Millions of people suffer with Treatment Resistant Depression (TRD) and other challenging mental health problems, such as Post-traumatic Stress Disorder (PTSD), Bipolar Disorder (BPD), Obsessive Compulsive Disorder (OCD), and excessive anxiety. More than 300 million people worldwide are suffering from depression, and often none of the marketed antidepressants can help with their condition. Depression, according to the World Health Organization, is the leading cause of disability and, in extreme cases, leads to suicide. Every year, 800,000 people commit suicide worldwide, most of them suffering from severe depression.
Many drugs are prescribed for depression. The problem is that they work on only half of the patients. Therefore, it is not surprising that typical antidepressants do not help many people at all. STAR * D, one of the most cited and most comprehensive studies on the most commonly used antidepressants, shows that more than half of people remain symptomatic after trying several different drugs (1). “And many of them were relapses; suggesting that antidepressants don’t work the way we originally thought,” says Robert McClure, MD, an associate professor in the Department of Psychiatry at the University of North Carolina.
Ketamine changes a lot
Ketamine is not a new drug. It was developed in the 1960s and used as a painkiller during the Vietnam War. “Ketamine has proven to be a very suitable drug for surgery because the patient didn’t know what was going on with it, as ketamine turns off the functioning of the cerebral cortex,” McClure explains.
But scientists only began to investigate decades later whether ketamine treatment could be used as an antidepressant. Unlike drugs that target monoamines, ketamines act on another neurotransmitter, glutamate. Drugs that suppress NMDA receptor activity, such as ketamine, improve stress response in rodents (2). Researchers at Yale University have found that ketamine also improves the symptoms of major depression in humans (3). In 2006, ketamine was found to be effective in those who had not responded to other treatments (4), although they had tried more than six different antidepressants. Ketamine has also been shown to be effective in suppressing suicidal thoughts (5).
That was an important change, “says McClure.” Because no new drug for depression has been discovered for many years. ”
In addition, ketamine can be used much faster. “Anyone who has ever taken antidepressant pills knows that their effects don’t show up until weeks later,” McClure says. “Ketamine, on the other hand, works within 24-48 hours.”
But because ketamine isn’t new and therefore unpatentable, meaning you can’t make a lot of money from it, pharmaceutical companies have tended to compete over which one will first develop an agent that mimics the way ketamine blocks NDMA receptors. Then, in 2019, the U.S. Drug Administration licensed esketamine or Spravato nasal spray (6).
“Ketamine can switch the brain from a major depressive state to a much better mood in as little as an hour.”
However, McClure also stresses that comparative studies of a large sample have not yet been conducted, so it is difficult to say which works better. It is easier to administer the drug intravenously to a patient, but nasal spray is more likely to be funded by insurers because intravenous ketamine is still considered an “experimental” phase of treatment.
It is a prescribed medication and a tool
Some professionals see ketamine as a tool to understand the biological causes of depression, and thus one day it may be possible to cure the disease. “Ketamine provides an unprecedented opportunity to study how the brain transitions from depression to good mood in a matter of hours,” says Chadi Abdallah, MD, a psychiatrist at the Baylor College of Medicine’s Institute for Psychiatric and Behavioral Stress Syndrome. Associate Professor of Neuro-Psychiatry.
MacMillen also likes to view ketamine as a fertilizer that makes the soil in our garden more fertile. “Ketamine very rapidly increases the activity of the neurotransmitter glutamate in the frontal lobe of the brain, which shows reduced activity in depressed people. This creates new connections between nerve cells in that area and allows the old ones to regenerate.”The synaptic loss caused by depression can disrupt certain networks in the brain that are restored by ketamine, at least temporarily.
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Scientific literature:
1. https://www.nimh.nih.gov/funding/clinical-research/practical/stard/allmedicationlevels.shtml
2. https://pubmed.ncbi.nlm.nih.gov/2171955/
3. https://www.sciencedirect.com/science/article/abs/pii/S0006322399002309
4. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/668195
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671489/
6. https://www.spravatohcp.com/trd/what-is-spravato#what-is-spravato