Ketamine Delivery methods in Ketamine Therapy

 

Ketamine infusions

The delivery method of Ketamine is extremely important. Although the drug has no known lethal dose, overdose is still a bad event as it can cause possibly nightmarish hallucinations, where a patient could potentially harm themselves or others. A patient could possibly become incontinent as well - not a desirable outcome. To avoid this, control over the blood level should be tightly controlled. This is why a computer-controlled IV pump is the gold standard.

IV administration comes with its own list of risks and complications.  These include infection, hematoma, that is, continued bleeding from the vein under the skin after either ‘spearing’ the vein through when attempting to place the IV or later after removing a properly placed catheter from a vein that continues bleeding. IV’s can be inadvertently disconnected with subsequent blood loss, infiltration can occur (where medicine is infused into the subcutaneous tissue instead of into the vein), and more rarely blood clots, nerve damage and thrombophlebitis.

Some patients are terrified of needles. Causing massive anxiety just prior to giving Ketamine is not a great idea since the drug is a hallucinogen and tends to ‘magnify’ the emotional state of the patient.

Veins are precious. There is a growing awareness in the medical profession that ‘veins are precious’. Huge numbers of patients are presenting in hospitals who have had multiple hospital admissions and thus multiple vein sticks, whose peripheral veins are now extremely fragile and limited. Any technique that can preserve the veins in these patients is highly valuable. This goes double for any patient with a history of IV drug abuse.

 

Nebulized Ketamine (NebKet)

 

Infusions or NebKet? >

Delivery of Ketamine via a Nebulizer with a mask provides good control of Ketamine blood level. Absorption through the lungs is rapid and consistent. This obviates the need for an IV permitting self-administration.

This method shows great promise as it delivers a reasonably reliable dosage to the patient as breathing is typically regular over time and absorption approaches 100% from the lungs.  Insofar as the techinique permits self-adminstration with a high degree of safety, it may be possible to either replace the IV technique or at least provide for booster treatments a fraction of the price (possible 10-20 fold price reduction). It is important to use a free standing Nebulizer, not a hand-held variety.

Nebulization provides a remarkably consistent and predictable administration rate, while avoiding the disadvantages of the IV technique. The procedure has a huge safety margin compared to other methods, including IV infusion.  All other methods can lead to a scenario in which the entire dose is delivered at once, a highly undesirable outcome even if rare. There is a high safety window as the Nebulizer can be switched off or the mask removed by the patient. 

NebKet has the potential to be not just an adjunct (e.g. for boosters) but actually substitute for the IV approach in the initial series.

 

FAQ on Nebulized Ketamine >

STEP-BY-STEP INSTRUCTIONS >

Dr. Brian Stanton article on NebKet >

 

Intranasal spray

There is no support for the effectiveness- In March 2018, Australian researchers at the Black Dog Institute completed a pilot study for a ketamine nasal spray with unsuccessful results. Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses less than 100 mg ketamine.

The Intranasal spray is an inexpensive method, but the rate of absorption is all over the map, and there is relatively little control over dosing.  On the plus side, a patient is unlikely to overdose with this technique; they are more at risk of underdosing or just not consistently dosing.  There is little evidence in the literature to support the effectiveness of the intranasal approach.

The Intranasal spray is a decent method that has the virtue of allowing patient self-administration but suffers from significant flaws. Absorption from the nasal mucosa is all over the map, irritation of the mucosa from frequent spraying results in nasal congestion and venoconstriction, resulting in highly limited absorption, plus the patient must hold the sprayer to their nose, squeeze it and inhale nasally at a consistent rate, which gets progressively more difficult as the sedation sets in.

Nasal method depends heavily on the patient learning how to deliver a steady dose while becoming sedated. Most are probably underdosing, and many are developing a somewhat addicting habit which is not conducive to improving their overall health.

 

Esketamine nasal spray

Being rushed through critical reviews, Esketamine was approved by the FDA in March 2019. Janssen, part of Johnson & Johnson, has patented a version of ketamine called Esketamine that doctors would be able to give their patients through the nose.

Spravato is a reformulation of “party drug” ketamine. After the FDA fast-tracked approval of Esketamine in March 2019, Janssen can sell a very low cost drug for almost $800 per dose.

Currently, its wholesale acquisition cost stands between $590 and $885 per treatment session. Costs for the first month of treatment, which includes two sessions per week, could range from $4,720 to $6,785.

“The effectiveness data weren’t particularly good,” said Diana Zuckerman, president of the National Center for Health Research, a nonpartisan institute that studies science and health in Washington. “Especially for men and people over 65, and that’s mostly who the VA serves.”

Oral ingestion and Intramuscular injections

Oral ingestion, lozenges, and especially IM injection have very little dosing control, as there is no opportunity to titrate, and put the patient at significant risk of overdosage, with its attendant risks.  These methods should not be used and border on malpractice.

Sublingual administration of Ketamine (putting it under the tongue) also suffers from wildly variable absorption rates as do Oral administration and Intramuscular (injecting it into a muscle). Variable absorption means considerable risk that the patient will either get too little over too long a time (leaving the patient only mildly affected over many hours) and therefore not get the therapeutic effect or far worse, they run the risk of getting all the drug at once and experience a 'bad trip'.

IM (intramuscular) is an especially egregious method touted at some clinics, strictly for the convenience of the staff, and might be considered as malpractice. Inadvertant IV injection while attempting IM injection is serious risk.

There is a therapeutic window where the patient experiences an intense effect from the Ketamine without crossing into dissociation that seems to produce the most benefit. Many patients who are being treated with oral and IM are being repeatedly underdosed, and may not gain the true benefit available. Trying to get into that window with oral and IM would be quite risky since these techniques can't be titrated.

The ataxia of Ketamine resembles alcohol intoxication, and it is least disruptive to patients lives to arrange a 2 hour period where they are treated, possibly in their own homes, fully recover and get back to their daily routines as quickly as possible, rather than being mildly impaired for prolonged periods of time.

 

Patches and electrical skin patches

As for patches and electrical skin patches, these devices use special patches and/or electrophoresis to deliver a drug through a skin patch. The devices are expensive and I do not have the impression that they deliver a sufficient therapeutic dose in the case of Ketamine, but rather appear to deliver subtherapeutic dosages continually over a period of days. This medium is typically used for and is more suited to delivery of birth control medications, pain medicines, and anti smoking drugs where low doses delivered essentially continually are required. Some clinics are using them to treat patients with Chronic Regional Pain Syndromes (CRPS).

 

How do I know that I get the greatest therapeutic benefit?

For psychiatric conditions-

Based on observations and conversations with the patients, there is a theory that the greatest therapeutic benefit comes when the patients attain what can be called "the sweet spot." This is a blood level where the patients have an intense experience, i.e. they are slurring their speech, quite ataxic and many experience strong emotions, some sobbing at times. The key is to make certain that they do not get a blood level sufficient to induce 'dissociation' at which point they are completely anesthetized, unaware of their surroundings and unable to respond to command.

 

How success of ketamine infusion therapy can be measured?

Several techniques are being used to measure efficacy of ketamine treatment. Pain and depression are both subjective phenomenon, and a qualitative and objective instrument must be used in order to assess therapeutic efficacy. The following are some of the pain scoring systems and depression evaluation methods that are routinely being used:

 

Pain assessment scales-

- Visual Analog Scale (VAS)

- Wong-Baker FACES Pain Rating Scale

- 0–10 Numeric Pain Rating Scale

- Pain Quality Assessment Scale

 

Relief of depression-

- Beck Depression Inventory (BDI)

- Montgomery-Asberg Depression Rating Scale (MADRS)

- Hamilton Depression Rating Scale (HAM-D)

 

end faq