Ketamine Off-Label

Talk about ketamine off-label and it’s hard not to get a raised eyebrow or two. The one-eyebrow raise is the curious, skeptical, quizzical, or disapproving look when someone hears about IV ketamine infusions for depression, just before she takes a deep breath and then dismisses it.  But the two-eyebrow raise is another matter entirely.

What Hope Feels Like

The two-eyebrow raise happens in men and women—or their spouses, parents, or adult children–when they see first-hand what hope feels like.  When the veil lifts, when the suicidal thoughts stop, when the anxiety falls away.  It is the sign of disbelief… but another kind of disbelief—not the one-eyebrow kind.  The kind of disbelief that shouts out amazement.  And hope.

There’s a face cream out there somewhere called Hope in a Jar.   IV Ketamine is like that—it’s in a vial, a sort of tiny, nondescript little glass jar.  And it offers hope for the relief of suffering to people with unrelenting depression…and anxiety…and suicidal thinking.  Symptoms that have lasted for months, or sometimes years on end.

Ketamine is nothing new.  It’s been around for more than 50 years as one of the safest and most widely used medicines in anesthesia. In the OR, in the ER, in pediatrics, on the battlefield, and around the world, even in the most primitive medical settings.  But for almost as long, it’s been stolen and used illegally at extremely high doses as a recreational drug for the “out of body” experience that people report.

“Special K”

Because of that, when researchers discovered several years ago that ketamine has surprising effectiveness against depression, it was hard to break through the credibility problem ketamine unfortunately acquired under its name, “Special K,” the street drug.

In fact, almost every headline in the press about ketamine tries to grab your attention with something sensational:  “Street Drug”  “Party Drug” “Special K”.

How about grabbing your attention with this:  Hope.  Relief.  Resilience.

To someone with depression, anxiety, or PTSD that won’t stop, hope is new.  And even though ketamine isn’t new, the way we’re using it is completely new, and fresh, and offers a way out of despair for people who have just given up on feeling better.

Research studies using ketamine have exploded, and demonstrate that low doses of intravenous (IV) ketamine provide remarkable anti-depressive benefits.

In fact, it goes way beyond “benefits.” In a mountain of cases, IV ketamine off-label provides remission from depression and anxiety in people who can’t remember a time when they weren’t depressed… as well as suicidal.  

And get this: in most cases, those who’ve been suicidal feel relief within an hour or two. This is remarkable and unheard of before in an anti-depressant, since before now anti-depressants have required weeks or months to provide full benefits.

But there’s a problem.

A problem…?

How can there be a problem with a medication that brings relief and even remission from depression and anxiety for a huge percentage of people who’ve not received relief from other antidepressants?

It sounds more like a miracle than a problem…!

The answer is simple.

Off-Label Ketamine Use

While the FDA has approved ketamine for use in anesthesia, it hasn’t been approved by the FDA for use as an antidepressant.

Is ketamine the only drug that’s used for off-label purposes?

Absolutely not.

Other Medications Used Off-Label

When the FDA approves a drug for a given purpose, the drug is approved for use. Physicians begin to prescribe it for that indication but are free to use their expertise and best judgment to prescribe it in other circumstances, too. And it’s not unusual for “side effects” to emerge that are so beneficial that the drug is prescribed for the side effect more often than it’s prescribed for its original use. In fact, 20% of the prescriptions written these days are for off-label uses.

Surprising, isn’t it?

One example of drugs commonly used off-label is beta blockers. These medications are approved by the FDA to control blood pressure, but cardiologists know they’re also very effective and widely accepted as standard medications in the treatment of heart failure, too.

Psychiatrists prescribe them for performance anxiety, stage fright, to treat tremor and restlessness, and sometimes to reduce aggression. 

Even though they haven’t been approved by the FDA for those uses, they’re widely accepted and prescribed as the optimum treatment for entirely different problems than the ones they’re approved for.

Another example is the drug trazodone, which is approved for use as an antidepressant, but is usually prescribed off-label for sleep. Also, amitriptyline, approved as an antidepressant but prescribed off-label to prevent migraines, to treat nerve pain, and to improve motility.

Or metformin, a diabetes drug which is prescribed off-label to reduce food scavenging and promote weight loss.

So, many drugs are prescribed for off-label uses at some point. Some are so widely used for the off-label use their original purpose is all but abandoned.

Risks With Off-Label Use

That’s not to say there are no risks in prescribing medication off-label.

There are.

Plenty of risks exist for both the patient and the physician. Risks always accompany our looking outside the box. And occasionally a drug is used off-label and, because there hasn’t been enough testing, tragic outcomes result in the drug being removed from the market.

But that’s a very, very low risk for ketamine. Anesthesiologists have been using ketamine for decades in much, much higher doses than the the doses studied to treat depression and anxiety.  This is not an untested drug.  It’s safe, with minimal side effects that dissipate in minutes.

IV Ketamine infusions used off-label for depression require fractional dosages of ketamine compared to other uses, with minimal side effects that wear off in minutes. And the results are extraordinary.

Safe, FAST, and So Effective

People who’ve suffered throughout their lives with depression so severe they’re  looking for an exit, are experiencing restored lives from the lifting of depression. They feel relief and renewed creativity that improves almost daily throughout their initial IV infusion course.

These most critically depressed patients often experience relief from suicidal thoughts within the first hour or two after their first IV ketamine infusion.

You’ve heard that traditional antidepressants–SSRIs, or selective serotonin reuptake inhibitors and others–work through the monoaminergic system on specific neurotransmitters. 

But we’ve moved way beyond talking about monoamine neurotransmitters in psychiatry. 

We talk about inflammatory cascades across the blood-brain barrier. New signalling systems. Dendritic branching and synaptic density. Neural networks.  

New lingo.  New news.  New hope.

Ketamine works to bring balance to the body’s glutamate signaling system, a different system that hasn’t been addressed before in depression treatment.  Ketamine works in a startling and effective way:  it stimulates mRNA through the mTOR pathway to remodel neurons. 

Wait.  Say that again.

Ketamine turns on DNA to actually stimulate the growth and branching of neurons and to create more dense connections between them.  It can literally stimulate the remodeling of neuronal trees and improve neuronal rearborization.

English, please.

Ok, here we go:  IV ketamine infusions flip the DNA switch to “ON” to help neurons regrow the branches and connections that have been pruned away by stress. 

This is extraordinary. 

It’s so exciting that we should be throwing ourselves into studying it further, waking up early, reading voraciously, giving TED talks.

And low-dose ketamine infusions do several other nifty things  that we’ll talk about in future posts. Things like bringing into balance the body’s glutamate signaling system–a different system that hasn’t been addressed before in depression treatment.

So addressing that imbalance ignites a whole new hope for depressed patients.

A New Approach

This alternative approach to treating depression and anxiety has so many benefits. It works fast, often within an hour. And continues to relieve depression through the weeks of treatment. Those treatments can provide depression and anxiety relief that lasts for weeks or months, or perhaps much longer.

As far as safety, there hasn’t been extensive testing for the long term effects of ketamine off-label use in depression. But there’s still the data from decades of ketamine use for anesthesia. As an anesthesia medication, the doses are much much higher, and it’s a safe drug with minimal, time-limited side effects.

Some people achieve remission after one treatment.  But most need a short series of IV ketamine infusions over about 2 weeks to achieve remission—and still others need a bit longer. There are those who need maintenance doses to keep their depression at bay . Still, for those who are helped, this off-label treatment is a life-saver.

It’s hope. Pure and simple. And exhilarating.

Ketamine: Life Saving Innovation

So, it’s true this use of ketamine off-label hasn’t been through the scrutiny of the FDA’s approval gauntlet.  Even so, the literature has shown striking benefit to severely depressed patients who have not received effective treatment in the past.

If your results from your depression and anxiety medication have been unsatisfactory, consider exploring a breakthrough option.  Please do call for an appointment. 

We’ll learn so much about you and the factors that can help predict your response to IV ketamine infusions through a thorough evaluation. 

I look forward to meeting you.

To restoring you to your best self,

Lori Calabrese, MD