If you could talk to someone who is considering ketamine for depression – or, who has never heard of ketamine but is looking to manage their depression – what would you want them to know?
Their suffering, which is a consequence of this common – and in many cases, lifelong and severe – condition that we call depression does not need to happen. People need to know that there is hope and that we have treatments that are highly effective, rapidly effective, and effective when other conventional approaches to depression just have not been successful.
People with depression often are hopeless and discouraged or suffering, and they try conventional approaches – things like Prozac-type (SSRI) drugs and so on – and things just don’t improve sufficiently for them. And – no surprise! – it just adds to the hopelessness and helplessness.
Ketamine represents hope. Ketamine represents a safe, highly efficacious innovation to treat depression, to treat depression rapidly within one to two days, and to treat depression when other treatments have failed. That’s a really, really important message for people who are hearing about, thinking about, and talking about ketamine for depression.
What makes ketamine so different from other treatment options?
The mechanism of action of ketamine remains unknown. As it is for all medicines in psychiatry, we don’t have this fully unraveled. But, we do have very, very strong data indicating that its mechanisms of action are completely different from any of the drugs we’ve had.
The first antidepressants we had in psychiatry began to appear in the mid to late 1950s in Europe. For the most part, since that time, the mechanism of action of these drugs – at least as we understand it – have been largely similar. There’s that phrase: if you want a different outcome but keep doing the same thing, that’s the definition of insanity. You obviously need to have a different mechanism.
Ketamine works through glutamate, which is a very different mechanism. The FDA believes it works through glutamate, which is a different mechanism than the Prozac-like drugs that are largely targeting serotonin.
So, this is the first glutamate drug. The relevance of that is not only that it’s a different molecule; it’s also related to the fact that glutamate is implicated in the brain disease of depression directly, and ketamine targeting glutamate directly results in an immediate improvement of symptoms and an immediate reversal of some of the underlying brain abnormalities seen in depression.
So, I always use the metaphor of going to the airport through the usual line. It takes quite a bit of time to get through security. And then, there’s the fast-track line. You end up in the same place, but one lane is faster. Ketamine gets you through security faster, so to speak, than the regular line. The regular line is the Prozac-type drugs.
If you went to a care provider with pain, and the care provider said, “take this pill for your pain, it takes six weeks to work,” you’d be scratching your head and thinking, “that doesn’t make any sense to me.” That’s what we do with depression. We have treatments that can alleviate pain, alleviate suffering, and disability, and it works in an entirely different mechanism called glutamate.
Why hasn’t ketamine been widely used to treat depression, if it’s so effective?
There are a couple of reasons for that. First, ketamine is relatively new. We’ve had the old guard treatments for six to seven decades.
The second reason is that because it’s new, there’s less familiarity with its profile, safety profile, efficacy profile, and frankly, just the literature around it.
Thirdly, healthcare systems are set up in such a way that the primary care clinician is the one who typically sees people with depression across America and around the world, and they’re the ones who prescribe most antidepressants. Ketamine treatment has not been a treatment in the healthcare world, which is a healthcare system issue.
I think that when you look at how antidepressants are prescribed across America, the prescriptions are, to some extent, influenced by the science and the clinicians’ discussion with the patient. But they’re often largely influenced by the reimbursement environment and formularies. Ketamine is not necessarily found in many formularies, and that’s another very important aspect.
When it comes to ketamine, we just don’t have sufficient access to the treatment. It’s not as though you can walk into a primary care office, which is ubiquitous across the country for it. We don’t have that level of availability for it yet. Especially if you live in an urban place, as compared to a rural place.
One final factor: there has been some concern about ketamine. It has a history. It’s been used in other areas of medicine; it has a history of abuse and misuse that’s been described. It’s been used as a party drug. It doesn’t come with a clean slate; it comes with a history.
Some people – very appropriately – have concerns. Is this an appropriate treatment? Am I going to usher in some drug abuse problem if I’m a patient? People are, unfortunately, very familiar with the opioid epidemic that is going on, and no one wants to repeat that ever again.
When is someone ready for a ketamine treatment?
I think people who are experiencing symptoms of depression, especially ones that have tried more conventional approaches that have not been successful– need to see a care provider, and a care provider should be asked if ketamine is something they would consider, or if they can refer them to someone who can have a consultation around ketamine.
I do think that there needs to be some type of consultation or triage, and once that takes place with someone who has familiarity with ketamine and depression and its implementation, then the patient would be ready. It’s a fairly straightforward process to determine someone’s eligibility.
Ketamine is widely used by anesthesia providers. That’s one of its origins, anesthesia. It’s very popular in anesthesia, in large part because it’s so well tolerated. In fact, it’s on the World Health Organization’s List of Essential Medicines. It’s really been around for fifty-odd years. Approved in 1970, generic, and used for a long time. A person is ready once they’ve had a visit with a care provider who has competencies and knowledge in the implementation of this treatment.
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