Indications for ketamine
Originally ketamine therapy was reserved for individuals with treatment-resistant disorders, although ketamine is now seen as an early option for those who do not wish to start traditional antidepressants. This allows for avoidance of potential toxic side effects associated with traditional anti-depressants such as decreased libido, weight gain, sleep and mood disturbances.
Depression
- After a single infusion of ketamine, the response rate is 71% at day 1 (peak anti-depressant effects at 24hr) and 54% at day 3
- Remission rate of 51% reported for depression
- The mean duration to relapse from another depressive episode is 17 days after a single infusion of ketamine — multiple infusions such as series of six prolong duration between recurrent depressive episodes
- There is a dose dependent relationship of anti-depressant effects
Anxiety
- Individuals with anxiety disorder most often have comorbid depression, thus treatment with ketamine can be helpful for both conditions
PTSD
- Lifetime incidence of PTSD is 6.8% or 12.9% among U.S. veterans
- Remission rates of upwards to 80% have been reported with repeated infusions over a short period of time for PTSD (six infusions over a 12-day period)
Suicide
- 3rd most common cause of mortality worldwide in ages 15–44
- Single dose of ketamine reduced suicidal ideation (SI) by 55% in 24hr, 60% still free of SI at one week post infusion, compared to other methods of acute suicide treatment such as electroconvulsive therapy (ECT) — 38% free of SI after three treatments
Addiction, alcoholism, and substance abuse
- In this clinical trial, patients who were treated with three weekly ketamine treatments had significantly more days abstinent from alcohol compared to the placebo group at 6-month follow-up; 86% of participated were sober after 6 months
- UPDATE DEC 2022: Researchers in England are launching a phase 3 clinical trial to determine the effectiveness of ketamine to help treat alcohol use disorder
- Innerbloom Ketamine Therapy has helped a number of patients with alcohol abuse and has had success helping patients stay sober and develop a new relationship with alcohol
Fibromyalgia and chronic pain
- May require longer duration infusions (2+ hours)
- In a double-blind, placebo-controlled study patients with fibromyalgia received a single dose of ketamine infusion (0.3 mg/kg), patients experienced a significant reduction (>50%) in pain intensity scores
- Ketamine has been known to have anti-inflammatory effects, with inflammation believing to play a big role in the pathogenesis of fibromyalgia and pain
Who should not get ketamine
- Uncontrolled hypertension
- Unstable heart disease (congestive heart failure, unstable coronary artery disease, history of arrhythmias)
- Uncontrolled thyroid disease such as hyperthyroidism given concern of tachycardia and arrhythmias
- Active substance abuse
- Active manic phase of bipolar disorder or schizophrenia
Mechanism of action of ketamine
- Ketamine acts as a non-competitive antagonist at the NMDA receptor, which means that rather than competing for glutamate binding site on the NMDA receptor, ketamine inhibits receptor function by blocking the ion channel itself, preventing influx of ions and thus activation/intracellular signaling
- Increases level of brain derived neurotrophic factor (BDNF), a protein that plays an important role in neurogenesis, causing regrowth and strengthening of broken connections in stressed brains
- Anti-inflammatory effects: Ketamine has been shown to reduce pro-inflammatory molecules such as the Tumor Necrosis factor TNF-α) that plays a role in a number of auto-immune disorders such as rheumatoid arthritis, inflammatory bowel disease (e.g., Crohn disease), ankylosing spondylitis, and psoriasis
The ketamine infusion experience
It’s important to understand that the healing process and antidepressant effects occur after infusions; the dissociative state/ “trip” is simply part of the process.
Some individuals find meaning in their ketamine experiences with things being brought up to the surface, which offers them something to work with internally or with a therapist. Others will have an experience filled with random thoughts and imagery that is difficult to understand. Individuals are reassured that it’s OK to have unusual or random experiences, because the healing is caused by structural changing of the brain, such as neurogenesis, which happened days to weeks after infusions.
Some experiences will be very pleasurable, relaxing, and meditative, while others will be challenging; the ketamine experience may bring out subconscious issues such as memories or trauma that can be overwhelming.
A challenging trip (rather than the term “bad trip”) can be very therapeutic and potentially even more can be gained and used from these experiences.
Different forms of ketamine
Intravenous (IV) and intramuscular (IM)
- IV is the superior route of administration- 100% bioavailability, can titrate and stop infusion, ability to treat side effects quickly with IV access (nausea, hypertension, tachycardia)
- IV ketamine has predictable and consistent effects and allows for ease of adjusting dose
- These forms are the most commonly studied and supported form of ketamine in the scientific community
Oral
- Some studies reported 4 to 6 weeks to see any antidepressant effect with oral ketamine, which is similar to traditional antidepressant medications
- Require higher doses and more potential for side effects given its lower bioavailability of approximately 20%
Nasal
- Only 40% bioavailable and less predictable experience (i.e., dose is dependent on rate of absorption and other patient-specific factors)
- No ability to stop or take back dose, rather patient must wait for effects to “run its course” and wear off
- Not monitored, potential for abuse, potentially less therapeutic
Types of responders and poor responders to ketamine
Early
Improve after 1 or 2 treatments then plateau
Standard
Incremental improvements within 3 or 4 treatments
Late
May require 5+ treatments before notice any benefits
Non-responders
1 in 5 or 15-20% of people; alternative non-ketamine treatments for non-responders CBT, ECT, EMDR, and TMS
Poor responders
- Elderly? Two randomized controlled trials: one showed that 69% response rate, the other showed decreased depression (MADRS) scores, but not statically significant (potential limitation of the study was the use of only nasal form of ketamine)
- Benzodiazepines and lamotrigine may reduce the effectiveness of ketamine when given the day of infusions
Ketamine safety
- No severe side effects or adverse reactions other than nausea at high dose and with head movement and visual stimulation
- Psychedelic naïve patients may experience anxiety given the normal emotional response from the medicine; this typically does not require pharmacological treatment, but rather reassurance and sometimes physical touch (e.g., hand holding)
- Normal response to have slight elevation of heart rate and blood pressure
- Non-addictive
- Recreational abuse of ketamine may cause bladder injury known as interstitial cystitis which is associated with daily high dosages (1+ grams); this can lead to a stiff bladder with decreased volume capacity and may require surgical intervention
The Innerbloom Ketamine Therapy approach to ketamine therapy
- Ketamine alone is not enough to cure depression, etc.
- Ketamine is a tool/catalyst rather than a magic pill that will solve all problems
- Ketamine is used to break negative thought patterns, behaviors, or destructive life cycles
- Do not plan to use ketamine for long-term, but rather temporarily until individuals are able to get back on the right path and make healthy lifestyle changes
- Preparation and integration and therapy is key
- The ideal scenario is to have therapy prior to ketamine infusion to start the preparation phase, then the day or days following an infusion to have therapy again during the “neuroplasticity window” or when brain is receptive and malleable to change which is termed the integration phase
The ketamine infusion process
- Multiple infusions (6+) over a short period of time 2–6 weeks
- Boosters available for patients who have already undergone a 6-infusion series
- Discourage single infusions: 4–5 infusions are felt to be necessary and fair trial to assess response to ketamine or determine if patients are non-responders
- Sitter: Someone is always with patient during infusions
What to expect after infusion
- Patients will need a ride home, are encouraged to have a light day after, and should expect to be back to normal in about 3 hours (half-life of ketamine is 3 hours), but they cannot drive for 12 hours after infusion
Preparation
- Preparation prior to infusions appears to be beneficial for achieving the proper mindset that allows for a therapeutic response; the goal of preparation is to maximize benefits and avoid potential risks or side effects
- Preparation may include education, attention to set and setting, and making use of strong support systems
Integration
- Integration refers to what is done after infusions or in between treatment sessions; this includes plans of action and changes in lifestyle in positive ways to achieve long lasting results after ketamine therapy
- Ketamine therapy alone will have beneficial effects, although integration enhances the therapeutic potential of the medicine
- Includes self-reflection, developing new routines and healthy daily habits along with help from a professional such as a therapist which may ultimately lead to long term positive changes
