients who receive ketamine infusions for depression and anxiety at the AYZA health care centre have seen remarkable results. The few who do not respond to the treatment don ’ t suffer any major negative side effects.
The long and the short of it is that there’s compelling evidence that ketamine administered in a controlled environment has given hope to thousands of patients who suffer from depression. It’s not available as a treatment for mental health issues at public hospitals. Moosa is hopeful that this will change.