Imagine a treatment for depression that works within hours rather than weeks, providing relief for those who have tried countless medications without success. Ketamine-assisted psychotherapy for depression is rapidly gaining attention as an important option for individuals battling treatment-resistance. With its unique mechanism of action and rapid onset of effects, ketamine offers hope for those seeking an alternative to traditional antidepressants. In this article, we’ll delve into the science behind ketamine therapy, explore its benefits, and guide you through the treatment process to help you understand how it could transform your mental health journey.
What is Ketamine and How Does It Work?
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used as an anesthetic for decades. In recent years, its potential as a rapid-acting antidepressant has gained significant attention in the field of psychiatry. When used at subanesthetic doses, ketamine can produce rapid antidepressant effects.
Ketamine-Assisted Psychotherapy vs Traditional Antidepressants
Ketamine-assisted psychotherapy represents a significant shift from traditional antidepressant treatments. As someone who’s been working in this field for a long time, I can tell you that ketamine’s unique mechanism of action sets it apart from conventional medications, offering hope for those who’ve struggled with treatment-resistant depression.
Rapid onset of action
One of the most striking differences between ketamine and traditional antidepressants is the speed at which it works. While conventional medications often take weeks to show effects, ketamine can provide relief within hours or days. This rapid antidepressant effect is particularly crucial for individuals experiencing severe depressive symptoms or suicidal ideation.
In my experience, this quick onset can be life-changing for patients who’ve been waiting weeks or months for traditional antidepressants to kick in.
Mechanism of action
Ketamine’s effectiveness stems from its unique interaction with the brain. Unlike traditional antidepressants that primarily target serotonin, norepinephrine, or dopamine, ketamine works as an N-methyl-D-aspartate (NMDA) receptor antagonist. This mechanism leads to increased glutamate transmission and promotes synaptic plasticity.
What does this mean for you? Essentially, ketamine can help rewire neural pathways, also potentially reversing the damage done by chronic stress and depression. This neuroplasticity-enhancing effect is why many researchers believe ketamine could offer longer-lasting benefits compared to traditional antidepressants particularly when combined with psychotherapy to ingrain new habits of thinking and behaving.
Treatment approach
Ketamine-assisted psychotherapy combines the biological effects of ketamine with targeted psychotherapy sessions. This integrated approach aims to leverage the increased neuroplasticity induced by ketamine to facilitate deeper therapeutic insights and lasting behavioural changes.
Neurological evidence on ketamine’s brain effects show a reduction in activity in the default mode network of the brain. This brain network is the network active when we are at rest and is thought to be involved in mental health conditions. The fixed patterns of thinking and behaving, like rumination and negative thought patterns, are thought to be a part of the default mode network. Ketamine temporarily reduces activity in the default mode network, and improves neuroplasticity. The combination with psychotherapy allows ketamine to be a potent catalyst for psychological and behavioural change for patients with mental health conditions broadly and depression specifically.
In contrast, traditional antidepressant treatments, while they may be combined with therapy, may not enhance the therapeutic process in the way ketamine does. This synergistic effect of ketamine and psychotherapy could lead to more comprehensive and enduring improvements in mental health.
Types of Depression That May Benefit From Ketamine-Assisted Psychotherapy
Ketamine-assisted psychotherapy has shown remarkable potential in treating various forms of depression.
Treatment-resistant depression
Treatment-resistant depression is perhaps the most well-known candidate for ketamine therapy. The research base for low dose ketamine in mental health is the most substantial for treatment resistant depression. In my own practice, I’ve seen patients who’ve tried multiple antidepressants without success find relief with ketamine. For treatment resistant depression, or those who haven’t responded to two or more traditional antidepressants or psychotherapy, ketamine therapy offers a new avenue for treatment when other options have been exhausted.
Major depressive disorder
For individuals with major depressive disorder, sometimes referred to by clinicians as “unipolar depression”, ketamine-assisted psychotherapy can be a life changing treatment option. It’s not just about managing symptoms; it’s about potentially rewiring the brain’s response to stress and negative thought patterns. The N-methyl-D-aspartate (NMDA) receptor antagonist properties of ketamine contribute to its unique mechanism of action.
I’ve observed patients with severe depression experience significant improvements in their mood, energy levels, and overall quality of life after ketamine treatments. The combination of ketamine’s neuroplasticity-enhancing effects, default mode dampening effects and targeted psychotherapy can lead to more comprehensive and lasting improvements.
Bipolar depression
Ketamine has also shown promise in treating the depressive episodes of bipolar disorder. This is particularly significant because bipolar depression can be notoriously difficult to treat with conventional antidepressants, particularly in the subtype known as Bipolar type II. In some cases traditional antidepressants may trigger manic episodes. The “affective switch”, or the switch from depression to mania, is a risk which clinicians monitor for. Ketamine’s rapid action can provide quick relief from depressive symptoms.
The unique challenges of bipolar disorder necessitate a tailored approach to ketamine-assisted psychotherapy. While the risk of inducing mania is thought to be low and not seen in clinical trials of ketamine and bipolar depression, typically patients with bipolar depression are advised to remain on some form of anti manic therapy as a precaution before starting ketamine-assisted psychotherapy. It’s crucial to note that ketamine treatment for bipolar depression requires careful monitoring and should only be administered under the supervision of a qualified healthcare provider.
Postpartum depression
Postpartum depression is a form of depression that follows childbirth and the incidence is thought to be around 12% of pregnancies with significant impairments. Ketamine and esketamine, one of the two molecules that make up ketamine, have been shown to prevent and reduce incidence of post partum depression when given in the period of delivery or soon afterward. One publication reviewing randomized controlled trials cites esketamine with pregnant women undergoing caesarean section without the use of esketamine, those using esketamine in the perioperative period showed a 48% decreased risk of developing postpartum depression. These papers are citing studies with single treatments of ketamine or esketamine. Given literature on treating depression more broadly, a cumulative series and integrating psychotherapy like Field Trip’s Ketamine-Assisted Therapy approach may be even more beneficial for those struggling with or at risk for postpartum depression. Indeed, emerging evidence is showing rapid improvement in postpartum depression with ketamine plus psychotherapy with sustained benefit.
Ketamine Therapy for Depression – Eligibility
Before starting ketamine therapy, you’ll undergo a comprehensive evaluation by a prescribing mental health clinician. This assessment typically includes a review of a patient’s medical history, current medications, and previous treatments for depression. At Field Trip Health, we’ll also conduct a thorough psychiatric evaluation to determine if ketamine therapy is appropriate for their specific case.
Eligibility criteria often include a diagnosis of treatment-resistant depression, meaning you’ve tried multiple antidepressants or therapies without success. We’ll also assess for any contraindications, such as certain cardiovascular conditions, pregnancy or a history of a psychosis. It’s crucial to be open about your medical history to ensure your safety during treatment.
Ketamine Administration Methods
Once deemed eligible, we’ll discuss the various ketamine administration methods. The most common form is intravenous infusion, which offers the highest bioavailability. However, other options include intranasal sprays (like Spravato), intramuscular injections, and oral lozenges. The choice depends on factors like the patient’s medical history, preferences, and the specific protocols of the treatment facility.
For intravenous ketamine, patients receive a subanesthetic dose over about 40 minutes to an hour. The dosage is carefully calculated based on their body weight and individual response. Throughout the infusion or dosing session, we’ll monitor the patient’s vital signs and overall well-being. It’s normal to experience mild dissociative effects during treatment, but these typically subside shortly after the infusion ends.
Frequency and Duration of Ketamine-Assisted Psychotherapy
Ketamine-assisted psychotherapy for depression follows a structured protocol, balancing the need for rapid relief with long-term therapeutic benefits. The frequency and duration of treatments are tailored to each individual’s needs, depression severity, and response to the therapy.
Initial ketamine treatment phase
The initial phase of ketamine therapy usually consists of a series of treatments administered over a short period. Most protocols for depression involve 4 to 6 intravenous infusions or dosing sessions given over 2 to 3 weeks. This intensive approach aims to quickly alleviate depressive symptoms and jumpstart the healing process. Studies have converged on twice weekly for three weeks being the standard of care in ketamine for depression.
In my experience, during this phase, many patients report significant improvements in mood, anxiety symptoms, and overall well-being. The rapid antidepressant effect of ketamine can also be beneficial for those experiencing suicidal ideation or severe depression.
Maintenance treatment
After the initial treatment phase, many patients will benefit from maintenance treatments to sustain the antidepressant effects. The frequency of these maintenance sessions varies widely depending on individual needs and responses. Some patients may require monthly infusions or dosing sessions, while others might maintain improvements with treatments every few months.
While the data shows that maintenance in some form may prevent relapse, combining ketamine with psychotherapy may enhance the response and provide for longer-lasting changes. In addition, the psychological shifts and often processing of past trauma may reduce the need for maintenance. Ketamine acts as a catalyst for change, combined with psychotherapy and other therapeutic strategies to achieve lasting improvements in mental health. The decision for maintenance is based on a variety of patient specific factors like treatment response, duration of benefit, the underlying diagnosis, psychological shifts during treatment, and patient finances among others.
Integrating psychotherapy
Ketamine-assisted psychotherapy isn’t just about the infusions or the medicine on its own. We have seen that taking ketamine from sterile hospital settings to warm, therapeutic psychotherapy settings has a positive effect on the patient experience. To borrow from the paradigm of psychedelic assisted psychotherapy, the mindset (Set) and Setting of the patient can dramatically change the experience of the medicine for the patient, improving the potential for breakthroughs. Adding a psychotherapy component to ketamine has been shown in some trials to enhance the effects of ketamine in both effectiveness and duration of effects. Therapy sessions are often scheduled before, during, and after ketamine treatments to help patients process their experiences and integrate insights into their daily lives.
The frequency of these therapy sessions may be higher during the initial treatment phase and taper off as the patient stabilizes. However, ongoing therapeutic support is generally recommended to maintain progress and prevent relapse.
Effectiveness of Ketamine-Assisted Psychotherapy for Depression
Ketamine-assisted psychotherapy has shown significant effectiveness in treating depression, particularly for those who haven’t responded well to traditional treatments.
Rapid and sustained relief
One of the most striking aspects of ketamine therapy is its rapid antidepressant effect. Unlike conventional antidepressants that can take weeks to show results, ketamine often provides relief within hours or days. This quick onset can be life-changing, especially for those grappling with severe depression or suicidal ideation.
Moreover, the combination of ketamine with psychotherapy may allow for the sustaining of antidepressant response for many patients. Many patients experience sustained improvement in their depression symptoms even after the initial treatment phase. This durability is partly due to ketamine’s unique ability to promote neuroplasticity, essentially helping the brain form new, healthier neural connections, combined with psychotherapy to make those patterns of thinking and behaving more enduring.
Efficacy in treatment-resistant depression
Ketamine-assisted psychotherapy has shown particular promise in treating treatment-resistant depression. A significant number of patients who haven’t responded to multiple traditional antidepressants find relief with ketamine. This effectiveness is backed by numerous clinical trials and real-world evidence.
Recent studies have further solidified ketamine’s efficacy in treatment-resistant depression. For instance, a study found that the mean change in Montgomery–Åsberg Depression Rating Scale (MADRS) score at day 15 was -18.4 for ketamine compared to -5.7 for placebo. This substantial difference highlights ketamine’s rapid-acting properties and its potential to provide swift relief for those struggling with severe depressive symptoms.
Moreover, ketamine has demonstrated effectiveness in bipolar depression, a condition that can be difficult to treat with conventional methods. Adding to the substantial body of evidence, a 2023 study showed ketamine’s non-inferiority to electroconvulsive therapy (ECT) for treatment-resistant depression, without the cognitive side effects often associated with ECT. This finding is particularly significant, as it offers a potentially safer alternative for patients who might otherwise consider ECT as a last resort.
Combining biological and psychological approaches
The effectiveness of ketamine-assisted psychotherapy lies in its dual approach. The ketamine infusions or doses work on a biological level, rapidly altering brain chemistry and neural networks to alleviate depressive symptoms. Meanwhile, the psychotherapy component helps patients process their experiences and integrate insights gained during ketamine sessions into their daily lives.
This combination of pharmacological intervention and targeted psychotherapy creates a synergistic effect. It not only addresses the immediate symptoms of depression but also helps patients develop long-term coping strategies and resilience. As a result, many find that ketamine-assisted psychotherapy offers a more comprehensive and enduring solution to their depression than medication alone.
How to Find Qualified Ketamine Therapy Provider
When seeking ketamine therapy, it’s essential to find a prescribing clinician or clinic with experience in this specific treatment. Look for medical professionals who specialize in treatment-resistant depression and have a track record of administering ketamine therapy. Don’t hesitate to ask about their qualifications, experience, and success rates with ketamine treatments.
I recommend researching clinics that offer comprehensive care, combining ketamine dosing sessions with psychotherapy sessions. We take this integrated approach at Field Trip Health, as it yields significantly better treatment outcomes than ketamine alone. Remember, ketamine therapy is most effective when administered by healthcare providers who understand its unique mechanism of action and can tailor the treatment to your specific needs, along with trained therapists like those at Field Trip Health that can use the ketamine experience to maximize mental health breakthroughs and transformation.
Ketamine Therapy Insurance Coverage and Costs
The cost of ketamine-assisted psychotherapy can vary widely depending on your location and the specific treatment protocol. While ketamine therapy is becoming more widely accepted, and insurance coverage can vary, insurance plans have expanded mental health coverage over the years. Some private insurance plans may cover all or portions of the treatment, especially when combined with psychotherapy sessions.
Many clinics offer package deals for a series of ketamine infusions or dosing sessions, which can help reduce overall costs. It’s worth discussing payment options including payment plans that can improve affordability. Remember, while the upfront cost may seem high, ketamine therapy’s rapid antidepressant effect and potential for long-lasting relief can make it a cost-effective option in the long run, especially for those with treatment-resistant depression.
Health Canada Approved Options: Esketamine (Spravato)
In Canada, while ketamine’s use for depression treatment is considered “off-label,” there is a Health Canada approved option: Esketamine, marketed as Spravato. Spravato is a nasal spray form of ketamine that’s been specifically approved for treatment-resistant depression. It’s administered under medical supervision in offices of physicians or prescribers certified by Janssen, the parent company behind Spravato.
However, it’s important to note that many clinicians, myself included, still prefer generic racemic ketamine over Spravato. Racemic ketamine, offers higher bioavailability, has a longer track record of use in depression treatment, is generally more cost effective and may be even more effective than Spravato according to some published evidence.
Combining Ketamine Therapy with Lifestyle Changes
Incorporating lifestyle changes can significantly enhance the efficacy of ketamine therapy. Regular exercise, for instance, has been shown to boost mood and increase neuroplasticity, complementing ketamine’s effects on the brain. I often recommend patients engage in physical activities they enjoy, whether it’s yoga, walking, or more intense workouts.
Nutrition also plays a vital role. A balanced diet rich in omega-3 fatty acids, vitamins, and minerals can support overall brain health. Additionally, improving sleep can enhance mood regulation and cognitive function, further supporting the therapeutic process. Socialization and sun exposure also have benefits for patients with depression.
Regardless of the primary therapeutic modality used, I advocate lifestyle interventions to all of my patients with depression, including exercise, socialization, behavioural activation (deliberately practicing certain behaviours), good nutrition and healthy sun exposure.
What to Expect During and After Ketamine-Assisted Psychotherapy
Ketamine-assisted psychotherapy is a unique experience that combines the biological effects of ketamine with targeted psychological interventions. I’ve guided many patients through this process so let me provide some insights into what you might expect during and after ketamine-assisted psychotherapy.
During ketamine-assisted psychotherapy
During a ketamine infusion or dosing session, you’ll be in a comfortable, controlled environment. The treatment typically lasts about an hour. You might experience mild dissociative effects, such as feeling detached from your body or surroundings. Some of my patients report visual or auditory changes, but these are temporary and subside soon after the session ends.
Throughout the session, a healthcare provider will monitor your vital signs and overall well-being. It’s important to remember that while the experience can be intense, it’s also brief and carefully managed. Many patients find these sessions to be profoundly introspective and even transformative.
Immediate post-treatment effects
Immediately after the infusion or dosing session, you might feel groggy or slightly disoriented. This is normal and usually clears within an hour or two. Some patients report feeling emotionally raw or vulnerable, while others experience a sense of calm or clarity. It’s crucial to have someone drive you home after the treatment, as you shouldn’t operate a vehicle for at least 24 hours post-infusion or session.
In terms of mood effects, many patients report rapid improvements in depressive symptoms, often within hours or days of the first treatment. This quick onset of action is one of the most striking aspects of ketamine therapy, especially for those accustomed to the weeks-long wait associated with traditional antidepressants.
Long-term effects of ketamine-assisted psychotherapy
The long-term effects of ketamine-assisted psychotherapy can be profound. Many of our patients experience sustained improvements in mood, anxiety symptoms, and overall quality of life. However, it’s important to note that ketamine isn’t a “magic bullet.” The most successful outcomes typically involve integrating the insights gained during treatment into daily life through ongoing psychotherapy and lifestyle changes.
In the weeks and months following treatment, you’ll likely continue with regular therapy sessions to process your experiences and build on the progress made. This integration phase is crucial for translating the neuroplasticity-enhancing effects of ketamine into lasting behavioural and cognitive changes.
Ketamine-Assisted Psychotherapy at Field Trip Health
At Field Trip Health, we offer an immersive in-person Ketamine Assisted Therapy program designed to help you achieve deep breakthroughs and address the root causes of your mental health challenges. Our approach combines the Health Canada and FDA-approved medicine ketamine in low doses for depression with personalized psychotherapy to promote lasting healing and transformation.
At Field Trip Health, we prioritize creating a safe, comfortable environment for your ketamine therapy sessions. Our team of experienced healthcare professionals closely monitors your progress throughout the treatment process, ensuring your safety and optimizing your therapeutic outcomes.
We’ve established a network of ketamine therapy clinics across Canada to make ketamine-assisted treatments more accessible. You can find our clinics in major cities including Toronto, Vancouver, Montreal, Ottawa, Hamilton, and Kitchener Waterloo, as well as in Thunder Bay and Sault Ste. Marie.
Each of our clinics maintains the high standards of care that Field Trip Health is known for, ensuring you receive consistent, quality treatment regardless of which location you choose. Our goal is to make ketamine-assisted psychotherapy available to those who need it most, providing a new path forward in mental health care.
About the Author
Dr. Mario Nucci MD CCFP is a licensed Family Physician with a passion for mental health and the development of new therapies. He is actively engaged in research with a faculty associate professorship at Northern Ontario School of Medicine, and research collaborations with the University of Ottawa, University of Calgary, Lakehead University, Concordia University and Vancouver Island University.
Dr. Nucci is the founder of Bay and Algoma Health Centre in 2019, a walk-in and addiction medicine clinic. He founded the Canadian Centre for Psychedelic Healing in 2019, now operating as Field Trip Health, providing cutting edge mental health care in Toronto, Montreal, Vancouver, Ottawa, Hamilton, Kitchener-Waterloo, Thunder Bay, Sault Ste. Marie, and at-home.
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