Why do we always talk about IV ketamine for treatment-resistant depression, rather than just ketamine? Can’t we give it any old way…ketamine IV, IM, or IN for depression?

Why is it so important that it be given as an intravenous infusion, rather than as an intramuscular injection or an intranasal spray?

Ketamine IV, IM, or IN for Depression

Like lots of medications, ketamine can be given in a variety of ways.  But are they all advantageous to you? 

We don’t think so.

Not all physicians insist upon IV administration of ketamine, if they offer ketamine as a treatment for psychiatric disorders at all. But at Innovative Psychiatry, this is the only way we provide this medication.

We’re finicky.  We’re perfectionists.  We want to make sure we know the exact dose your brain receives so that we make sure you get the absolute best possible results from your treatment.

Did I say that right?  Exact.  Absolute.  Best.  That’s what intravenous ketamine offers as an advantage over any other method.  It makes your best – or getting back to your best self – possible.

This is where we start swimming with sharks.  And this is where the research and the experience and the opinions about what to do and how to do it get interesting.

Bioavailability

What’s bioavailability anyway??

It’s the amount of medication that your body is actually able to use.  Not how much you’re given, but how much your body sees and can use.

So … it means the active portion that reaches your blood stream and that can actually be useful to you.  The portion that treats what’s bothering you.  The rest is altered, digested, excreted, or otherwise discarded by your body.

Make sense?

Why IV Ketamine?

OK.  Basically, we want to be sure we know the exact dosage you receive, so we can know you’ll get the very best results.  And intravenous infusion is the ONLY route where 100% of the ketamine you are given is 100% available to your body and 100% able to get to your brain.  Which is exactly where it needs to be. 

So how can we predict the exact dosage your brain will see?

Well, with an IV infusion, your ketamine dose is determined by your body weight that day and calculated down to a tenth of a milligram.  Then it’s mixed with saline and slowly “infused”  directly into your blood stream the same way that fluid is given to someone who’s dehydrated.  (We love the word infusion — as in “infused with hope.”)

With an IV infusion, there are no obstacles preventing that perfect entry into your bloodstream and on to your brain. Anesthesiologists have known this for decades.  Ketamine was designed to be given IV.

Why Intranasal Ketamine Is Unpredictable

But that’s not the case for other routes, which do present obstacles to the drug before it reaches the blood stream. I’ll show you what I mean.

When ketamine is given as an intranasal spray, it has to pass through your mucous membranes to reach your bloodstream.  So first, it has to be suspended perfectly and evenly in a mist, and then the mist has to evenly saturate the mucous membranes of your nostril. And — it has to land high enough to not drip out your nose so that you don’t  lose it and straight enough not to not run down the back of your throat. On top of that, it must be well-aimed enough to not get wasted on plain air and gentle enough to not get sneezed back out.

If that weren’t tricky enough, in addition to that, the ketamine spray delivers a mist that gives a concentrated dose over just a very few brief seconds of contact with mucous membranes, and just minutes of contact with critical and delicate brain systems … systems that need time to change for the better.

It’s just a bit too iffy …  whereas intravenous infusions are slow and precise and we can calculate, predict, and control.   They allow very slow, controlled exposure of critical pathways to a medicine that stimulates neuronal growth and rearborization.

IM Ketamine: The Problems with Timing and Side Effects

In the case of intramuscular, or IM injections, ketamine must enter the muscle then find its way to the blood vessels and be absorbed.

Because the muscles contain dense blood vessels, a large portion of the drug makes it to the blood stream, but not all.   There’s no way to determine how much time it will take the ketamine to leach out of the muscle, or how much of it will leach out, and reach your bloodstream so it can reach your brain.

From the time it’s injected, it depends on the circulation in that muscle and the condition of that muscle in terms of fitness.

To put it simply, your guess is as good as mine as to the total amount that makes it to the bloodstream and the rate at which it reaches the tissues in the brain to effect the changes we want to see.

Once again…way too iffy.

For ketamine, you need a route that ensures that ketamine reaches its target effectively, and you need a dose that will deliver the precise amount your brain needs to receive the optimum benefit from it. You also need it to reach the brain in a slow, controlled way.  It needs to work, not frighten.

Because that’s another problem we’ll talk about in a bit. SIde effects … they just can’t be controlled once the medicine is in the muscle.

Bioavailability Comparison

Take a look at the differences in bioavailability of ketamine through these different routes:

Intravenous    100%

Intramuscular    approximately 93%

Intranasal    approximately 45%

Sublingual    approximately 19-50%

Approximately??  For your brain??

As you can see, a range of 19-50%, as seen with sublingual use, is just far too uncertain.  And approximating the dose, as seen with IM and intranasal ketamine, especially when we’re seeing numbers as low as 45%, just isn’t the best way to ensure solid, safe, predictable benefits.

Exquisite IV Ketamine

But when the ideal low dose of ketamine is precisely measured and administered directly into your bloodstream by an intravenous infusion, you get the benefit of all its anxiety-smashing, depression-relieving qualities in full measure.

There is none lost through dripping, sneezing, swallowing, digestion — or sloppy spraying or poor coordination.  There’s just nothing getting in the way.

It’s a beautiful thing.

Add to that the fact that IV ketamine has been used in anesthesia since the early 1960’s.  It’s backed by decades of data confirming its bioavailability, safety, and tolerability.

Effectiveness

Now think about this:

When you take ibuprofen for a headache, how long do you expect to wait to experience relief?  30 minutes?  45?

Have you ever been given an IV medication in the hospital? If so, you know that you start to feel relief pretty quickly. It can be a lifesaver when you really need it.

That’s because medications given by IV are available to the body so quickly … faster than any other route. There’s some benefit almost immediately, and it continues until you feel better and better as  the medication circulates.  With IV ketamine, the benefits keep growing.

Another factor is that the physician should give ketamine at a controlled rate. This is to create certain conditions in the brain to trigger a waterfall of actions…like the proverbial falling dominoes… that relieve the symptoms of the psychiatric disorders we’re treating.

Ketamine Research

Ketamine for depression has been a topic of scientific and clinical study for some time. The best research on ketamine over the past few years for the treatment of suicidal thoughts, depression, bipolar depression, PTSD, and OCD has used very precise IV infusion protocols.

It’s IV ketamine which–over and over–has been so startlingly effective.  Intranasal sprays are being studied now, and one pharmaceutical company is sponsoring studies on a version of a ketamine spray it wants to turn into a brand-name patent, but there’s just not enough research on the spray technology, effective dose, or protocol for administering it to know what’s effective. One spray or two?  one nostril or two?  how strong?  exactly how much? and how often? every 10 minutes? or every 15? why not every day? twice a week?  

And intramuscular ketamine injections–forget about it.  They can be such a nightmare of erratic absorption and side effects that can persist for hours that there’s no clear way to judge what dose might be effective or tolerable for you.

But by giving ketamine IV, we’re able to give

• • the most precise dose (recalculated to a tenth of a milligram each time you lose or gain a pound)

• • the most precise rate (calculated down to the minute using sophisticated infusion pumps)

• a drug your body can utilize 100%

We create optimum conditions.  You experience the most benefits in the fastest way possible.  It’s a win-win.

Safety

Two words:  Side effects and drug abuse.  (OK, so it’s 4 words.)

We associate ketamine with potential side effects, no matter how it’s given. This is the case with the majority of medicines. But the range and severity and duration of those side effects vary tremendously depending on whether ketamine is given IV, IM or intranasally.

Keeping an Eye on Side Effects – Just in Case…

In an outpatient office setting, low dose IV ketamine infusions can be administered in a beautiful, comfortable environment.  High tech.  Soft touch.  Low lights and warm blankies (our patients love this!) with all of the medical monitoring and all of the important safeguards in place. Not the least of which is having a psychiatrist and infusion nurse right there to address any possible side effects.

In case of side effects, the psychiatrist can stop the infusion within seconds.Then she can administer a small dose of medication to treat the problem. Within minutes after the infusion, you can be ready for tea, snacks, conversation, and the ride home. 

This isn’t true with intramuscular ketamine. In this case the full dose is administered in about a minute instead of slowly over 45, and there is no way to stop or slow the absorption once it’s already been injected into the muscle.  And if strong dissociative side effects occur, as they often do with IM, the continued absorption of ketamine from the muscle can’t be interrupted– and the nightmare can last for hours.  In one report, patients were kept lying down for at least 4 hours after an IM injection of ketamine for depression…just for monitoring.

If you use an intranasal spray mist at home, you administer it to yourself. There is no physician right there to address side effects.

Preventing Abuse

Unfortunately, ketamine has been shanghai’d by those seeking illicit experiences. It’s not just necessary, it’s critical to guard the way it’s distributed. It’s a shame, but a fact of life in the world we live in.

Think about this: If patients have ketamine available as a nasal spray for “as needed” use, what’s the risk? Clearly, if ketamine spray is available at home, there’s a much higher risk of outright abuse, sharing, or sale on the street.

It’s just so clear:  right now, IV ketamine infusions are the best and most reliable approach we have. They allow precision dosing, instant responsiveness by the physician, almost-instant control of any potential side effects, and no risk of drug abuse or sharing in the community. .

At Innovative Psychiatry, we provide ketamine exclusively by IV infusion because it’s the best method for providing rapid, maximum benefits in the safest environment for you.

If you have not experienced relief from antidepressants, or if you’re tired of trying one thing after another,  give us a call and let’s work together to evaluate what might be more effective for you.

To the recovery of your best self,

Lori Calabrese, M.D.