Lozenges are an alternative method to intravenous (IV) or intramuscular (IM) injections. They come in two forms: troches (pronounced “tro-Keys”) and rapid-desolving tablets (RDTs) Below, we discuss the benefits, concerns, dosing, and bioavailability of troche and RDT administration of therapeutic ketamine.
Benefits:
- Non-invasive: lozenge administration is non-invasive, which may be more acceptable to patients uncomfortable with IVs or injections.
- Ease of administration: lozenges are simple and easy to administer, requiring no assistance from healthcare professionals.
- Home use: Patients can self-administered lozenges, enabling treatment in the comfort of their homes.
Concerns:
- Lower bioavailability: the sublingual route of administration has lower bioavailability than IM and IV administration, as the ketamine undergoes first-pass metabolism in the stomach and liver. Consequently, higher doses are necessary to achieve therapeutic effects (1).
- Variable absorption: Due to factors such as oral pH, saliva production, and individual variability, absorption can be inconsistent, leading to unpredictable therapeutic effects (2). Bioavailability is quoted in a wide range of 25 – 30%. Sometimes the lower end of the range is quoted at 20% or even 16%. The high end of the range is rarely quoted much above 30%.
- Slower onset of action: Troche and RDT administration typically have a slower onset of action than IM and IV routes, which may not be suitable for acute treatment or rapid symptom relief (3).
- Taste: Ketamine is bitter, which may be unpleasant for some patients when using troche or RDT formulations.
- Dosing and Bioavailability:
- The dosing of ketamine troche and RDTs depends on the indication and patient population. For mental health patients, doses can range from 50 to 200 mg, or can go much higher depending on tolerance and the depth of session desired. Joyous begins dosing at quantities as low as 15 mg. (4, 5). The dosing frequency depends on the patient’s response and the clinician’s guidance. Mainstream dosing frequency is every three days or twice a week. Some patients do better on alternate-day dosing. A few benefit from daily dosing. Joyous is an exception as they only dose daily. On maintenance, sublingual dosing intervals can stretch to weekly or alternate weeks.
- The bioavailability of ketamine through oral and sublingual routes is considerably lower than that of IM or IV administration, ranging from 17-24% for oral and 25 – 30% for sublingual administration (1, 6). This reduced bioavailability requires higher doses to achieve therapeutic effects.
Lozenges seem to be a lot like pills and patients are accustomed to swallowing pills. Do not swallow your ketamine lozenges! There are two reasons to avoid swallowing lozenges. First, some patient’s stomachs find ketamine disagreeable. If you swallow a whole lozenge you are vulnerable to having a very upset stomach; much more so than if you swallow the little ketamine in your saliva after allowing most of the drug to be absorbed sublingually. Second, the bioavailability of swallowed ketamine is so much lower that you will under-dose yourself by swallowing.
Many patients complain about the taste of lozenges. Some don’t like the taste but tolerate them. Others can’t tolerate the taste at all.
Compounding pharmacies often cater to the taste objection by offering alternative flavorings in their products. Sometimes a patient discovers a flavor he tolerates better than others. But this is not an altogether satisfactory approach. The patient will get his first order of lozenges with, say, apple flavoring and is stuck with that flavor for the first month, whether he likes it or not. The next month, he might ask for berry, and is stuck with that flavor for the second month. The third month, he might ask for cherry, and so forth.
If you can’t tolerate the taste of lozenges, the next alternative to try is the rectal ROA. Taste is not an issue. You can ask your provider to prescribe suppositories. This formulation may be more expensive than lozenges, so ask your compounding pharmacy for comparative prices.
You can also insert an RDT whole in the anus. Or, alternatively, crush an RDT, dissolve it in water, and inject it using a syringe. Amazon sells suppository applicators and syringes without needles suitable for this purpose.
Providers generally recommend that patients hold lozenges in their mouths for 15 – 20 – 30 minutes, minimizing swallowing their saliva. (Mindbloom is a notable exception. They have patients hold the lozenge for only 7 minutes.) If the patient can’t tolerate the taste of ketamine, he may have trouble reaching even the 15-minute target and won’t hold out for 20 minutes.
Most of the ketamine is absorbed in the first minutes of holding the lozenge in the mouth, and then the rate of absorption tapers off rapidly. Accordingly, if the patient can hold a lozenge for only 15 minutes, it’s not a disaster. Twenty minutes would be better. Thirty minutes a bit better. Not much to gain by holding for 45 minutes and almost nothing to be gained by holding out for 60 minutes.
Initially, ketamine will cause the mouth to produce a lot of saliva.
Whether taste or excessive saliva is a problem initially, it tends to dissipate over the first few doses and is less of a problem. In any case, the saliva has to go somewhere eventually: to spit? Or to swallow?
Most sublingual patients eventually swallow their saliva. Note that while the bioavailability of swallowed ketamine is markedly lower than ketamine absorbed sublingually, it’s not zero. Suppose your sublingual dose is 100 mg. And suppose that your bioavailability is 25%. You would eventually absorb 25 mg of ketamine sublingually if you held your saliva for a very long time. But you won’t hold your saliva indefinitely. Suppose you swallow after 30 minutes and suppose you only absorb 75% of those 25 mg in those 30 minutes. You will swallow the remaining 25% * 25 mg = 6.25 mg of ketamine. The bioavailability of the swallowed ketamine might be as little as half the sublingual bioavailability. So, your stomach will still deliver 3.125 mg of ketamine to your bloodstream. You have lost only 3.125 mg of the 25 mg that you might have absorbed sublingually if you held your saliva for a very long time. These figures are merely illustrative. They show how the math probably works out to make swallowing less of a loss than it might seem.
Some patient’s stomachs get upset from swallowing their saliva. They prefer to spit. That’s fine. Not much of a loss as illustrated by the previous paragraph.
A ketamine-naive patient would do well to keep a shot glass at bedside during the first month of dosing. And also, for the first month of each titration to a larger dose. If the dissociative effects of the dose become overwhelming, spit your saliva into the shot glass and wait for your side effects to disappate. Then, pour the saliva from the shot glass back into your mouth to resume your full dose. Simply knowing you have the option to spit will reduce your anxiety about dissociation. When you spit you will know that in a few minutes, your side-effects are apt to subside.
As mentioned above, Mindbloom’s protocol is a notable exception. They prescribe remarkably large doses. However, they instruct their patients to spit after holding the lozenge for 7 minutes. Reportedly, the absorption of ketamine in these 7 minutes is about 10%.
It’s very important to carefully follow these spitting instructions if you are a Mindbloom patient, particularly as a ketamine-naive patient. If you hold your saliva much longer than the 7 minutes you will be in for the ride-of-your-life. And, of course, you must not swallow because the remaining ketamine in your saliva will still have considerable bioavailability when processed by your stomach.
A highly beneficial aspect of lozenges is that they can be broken into fractions by the patient. A ketamine-naive patient can slowly titrate herself over the first few doses. Joyous does this very slowly, instructing patients to break up their troches into doses as small as 15 then 30 mg.
Other providers will prescribe, e.g., ten lozenges of 200 mg for the first month. The patient may be instructed to break the first lozenge in half and take the first two doses at just 100 mg. The remaining 9 doses for the month are at 200 mg. In such a scenario the patient is free to break the first two lozenges in half and begin his ketamine journey with 4 initial doses of 100 mg.
Patients taking psychotherapy at-home via tele-therapy can also do ketamine-assisted psychotherapy using small doses. Break up lozenges and take a small dose about 20 minutes before the beginning of the session. Ask your provider to prescribe a couple extra lozenges each month for this purpose. Suppose your normal prescription is 200 mg 10 times a month. Take these 200 mg doses every three days. Ask for an extra 2 doses which you break into 4 fractional doses of 50 mg. Take these doses at each of your four weekly psychotherapy sessions.
The advantages of sublingual ketamine administration are – on balance – so significant that it is growing to be a very popular alternative to the traditional IV and IM ROAs. The convenience and lower cost of at-home administration are compelling considerations. The ability to titrate slowly under your personal control is also significant.
Taste is the most frequent objection. If you can’t accustom yourself to the taste the rectal ROA is your next best alternative. That’s followed by the nasal ROA.