Ketamine
Ketamine has been used safely and effectively for many different conditions since it was discovered in the 1960s. Primarily, it was found to be a useful medication to sedate patients during procedures because even at high doses it doesn’t reduce blood pressure or breathing rates unlike opiates and other fast acting sedative medications available at the time. What many don’t know is that from the very beginning it was being investigated for its potentially beneficial psychiatric effects.
Ketmine was found to have many different psychedelic effects, and was classified as a “dissociative anesthetic” from the beginning. While other drugs used for sedation reduce overall brain activity, ketamine was found to increase brain activity in some complex ways. New research shows that low and medium dose ketamine actually increases connectivity between brain regions and can change the way that the brain is able to rewire itself, a process called plasticity. While this effect doesn’t last forever, the window of increased connectivity can last for days after an infusion and is being investigated as a tool to improve learning, creativity, and psychotherapeutic techniques designed to break unhelpful cycles of negative thinking and hopelessness.
This is possibly why it has been found to have a rapid effect on even very severe depression. While standard antidepressants don’t become fully effective for weeks or months, patients describe nearly immediate benefits with ketamine. Moreover, while very few medical treatments have a measurable effect on suicidal thoughts, the majority of people treated with ketamine have a significant reduction in a desire to die within hours. Seems like a miracle, right?
It is important to know that disrupting bad brain networks and allowing new connections to form isn’t enough for long term success. It takes work to rewire those networks and this often involves psychotherapy. This has led to investigations looking at psychotherapy before, during, and after ketamine. These studies are hard to analyze, but very low dose ketamine during psychotherapy does seem to have some benefits at enhancing the therapy in a few ways. However, other studies show that higher doses (still much lower than used in sedation) infused over longer periods of time are required to genuinely disrupt those misbehaving brain networks. Whether there is a proper ketamine dose for use during psychotherapy is unclear, but it is very clear that therapy prior to and after ketamine use is very helpful if not vital for long term improvements.
How is ketamine given? Many virtual clinics are popping up with relatively inexpensive ketamine by mouth. While this would be great if effective, the data hasn’t shown any robust or lasting benefit when ketamine is given as a tablet or a sublingual pouch. A nasal spray (designed so that a drug company could patent a very old medicine) was thoroughly studied but with very minimal benefits. The best data comes from IV infusions where someone is given a slow drip of ketamine in a fluid bag over a period of time. The biggest studies have shown that when patients receive 6 infusions over the course of two weeks, each infusion lasting an hour, the benefits are remarkable and can last for months. Much smaller studies have investigated ketamine injected into the muscle or under the skin with some promising results, but likely not as promising as IV treatments for many reasons.
Why isn’t everyone giving ketamine to these patients then? It is complicated. Psychiatrists are the best people to monitor the benefits, but most psychiatrists are very uncomfortable with anesthesia drugs and IV infusions. Because ketamine isn’t patented, no one will ever pay for the process of FDA approval, and so insurance companies may never reimburse for it. One might imagine that IV ketamine could be given in an Urgent Care, ER, or a psychiatric unit, but there are political and business reasons that this is very difficult.
The reality is that IV ketamine treatments for depression are one of the most novel, effective, and inaccessible treatments in modern medicine. Many clinics have popped up, run by psychiatrists uncomfortable with complex medical monitoring or pain doctors who aren’t trained to monitor the psychological effects. They are all self-pay because insurance will not reimburse the treatment, and the typical cost is between $400-$800 per infusion (between $2400-$5000 per series of 6 infusions). By contrast, getting an oral lozenge online from a ketamine provider for $60 may feel like a bargain, but if oral and sublingual ketamine isn’t nearly as effective as IV treatments as the research indicates, it can be a bigger waste of time and money.
What else can Ketamine help with? Studies show it may help a variety of obsessive disorders including OCD, ruminative anxiety, and recurrent negative self talk. It has been shown to help reduce cravings in addiction as well. While the data is less clear on some other conditions, and no other conditions have been studied as much as Treatment Refractory Depression, more research is ongoing and all of the initial results are encouraging. A little different from the depression data, and a major avenue of potential interest is chronic pain. Obviously there is an enormous amount of data on ketamine for use during procedures, but typically those doses are much higher doses that cause anesthesia.
Some recent analyses have shown that use of ketamine during and reduced dosing after procedures can reduce more severe pain and delirium after the ketamine is stopped. Lower doses of ketamine given by mouth or with nasal sprays was a very hopeful avenue for patients with chronic pain, but the studies show the effects are minimal and inconsistent. The depression protocol for IV ketamine shows some improvement, but it doesn’t have the same lasting effect that it does for melancholia and depression. When chronic pain and depression are both present, the depression protocol is much more effective for the chronic pain, but it is unclear if that is just due to the effects depression has on chronic pain. But when someone is about to spend $3,000-$5,000 on a procedure, they want an expectation that it will help a lot and for a long time. Unfortunately, these standard 6 sessions, each about an hour long, doesn’t have the same robust effects for everyone.
That isn’t the end of it though. When studies have been done on longer infusions, there is a much more robust effect on certain types of chronic pain. If infusions last 4 hours, given in about 3-5 sessions, the data shows that the benefits are much greater and last a much longer period of time. Even more robust is when very long infusions are done, typically around the clock for about 4 days, where a majority of patients had significant reduction in various types of pain lasting for months. If you look particularly at patients who have changes suggestive of Complex Regional Pain Syndrome (pain out of proportion to injury, atypical coloring, sweating, and temperature, and neuropathic features) then the data is even better. If you test these patients by doing an easy but invasive procedure with a numbing agent injected near the spine called a “sympathetic block” and see that pain improves briefly, then the results of a ketamine infusion are more consistent. Clearly, the data is still evolving, but a tiered model of treatment makes the most sense. If a patient wants to try the daily or weekly oral options first, that may help some. The depression regiment of 6 infusions an hour long may significantly help the affective dimension of pain, often a major portion of the total pain, as well as a moderate benefit for some types of peripheral pain. If those infusions aren’t effective or the pain is part of the complex regional pain syndrome, then starting with or quickly escalating to 4 hour long infusion sessions is reasonable. I generally recommend that if there is not significant benefit after the third session, consideration should be made for very long infusion times.
The problem? No one provides very long infusions (>24 hour) and finding someone who will provide a 4 hour infusion is nearly impossible. There are many reasons for this, but the main ones involve financial decision making on the part of providers. Keeping a room available with staffing for over 4 hours is very costly, even if the time spent by the provider is minimal. Insurance companies, as discussed, also provide no real compensation for the procedure. While people are paying very large amounts of money for other treatments, the lack of availability, profitability, and publicity about ketamine treatments.
To learn more about the availability of ketamine, the potential risks and benefits of the procedure, and how you can determine a ketamine solution for you, request a consult today.
