- I've had depression since I was like 12.

- I was on at least 10 different psychiatric medications.

- So I was really interested in ketamine as an alternative to being on medications for the rest of my life.

- You feel very warm and fuzzy.

You feel very euphoric.

- It just feels sort of like swirly or something.

Like your hands don't totally work exactly how you're telling them to work.

- I honestly felt results in like a couple of days.

It honestly like saved my life.

- Getting outta bed was a little bit easier.

It's really just like the little things I guess that add up that really make you feel better.

- Your social media timeline might be full of personal stories and ads about ketamine therapy and you're not alone.

What was once an infamous party drug is now also a mainstream treatment for depression.

Typical antidepressants take four, maybe six weeks before patients start to see some positive effects.

But with ketamine folks who have treatment resistant depression who've tried all kinds of depression treatments with no luck, sometimes feel relief much faster.

We're talking a matter of hours, not weeks.

All of this interest jumped off in 2019 when the FDA approved Spravato or esketamine a nasal spray drug derived from ketamine and used with oral antidepressants to treat depression.

But ketamine, which the FDA originally approved as an anesthetic in 1970, was already being used for mental health treatment off-label.

That is to say legally, but in ways that go beyond the drug's FDA-approved uses.

We're talking ketamine IV infusions and oral lozenges prescribed in specialty clinics and even at home via telemedicine for anxiety, OCD, PTSD and more.

This surging use has some clinicians and experts concerned that patient safety is being sacrificed.

So what's the real deal with Special K?

(inquisitive music) Now typical antidepressants are based on the serotonin theory.

The idea that depression comes from an imbalance in brain chemicals, neurotransmitters like serotonin.

Hate to break it to you, but recent research has shown that it's actually not so simple.

The complex multifactorial pathways that lead to depression are still pretty unknown.

- Ketamine appears to work by a mechanism that's quite different than most of our standard oral antidepressants.

Ketamine primarily targets another neurotransmitter called glutamate.

Glutamate is the most ubiquitous, abundant neurotransmitter in the brain.

So ketamine works at one specific receptor called the NMDA receptor for glutamate.

That then excites a cascade of events downstream that actually generates the antidepressant effect.

- Now, if you've had it with your SSRIs which are ineffective, for many patients, this new approach might sound exciting but nothing is a cure all and that goes for ketamine too.

The most robust research supporting ketamine therapy is for treatment resistant depression and suicidality.

And that's also what researchers studied with esketamine or Spravato.

In the trial, more than half of patients' depression symptoms went into remission after four weeks.

Worth noting again they also took oral antidepressants during the trial.

But what makes esketamine so different from off-label Ketamine therapy?

- Their safety profiles are similar.

The efficacy is very similar as well.

The Esketamine nasal spray is patented thus has more benefit to a pharmaceutical company.

Generic ketamine is made up of molecules that are basically mirror images of each other and they basically isolated out one of the mirror image molecules and then they studied that and they have it under patent.

There is less incentive to study the off-label use of the generic ketamine, mostly for financial reasons.

You can't patent the generic ketamine anymore.

It's just been around for too long.

- Most of the large studies that have been done and the and the reason these studies are incredibly expensive to do have been done through the pharmaceutical industry using esketamine.

But it doesn't mean that alternative treatment approaches are not effective or are not safe.

It just means we can be less confident in what we say about those treatments for those patients.

- For the generic ketamine formulation we do have high quality evidence that ketamine IV infusions can successfully treat depression and suicidality and are safe and well tolerated with the usual protocol.

A handful of doses over a few weeks with occasional booster doses in the weeks and months afterwards.

These infusions are common in clinics that administer ketamine and may be more suitable for higher risk patients.

But here's where it gets tricky.

- There's always this tension about providing the safest highest quality treatment you can provide but not making it so inaccessible that nobody can actually get the treatment.

- Though Spravato or esketamine can be covered by insurance which is a good thing because the first two months of treatment can run several thousand dollars, most insurances will not cover intravenous ketamine.

Those off label infusions can cost several hundred dollars each.

But ketamine, the drug itself is cheap and policy changes during covid loosened laws around telemedicine making all kinds of medical care more accessible.

Enter ketamine telemedicine: online services that quickly and affordably connect you with a provider and a month's prescription of ketamine in tablet or lozenge form.

The price tag and accessibility are great for a lot of people, but researchers and clinicians have some concerns that in some cases patients are taking ketamine more frequently and for longer periods of time than what is generally considered to be safe.

- This is not something you just want to treat with a medicine and then not have close follow up.

It has significant effects on some of your physiologic features such as heart rate, blood pressure.

And then there's also the psychological part, where ketamine can have pretty profound effects on cognition and perception and and that can lead to some pretty concerning situations.

- We know from just talking to people that they often don't take medications as prescribed.

If you start taking higher doses every day that's when you can start to see bladder issues.

- There hasn't been great evidence of people becoming physically addicted to ketamine.

It's not like, you know, an opiate drug but we know ketamine is a drug that is misused.

We don't know exactly where that point tips and where it goes from safe use or relatively safe use or a much higher risk of use.

- There's also evidence that ketamine therapy may be able to help with other psychiatric conditions as well like anxiety, PTSD, OCD and substance abuse.

And these are benefits that telehealth providers are advertising.

But does ketamine actually help with these conditions?

- The largest body of high quality evidence has been collected for esketamine in treating patients with unipolar depression accompanied with suicidal ideation or suicidal thoughts.

We don't really have the high quality data to say with confidence that it is or it isn't so effective in these other treatments.

- In our clinic, I'll just say I will treat someone with depression, suicidal ideation, anxiety, OCD.

It actually turns out it's it seems to be quite effective for OCD.

So if I can prove that like this many other patients have benefited I'm able to do that.

- I felt an effect after the first six sessions and then it started to go away, went back had a little bit, you know of improvement and then went back to feeling depressed.

- Ketamine's antidepressant effects are generally considered to be transient meaning depression symptoms could return once you stop treatment in the weeks or months that follow.

So with that being said, is ketamine really the silver bullet we should rely on long-term?

- I don't think there's a magic bullet for anything.

I think you have to look at each person individually and really look at what's causing any particular mental health issue.

If we're using ketamine as an antidepressant it essentially is just suppressing symptoms.

- This is why some clinicians say ketamine like other depression treatments, work best alongside talk therapy and other support a different version of ketamine treatment itself: getting therapy while under the influence of the drug.

That's what Dr. Hannah Mclane does.

- So ketamine is interesting 'cause it actually in in many ways dissociates a person to allow them to gain perspective.

As a psychoanalyst, we think of trauma as unprocessed memories.

We don't really like thinking about them but then we somehow we end up functioning with them almost like they were driving all of our behavior.

But what we're actually doing in psychedelic therapy is we're trying to go into the issue like, why are you anxious?

Why are you depressed?

And oftentimes that is very deep and it's very like core of your being.

The data on this is really early.

There's not that much work that's been done comparing psychotherapy with and without psychedelics, but it's coming.

- And now for some parting advice.

First, vet your ketamine therapy provider.

Find out who's on staff.

Are there enough mental health practitioners to support your individual needs?

Is there a plan in place to ensure your safety or lower your risk of dependency and addiction?

And like I always say, consult your doctor first.

If you experience mania, psychosis or substance use disorder or if you're at risk for heart disease ketamine therapy might not be right for you.

And finally, some of the depression and anxiety we all feel is situational and rooted in systemic issues that sometimes feel like they're completely out of our control.

If this sounds like you you might wanna check out our last episode where