August 17, 2022

Sublingual ketamine troches for home use: How clinicians can get started (part 2)

Written by

L. Alison McInnes, MD, MS

This is the second in a two-part series of articles from Dr. McInnes on sublingual ketamine troches for home use. The first article, “Sublingual ketamine troches for home use: An evidence-based introduction (Part 1),” can be read here.

Ketamine troches are having a heyday, driven by ease of access and use, relatively low cost, and convenience—for clinicians and patients.

Not to mention, targeted ads promote at-home ketamine use to consumers:

Image of two advertisements. First ad: Text: Take control of your mental health with peace of mind and prolonged clarity. Image: A hand holding up a ketamine troche with a pink background. Second ad: Text: I tried at-home ketamine for depression and anxiety with Mindbloom. Here's my experience. Image: A profile of a face surrounded by colorful clouds and nebulas.
Facebook Ads from Peak and Mindbloom

Given their rising popularity, clinicians need to have a realistic picture of sublingual  (SL) ketamine troches.

What does the efficacy data say?

In Part 1 of my “Sublingual ketamine troches for home use” series, I addressed efficacy and found that there is some evidence for the efficacy of oral/SL ketamine, although it would be considered low-grade at this time as the majority of the data is open-label.

I strongly encourage you to read a recent article by Swainson et al. 2022, “Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing.”  Dr. Jennifer Swainson is an Assistant Clinical Professor in the Department of Psychiatry at the University of Alberta Edmonton and has long been an advocate for oral/sublingual (SL) ketamine as a pragmatic approach to increasing access to care for patients with treatment-resistant depression. This article is the closest thing that we have to practice guidelines for oral/SL ketamine to date.  

Concerns with Sublingual Ketamine Troches for home use:

After efficacy, the second biggest concern clinicians have about this mode of treatment is about its abuse potential. Swainson et al. synthesized a lot of useful information about non-prescription ketamine misuse. They noted that the most commonly misused form of ketamine is a powder produced by dehydrating ketamine solution, which is usually insufflated or snorted, but has also been smoked or added to beverages. 

Doses may range up to several grams a day of ketamine in chronic users and they discuss the health consequences of this habit. In contrast, my compounding pharmacy told me that most prescriptions they receive for SL ketamine encompass doses of 50-300 mg up to thrice weekly with supplies given for 1-3 months. 

I note this to underscore that amounts of prescribed ketamine for medical use are generally a fraction of what folks buy for recreational use. Also of note is a comparative ranking of 20 substances with potential for misuse based on a review of the available literature by Nutt & colleagues 2007, who ranked ketamine sixth overall, on par with benzodiazepines and amphetamines. Keeping these concerns in mind, clinicians can take practical steps to ensure they and their patients are covered.

How can clinicians get started with providing sublingual ketamine troches as a form of therapy?

Here are some practical suggestions to consider, from my own experience as a psychiatrist and ketamine-assisted psychotherapy practitioner, as well as the Swainson & colleagues paper.

Inform your malpractice insurer.

Specifically, you’ll need to let them know that you will be prescribing troches for home use and have outlined your plan of care and rationale. Therapists need to be sure they have informed their malpractice insurer as well.

Consider taking a training course.

There are many reputable organizations that are well-versed in this particular method of administration. Some that I would recommend are Psychedelic Research & Training Institute (PRATI), Fluence, and Polaris Insight Center.

Have a robust plan for informed consent.

Some tips from personal experience:

  • In addition to a detailed treatment protocol including risks and benefits please be sure to state clearly that this treatment has not been FDA approved and is being used off-label for depression. 
  • Always make the goals of treatment explicit whether it be a 50% reduction of symptoms on a validated rating scale or other functional outcome. 
  • Always include an exit strategy.  If a patient starts to exhibit signs of possible misuse, or you have any concerns at all that the treatment is not having the desired effect, please protect yourself and the patient with clear language that outlines conditions for discontinuation of treatment. 
  • Advise patients to dose at night and not to drive until the next day after use.
  • Outline all possible side-effects of treatment including ketamine cystitis.

Limit the supply of Ketamine troches for home use.

Prescribe in limited quantities and think carefully about refills. Prescribing zero refills sends a message to the patient that you will be evaluating the efficacy of the treatment carefully (i.e. 2- to 4-week supply, depending on frequency of dosing). Do a Prescription Drug Monitoring Program (PDMP) check before initiating initial and repeat prescriptions. 

Document side effects.

It is prudent to observe the initial dosing session in office to monitor blood pressure, dissociation (i.e. with CADSS6, a shorter version of the CADSS), nausea, sedation, vertigo, anxiety, numbness, tingling and any other side-effects the patient might report. Careful documentation of side-effects at least in the early sessions and with dosage changes are critical for good med-legal protection. 

Patients should have a home blood pressure to monitor responses to changes in dosing. Please document that you have educated patients on dissociative symptoms in your note – use of the CADSS6 makes it easy to do this. During maintenance therapy you should also ask about the emergence of cystitis symptoms. 

Document efficacy.

The use of routine measurement-based care is always recommended but is especially important with at-home use to help the patient understand what success looks like. Documentation also provides you with data to justify cessation of treatment if it’s not working and protects you from a med-legal perspective. When you’re working with a medicine that has moderate abuse potential and limited efficacy data you must operate with the highest clinical standards. 

IV ketamine still has the most evidence to support longer-lasting effects. Here is a downloadable template to streamline your IV ketamine documentation.

Monitor for signs of misuse.

Red flags of misuse are similar to those with benzodiazepines or stimulants.  Lost prescriptions, requests for early refills, and repeated requests for dose escalation or increased frequency of dosing (despite stable mental health status) should be carefully evaluated. 

Proactive medical monitoring.

It’s a good idea to rule out medical causes of depression prior to treatment with a thyroid stimulating hormone and vitamin D level.

Document liver function tests (LFTs) to ensure that they’re not 2-3x higher than normal limits and consider repeating LFTs every 3 months.

Ketamine cystitis is often cited as a side effect of concern and I would advise clinicians to monitor proactively for this in a few ways:

  • Patients with depression have an elevated risk of interstitial cystitis (Cepeda et al. 2019) so be sure and get a history from your patient and determine whether or not they are sexually active and possibly at higher risk.
  • Women of childbearing years should be reminded to abstain from conception while they are taking ketamine and to use contraception if sexually active with a man.
  • Check a urinalysis at baseline and every 3–6 months for signs of microscopic hematuria. Encouraging the patient to be especially well-hydrated on dosing days is always a good idea. If a patient develops increased urinary frequency, urgency, or dysuria while taking the treatment, send them for a urinalysis right away. 


Before I close this post, I should make readers aware that I’m also on the Scientific Advisory Board for Clexio Biosciences, where I oversee their clinical trial of an oral esketamine pill for daily use. The pill has been engineered such that the esketamine cannot be extracted and diverted. I’ll share more about the results of their Phase 2b trial early next year in the Osmind blog. If all goes well, they will launch a Phase 3 trial in 2023 and clinicians may be able to refer patients at that time if interested.

About Dr. L. Alison McInnes:

Dr. L. Alison McInnes is Vice President, Medical Affairs at Osmind. She is a nationally recognized expert in psychiatry and mood and anxiety disorders, having specialized in treating refractory disease for over a decade. She is an expert in ketamine treatment and psychedelic medicine. McInnes founded and served as Medical Director for Kaiser Permanente's ketamine infusion therapy program for a number of years, and was previously an Associate Professor of Psychiatry at Mount Sinai School of Medicine for 8 years where she ran a lab in psychiatric genetics. She was also an adjunct clinical professor at UCSF.

Dr. McInnes is regularly invited to speak at national and international conferences and consults for biopharmaceutical companies working at the cutting edge of neuropsychiatry. She is a member of the American Society of Ketamine Physicians, Psychotherapists and Practitioners (ASKP3) Certification Governance Commission, which is an autonomous governing body that oversees the development, implementation, and management of a certification program for clinicians offering ketamine therapy. In her current clinical practice, she focuses on treatment-resistant mood disorders and complex cases.

Dr. McInnes received Bachelor’s and Master’s degrees from Stanford University and her MD from Columbia University. She completed her residency at UCSF and research at the VA Research Fellowship and Howard Hughes Physician Research Fellowship in Psychiatric Genetics at UCSF.

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