Ketamine Assisted Psychotherapy (Tamar-Mattis 5/29/2024)

 The link for the recording of this session is HERE.

***

Many thanks to Dr. Suegee Tamar-Mattis and Celeste Monette, LCSW for a really interesting Grand Rounds this week on the use of Ketamine Assisted Psychotherapy. Those of us in primary care know too well that our tools for managing mental illness -- treatment-resistant depression, suicidality, and PTSD, for example -- are terribly limited. Dr. Tamar-Mattis encouraged us to consider psychedelics as a powerful and increasingly evidence-based tool that may change patients' brains and lives. The use of psychedelics for mental health is not new, but it is quickly evolving.  It strikes me that was once considered "fringe" is now moving into the mainstream. 

As someone who has been practicing for over 15 years, one's willingness to take on something new is such an interesting concept in  medicine. Are you an early adopter? Or do you wait for the evidence to be convincing? Do you feel comfortable with experimentation? Or do you prefer engaging only in the "standard of care"? Why? Why not? 

My notes:

Dr. Tamar-Mattis opened their presentation with the new hope of psychedelic medicine -- this is not just prescribing medications, but the combination of psychedelics and therapy. That is, the use of ketamine to offer patients a novel window into their mental health that then allows them to engage in therapy in a productive way, thereby offering hope in an area that can otherwise feel hopeless.

Psychedelics have been shown to have impact on both neurogenesis and neuroplasticity in the brain, and it is their effects on neurons that may be key to why they work. In essence, psychedelics allows patients with deep neural pathways to rewire them and/or alter them by acting directly on the neuronal networks. This concept is often referred to as "the snow globe effect" -- that is, for many people with severe mental health issues, the neuronal pathways are fixed and, therefore, deeply carved in the metaphysical snow; thus, it is virtually impossible for patients to forge a new path. BUT, with the use of psychedelics, the snow globe (neuronal networks) is virtually "shaken up" and the fixed pathway is then uncarved, opening the possibility for patients to create a new pathway, a healthier one. 

I love this concept for patients -- particularly for those who seem so stuck. And it is the very stuck patients that get most frustrated with us (providers and healthcare system) and are most frustrating to their clinicians.

***
Ketamine is the only legal psychedelic at the federal level. There is evidence it works to improve mental health, even for patients who are already on SSRIs. It has a rapid anti-depressant effect and a rapid anti-suicidal effect. There is increasing evidence -- albeit small studies-- that it can positively impact PTSD, OCD, eating disorders, anxiety, some addiction, treatment-resistant depression and suicidality. In addition, there has been some use in developmental trauma and end of life issues. 

For specific studies and data on the use of ketamine for psychiatric disease, see the reference list below**, which was compiled by Dr. Tamar Mattis.

Psychiatric contraindications: active mania in Bipolar I disorder, psychotic disorders, some personality disorders (particularly if very rigid or very unorganized)

Medical contraindications: heart disease (particularly recent MI or new CAD), uncontrolled hypertension, liver disease (ketamine is metabolized in the liver), pregnancy, increased intra-cranial pressure, and oxygen dependence (due to risk of respiratory depression). 

Side effects: regularly elevates BP 10-20mm Hg, nausea and vomiting (can pre-treat with ondansetron), respiratory depression (rare at doses used for treatment).

***
Ketamine cannot be absorbed orally. But can be delivered via 

• Lozenges/troches
• Nasal spray
• IV
• Injection (subcutaneous)

The most controlled way to administer ketamine is via subcutaneous injections (starting doses in their clinic is 0.5-1.5 mg/kg (sometimes as high as 2.0 mg/kg), well below the anesthetic dosage ranges, which begin at 6mg/kg). Ketamine's acute effect lasts between 30-45 minutes. As used by Dr. Tamar-Mattis in the clinic, these visits are generally 2.5 hours long, allowing for time to recover from acute effects as well as concomitant psychotherapy. Patients wear masks, and music is played. A typical treatment time is 6 sessions (or 2 months total), again well-below standard years of psychotherapy for intractable mental illness.

It is believed that completing therapy in the altered state allows a shift from intellectual ideas (e.g. suicidality, severe depression) to a "felt-experience". Also, while ketamine is considered a dissociative anesthetic, this is not a dissociated psychological experience. It is more in the body. The work is labor intensive not because of the drug-administration but rather due to the psychotherapist constant presence during the entire session-- which is costly.

Group ketamine-assisted psychotherapy, which the clinic is currently experimenting with, offers the possibility of increased connection, community, and lower cost -- making it more affordable to the wider audience, particularly to vulnerable populations.

As Dr. Tamar-Mattis herself expressed, "We are living in the Wild West of Ketamine right now"-- patients can even order ketamine online to self-administer. She cautioned against the use of ketamine without the assistance of trained providers, mostly to help support patients through the important work of the therapy. Most of their patients have outside therapists, and they consider the work they do at the clinic an adjunct to the psychotherapy patients are already undergoing. Barriers to care include cost: there is not insurance coverage for this type of treatment, and a full course of treatment can cost between $6000-8000 out of pocket, as well as stigma. 

Dr. Tamar-Matti's clinic, Liminal Medicine, in Sebastopol is offering a one-time experiential class for healthcare providers (including physicians, mental health providers) on Saturday June 22, as well as a 5-week caregiver group, titled "Helping the Helpers". See below for details.

 **

References
Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. April 1, 2018 https://pubmed.ncbi.nlm.nih.gov/29202655/

Ballard ED, Yarrington JS, Farmer CA, Richards E, Machado-Vieira R, Kadriu B, Niciu MJ, Yuan P, Park L, Zarate CA Jr. Characterizing the course of suicidal ideation response to ketamine. J Affect Disord. December 1, 2018 https://pubmed.ncbi.nlm.nih.gov/30099268/

McInnes, L. A., Qian, J. J., Gargeya, R. S., DeBattista, C; Heifets, B. D. (2022, January 11). A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. Journal of Affective Disorders. Retrieved May 10, 2022, from https://www.sciencedirect.com/science/article/pii/S0165032721014142#sec0007

Witt K, Potts J, Hubers A, Grunebaum MF, Murrough JW, Loo C, Cipriani A, Hawton K. Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials. Aust N Z J Psychiatry. May 14, 2020 https://pubmed.ncbi.nlm.nih.gov/31729893/

John G. Keilp, PhD; Sean P. Madden,; Julia E. Marver, PhD; Abigail Frawley, PhD; Ainsley K. Burke, PhD; Mohammad M. Herzallah, PhD Mark Gluck, PhD; J. John Mann, MD; and Michael F. Grunebaum: Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation. The Journal of Clinical Psychiatry. November 2, 2021.
https://www.psychiatrist.com/jcp/depression/ketamine-neurocognition-patients-with-suicidal-ideation/

The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
Samuel T. Wilkinson, M.D., Elizabeth D. Ballard, Ph.D., Michael H. Bloch, M.D., M.S., Sanjay J. Mathew, M.D., James W. Murrough, M.D., Ph.D., Adriana Feder, M.D., Peter Sos, M.D., Ph.D., Gang Wang, M.D., Carlos A. Zarate Jr., M.D., Gerard Sanacora, M.D., Ph.D. Published Online:3 Oct 2017https://doi.org/10.1176/appi.ajp.2017.17040472

Jollant F, Colle R, Nguyen TML, et al. Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review. Therapeutic Advances in Psychopharmacology. 2023;13. doi:10.1177/20451253231151327 https://journals.sagepub.com/doi/10.1177/0004867419883341

Anzolin AP, Goularte JF, Pinto JV, Belmonte-de-Abreu P, Cruz LN, Cordova VHS, Magalhaes LS, Rosa AR, Cereser KM, Kauer-Sant'Anna M. Ketamine study: Protocol for naturalistic prospective multicenter study on subcutaneous ketamine infusion in depressed patients with active suicidal ideation. Front Psychiatry. 2023 Mar 9;14:1147298. doi: 10.3389/fpsyt.2023.1147298. PMID: 36970275; PMCID: PMC10033666.

Ahmed GK, Elserogy YM, Elfadl GMA, Ghada Abdelsalam K, Ali MA. Antidepressant and anti-suicidal effects of ketamine in treatment-resistant depression associated with psychiatric and personality comorbidities: A double-blind randomized trial. J Affect Disord. 2023 Mar 15;325:127-134. doi: 10.1016/j.jad.2023.01.005. Epub 2023 Jan 7. PMID: 36623562.

Chen, C. C., Zhou, N., Hu, N., Feng, J. G., & Wang, X. B. (2023). Acute Effects of Intravenous Sub-Anesthetic Doses of Ketamine and Intranasal Inhaled Esketamine on Suicidal Ideation: A Systematic Review and Meta-Analysis. Neuropsychiatric Disease and Treatment, 19, 587–599. https://doi.org/10.2147/NDT.S401032

Gender Affirming Care (Beal, 5/15/2024)

Due to concerns about safety, there is not a public recording of this session. If you would like a private link to view the session, please email Veronica Jordan at jordanv@sutterhealth.org. The link will be good for about 6-8 weeks. 

***

My notes:

• Flatten the power dynamic, flip the power
• "You can call me Dr. Beal, Dr. Crystal, or Crystal. I use they/them pronouns. What would you like me to call you?"
• Be person-centered, trauma informed and culturally humble
• Ask patients what they want for their body
• Gender identity should not be conflated with goals of care
• Individualize gender affirming care based on what the patient wants/needs (see image of the table patients pre-fill out prior to visits).

Now, onto the nitty gritty:

1) If a patient wants limited physical changes and/or more of an emotional experience. . . consider simply low dose hormones (estradiol 0.5mg daily to start, very low dose for someone desiring more estrogen, testosterone 5-10mg IM weekly, also very low). If for some reason, low dose hormones are not desirable, you can also consider anti-androgens only or selective estrogen modifiers (SERMS) only. 

2) If a patient wants hair loss treatment, reduction or prevention. . .particularly in someone with a family history down the maternal line OR someone who has anxiety about potential hair loss with hormone treatment -- consider low-dose oral minoxidil (LDOM) 2.5-5mg/day. This is well tolerated, can cause more body hair in other places. Of note, topical minoxidil is toxic to pets. Finasteride has been associated with SI and can slow changes from testosterone so may be a less desirable. Estrogen protects head hair, so don't have to worry about this in patients on systemic estrogen. Other options include tattoos, make up. Of note, a lot of patients take biotin (a supplement which is thought to strengthen and increase hair growth); unfortunately, biotin can artificially elevate estrogen, so have patients stop 72 hours before having their labs drawn.

3) If a patient wants more/thicker facial hair. . .first, set reasonable expectations. It will take at least 6 months to notice change and maybe up to 10 years (!!!). Facial hair growth is a slow, gradual process. And depending on your family history, you may not be able to grow a ton. Topical minoxidil may speed the transition from peach fuzz to a full beard, but it's still low. Remember, it's toxic to pets. Also, it can be irritating to skin, so patients should try to apply daily but may need to space out depending on skin irritation side effect. Also consider micro-needling with ink and make up as alternate options.

4) If a patient wants bottom growth (i.e. clitoral enlargement). . .DHT (dihydrotestosterone) is not available in the US. Practitioners in the US tend to use 10% testosterone cream (compounded) daily at first, then weekly x 6 months. Dr. Beal notes that topical testosterone is always transdermal (i.e. some portion is absorbed).Alternatively, can use testosterone oil for injection>> it comes in 1ml supply, can apply 0.05 to 0.1ml topical to genitals. Of note, topical hormones can definitely transfer to partners and should be washed off prior to contact.  Androgel should not be used on the genitals because it contains alcohol and can significantly burn genitals. 

5) If a patient has a uterus and/or breasts and wants to prevent menses and/or slow/stop breast development. . .consider SERMS, specifically Raloxifene is the SERM of choice (tamoxifen is another option but has more side effects and probably less safe over time). Raloxifene rx is 60-120 mg/day. Can be taken indefinitely. Does also have bone marrow density protection. 

6) If a patient wants to optimize breast development. . .again, important to set realistic expectations. Most trans people will not achieve larger than an A cup. There is some evidence for transdermal progesterone cream compounded 25mg/ml 1/2 ml pump daily. Some patients love it and feel like it makes a big difference, others do not. Of note, when starting estrogen, lower and slower estrogen dosing tends to help boost breast development. Of second note, there is a theoretical increase in breast cancer risk with progesterone, no data to support or refute that at this time.

7) If a patient has persistent bleeding. . .consider depo provera injections.

8) If a patient has painful erections. . .If the goal is to have continued erections (but make them less painful), you can use tadalafil or TD testosterone. If goal is to prevent erections, use more aggressive testosterone dosing/supplementation. 

Common gender affirming procedures

• filler injections
• botox injections 

Both are temporary and can make changes to brow, jaw, cheeks, lips. Allow people to experiment with changes before opting for something more permanent (surgery). 

• Hair removal
• Liposuction/lipo-sculpting
• Implants

In response to an audience question, Dr. Beal spoke a bit about the unique experience of each individual's response to medical interventions. It is very personal and unique. For many people, hormonal treatment have some emotional effects. These effects may or may not be desirable for each patients. With testosterone, people describe their emotional experience as "more simple", less crying, more irritability and impatience, less access to empathy. With estrogen, people tend to describe the opposite set of effects: a more complex emotional experience with increased lability, increased crying frequency and even increased access to empathy.

In summary, Dr. Beal recommends whenever you are initiating treatment, starting low and going slow. Allow the patient to guide you in their experience of the intervention and have some power over next steps. 

There are tons of resources on Dr. Beal's clinic website: https://www.queercme.com/blog

Specifically a blog post on testosterone and singing: https://www.queercme.com/blog/testosterone-and-singing

Medical ethics of AI (Feldman 5/8/2024)

 You tube link HERE.

A summary of this presentation is forthcoming. Please check back. 

To understand and to be understood: language interpretation in medicine (Slater, 5/1/2034)

Many thanks to Dr. Allison Slater, our final resident from the class of 2024 to give her senior Grand Rounds presentation this week. She gave a really important and thought-provoking presentation on language and language interpretation in medicine. It was titled "To Understand and be Understood", a title she borrowed from a March 2017 AMA Journal of Ethics that focused on language, literacy and hierarchy in medicine.  

A recording of her presentation can be found HERE.

My notes:

Dr. Slater began with a review of words:

• interpretation: spoken language being repeated in an alternate language
• translation: written language being repeated in an alternate language

The distinction between the two is important because trained interpreters have special training and skill in being able to perform live and capture the meaning of the discussion, whereas written translators have the tincture of time and the ability to be more precise. In the healthcare setting, we are generally using live interpretation with patients during patient encounters, though document translation is also important issue, particularly with regards to clinic after visit summaries and hospital discharge summaries.

• limited English proficiency (LEP): US Census distinction based on an individual's response to the question: "How well do you speak/read/write English".  LEP is considered anyone who responds anything other than "very well"
• Non-English language preference: upon closer examination, the term LEP is a "deficit-oriented" distinction and in no way recognizes a person's proficiency in languages other than English. Thus, this may be the preferred term. 

Professional interpretation in the healthcare setting is the law. 

This legal protection comes through various acts and executive orders, but which has not always been accepted:

• 1964: Civil Rights Act codifies "national" origin as a protected class for all programs or activities receiving federal funds
• 2000: President Bill Clinton signs an executive order designed to improve access to services for patients with limited English proficiency (LEP) from all federally-funded agencies
• 2003: AMA president makes public statement that he sees "no need for professional interpreters"
• 2010: The Affordable Care Act (aka ACA/Obamacare) added protections for patients, including regulation around signage in 15 top languages for each state
• 2019: Trump rolls back and narrows protection
• April 26, 2024 (last week!): a federal appeals court reinstates the 2010 ACA protections that had been repealed in 2019

Despite the regulation requiring healthcare institutions to provide no-cost language interpretation for patients with non-English preference (and the real risk of malpractice vulnerability) we are al aware that what happens in real life is not always what should happen. Many healthcare providers "get by" with inadequate language skills, physicians in particular are well-documented to overestimate their language skills, and patients with LEP are known to have more adverse outcomes, longer hospital length of stay, have more tests, higher rates of readmission, and feel discriminated against in the places they are receiving health care.

Unfortunately, ad hoc or informal interpretation is often used -- including patient family members and/or non-trained staff. Ad-hoc interpreters -- i.e. anyone who isn't trained and certified-- introduce a range of possible challenges: the potential for role confusion, may not have adequate language abilities for the content, insufficient attention and recall, not following standard interpretation protocols, subjectivity and biased interpretation, breach of confidentiality, missed conversations, and the possibility of limited scope of inquiry (e.g. intimate sexual issues). In fact, one study found that 1/4 to 1/2 of questions asked by a clinician were misinterpreted or omitted by ad hoc interpreters

While "routine conversation" between LEP patients and clinicians who self-identify as being language proficient may be acceptable, clinicians should really be subject to a proficiency certification to ensure that vital medical conversations (e.g. diagnosis, surgery plans, medical treatment plans, procedural consents, and discharge plans) are correctly communicated. Medical communication requires precision -- and this is even more important with sensitive topics, e.g. mental health, options counseling, substance abuse, trauma, and sexual assault. 

In addition, official interpreter roles can include exploration and explanation of culturally relevant features of a conversation. 

Okay, deep breath. As I myself said at the end of her presentation, there are many ways in which much of what Dr. Slater shared has me feeling bad about myself. Even as someone who considers herself a champion for the best care for our patients with LEP, I often find myself acting badly: acting as an interpreter (myself without formal training), using family members for interpretation (twice in the last 2 weeks, interpreters in patient's preferred language were not readily available), failing to give an interpreter context, not ensuring that every person in the room has access to the same information.

Let's do better!
Best practices, my favorites: 1) Make sure you allow extra time 2) Always write down the ID# of the interpreter you are using 3) huddle with the interpreter before the conversation whenever possible 4) look for red flags (e.g. confusing answers, confusing questions, long statements that are not being appropriately interpreted) and 5) if you don't use an interpreter, document why. For more, see the Table below from the 2014 AAFP article, Appropriate Use of Medical Interpreters