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Ketamine for Depression

Although occasional feelings of sadness are a normal part of the human experience, clinical depression is characterized by prolonged states of sadness.  It is a chronic mental and behavioral health disorder that impacts numerous individuals worldwide.  Individuals with depression find themselves in significant distress and impairment of their daily lives.  Treating depression is already a uphill battle, and among those who receive treatment, approximately one-third of patients do not experience satisfactory responses to antidepressants and/or therapy. 

Study after study supports Ketamine as a safe and effective drug to treat depression.  Ketamine is particularly effective for patients with treatment-resistant depression (TRD),  or depression that does not respond well to many first-line treatments such as antidepressants or therapy.  AVYIA treats depression and other mood disorders in patient-centered fashion.  This starts by assessing patients for individual suitability and then developing a treatment plan based on a patient’s unique background.

Ketamine for Depression
Ketamine for Depression

AVYIA’s Ketamine Program is Also Designed to Treat Major Depression, Suicidal Thoughts, and More.

Research has demonstrated that ketamine can lead to rapid and substantial alleviation of depressive symptoms even in individuals with major depressive disorder.  Studies have shown that noticeable improvements in depression symptoms can be achieved within a matter of hours to days after starting ketamine treatment.  Our science-backed, evidence-based treatment programs can be a powerful solution for patients trying to feel better quickly, sustain disease remission, and be safe while doing so. 

Depression is closely associated with suicidal ideation (SI), or suicidal thoughts.  SI requires immediate attention, and for many, ketamine is able to rapidly reduce or resolve suicidal thoughts.  AVYIA clinicians will prioritize patients suffering from suicidal thoughts, so please don’t hesitate to get help if you or a loved one is suffering.  Individuals suffering from SI should have a suicide prevention protocol with their primary or mental health provider.  Patients should always call 911, 988, or seek emergency help should their suicidal thoughts escalate in intensity, frequency, or turn into an active plan to hurt themselves or others.  

Key Statistics for Depression in the US

Prevalence

National Institute of Health (NIH) in 2020 estimates 21 million individuals in the US suffered from a depressive episode and 14.8 million individuals had major depression with severe impairment and detriment to the quality of life.

Age of onset

Age of onset

Depression can occur at any age, but the median age of onset is around 32 years old. American adults with a major depressive episode is highest among individuals aged 18-25 (17.0%), then follow by 26-49 (9.1%) and 50+(5.4%).

Gender differences

Women are more likely to experience depression than men. In fact, women are almost twice as likely as men to experience major depressive episodes.

Comorbidity

Depression often occurs alongside other mental health disorders, such as anxiety, PTSD, bipolar, and eating disorders.

Disability

Depression can be a disabling condition, with up to 50% of individuals with depression experiencing significant impairment in their daily lives. However, only 2 out of 3 individuals received care for their depression

Access to treatment

Unfortunately, many individuals with depression do not receive adequate treatment. One study found that only about one-third of individuals with depression receive appropriate treatment.

What Are The Different Types of Depression?

Clinical depression is a medical condition that may cause serious, long-lasting symptoms and often disrupts a person’s ability to perform routine tasks. Below are different types of depression commonly diagnosed:

Major Depressive Disorder (MDD) – it is known as clinical depression, which involves persistent feelings of sadness, loss of interest or pleasure, and other symptoms that significantly impact daily functioning. MDD is the most common form of depression.

Persistent Depressive Disorder (PDD) – Formerly known as dysthymia, PDD involves a chronic and long-lasting depressed mood that persists for at least two years. People with PDD may experience periods of major depressive episodes along with milder symptoms.

Bipolar Depression – This disorder involves alternating periods of depression and mania or hypomania. During the depressive phase, individuals experience symptoms like major depressive disorder and other times exhibits high level of anxiety. It’s important to note that patients actively in mania or hypomania, should not receive ketamine at that time.  Read more here (bipolar link)

Seasonal Affective Disorder (SAD) – SAD is a type of depression that occurs in a seasonal pattern, typically during the winter months when there is less sunlight. Symptoms include low energy, oversleeping, weight gain, and a general feeling of sadness.

Postpartum Depression (PPD) – PPD occurs in women after giving birth and is characterized by intense feelings of sadness, anxiety, and exhaustion. It can affect the ability to care for oneself and the newborn.

Atypical Depression – This type of depression involves a unique set of symptoms, including oversleeping, increased appetite, weight gain, mood reactivity (being able to experience temporary improvements in response to positive events), and extreme sensitivity to rejection.

Psychotic Depression – In addition to depressive symptoms, psychotic depression involves hallucinations, delusions, or other forms of psychosis. Individuals may experience false beliefs or hear voices that are not present.  Note that ketamine may not be the right treatment for this disorder.

How-does-IV-ketamine-treat-depression_

Using an eye mask helps to block out external visual stimuli, which allows patients to focus inward and have a more immersive experience. It also enhances relaxation and provides a sense of privacy when experiencing their ketamine treatments.  

How Does Ketamine Treat Depression?

Ketamine alleviates depression by blocking the NMDA receptor (N-methyl-D-aspartate) and regulates the neurotransmitters glutamate and AMPA.  This receptor plays a crucial role in regulating the capability of synapses, helping its ability to escalate or diminish movement of neurotransmitters, and improving synaptic plasticity (neuroplasticity). The NMDA receptor is closely associated with excitotoxicity, a process connected with depression, where nerve cells are either impaired or perished because of excessive stimulation.  By blocking the NMDA receptor to regulate the neurotransmitter glutamate and preventing synapses from over-exciting, ketamine can aid in treating depression in a rapid and sustained way.

Ketamine has been found to enhance neuroplasticity by boosting the production of brain-derived neurotrophic factor (BDNF), a crucial protein that supports the brain’s adaptive capabilities.  Neuroplasticity is further enhance when ketamine works on the mTOR pathway and inhibits eEF2 kinase.  Many experts theorize that the psychedelic and dissociative properties of ketamine may also play a role in promoting neuroplasticity.  Neuroplasticity is the brain’s capacity to adjust and transform itself in light of novel experiences.  The stimulation of neuroplasticity through ketamine could potentially lead to rewiring of the brain and the development of fresh neural connections, leading to relief from depressive symptoms and many other mental health disorders.    

At low dosages, ketamine’s safety profile makes it an attractive option as a fast-acting antidepressant.  According to scientific research, the benefits of IV ketamine therapy are felt even after a single session.  Ketamine is listed in the World Health Organization’s List of Essential Medicines, which includes most effective and safe medicines for a modern health system.  Simply put, ketamine is one of the most important medicines in the world for efficacious, safe and cost-effective treatments. 

Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry. 2019 Sep-Oct;61(5):480-485. doi: 10.4103/psychiatry.IndianJPsychiatry_484_18. PMID: 31579184; PMCID: PMC6767816.

What Happens During Ketamine Treatment?

IV or Nasal Ketamine Treatment

Ketamine therapy administered via intravenous infusion lasts around 40 minutes and is dosed lower than what’s used in anesthesia cases.  AVYIA’s IV program consists of 6 treatment sessions over 3 weeks.  Alternatively, nasal inhalation treatments consists of 8 treatments over 4 weeks.   These evidenced-based programs are designed to help patients reach optimal results, while being mindful of costs.  Additional single booster sessions may be required from time to time should the patient relapse from their symptoms.  

During each treatment session, patients are encouraged to lay comfortably, listen to smoothing music and have eye shades on.  This environment is ideal due to ketamine’s psychedelic and dissociative effects, or out-of-body experience.  These effects are short-lived, and disappear shortly after the treatment is completed.  Each appointment lasts approximately 2 hours, which includes assessment, treatment, and monitoring time.  

Microdosing Treatment

An alternative option to IV or intranasal ketamine is daily microdosing in oral sublingual form (under the tongue).  As the name suggests, patients in this program take a smaller dose of ketamine than they would receive in IV or nasal form, but therapeutic effects are achieved by taking ketamine on a daily basis.  This is a great option if patients do not wish to undergo the dissociative effects associated with IV and nasal ketamine.    

AVYIA’s providers will guide you through the entire process, as well as teach you how to titrate and manage your daily doses.  Typically, your ketamine will be taken once at night, but may vary from patient to patient based on individual needs and medical backgrounds.  Side effects are generally rare, minimal, or well tolerated.  AVYIA monitors and follows patients closely for safety and progress assessments.  

What Does Ketamine Feel Like?

Therapeutic IV or Intranasal Treatment

Patients should expect relatively rapid symptom relief when starting ketamine.  For some, relief comes in minutes or hours, but for others, relief may come after a few treatment sessions.  Psychedelic or dissociative effects may occur during IV or intranasal ketamine therapy.  Patients often describe feeling as if they are floating outside their bodies, leaving their physical selves behind, and experience heightened sensory awareness.  Visual and auditory perceptions may be enhanced.  Colors may seem brighter and sounds to be more clear.  Commonly referred to as “a trip,” this is also called the dissociative effect or psychedelic effect, and does not last long after the ketamine treatment is completed.  Some patients are mildly anxious or emotional during their experiences, while others enjoy the experience or find it enlightening.  Everyone, and every experience is different.     

Occasionally, a patient may come out of the treatment with a false epiphany, such as knowing the meaning of life, or other grand ideas.  This is also short-lived, as these ideas disappear in a day or two.  We recommend against making rash decisions off of these ideas.  

Microdosing Treatment

The intensity of the drug’s effect is typically lower in oral microdosing compared to IV or intranasal ketamine.  However, patients microdosing ketamine should expect noticeable relief of symptoms within the first few days to a week of starting the drug.  Some may experience a gradual improvement, and others a sudden change in improved mood.  We commonly see patients noticing their symptoms “just lifted all of a sudden.”  Sustaining symptom relief is obviously the initial goal, but complete remission is what is ultimately desired.   

Ketamine in microdose form requires an easy-to-follow titration of the drug with the guidance of AVYIA’s clinicians.  This is to help prevent dosing to the point of dissociation.  The goal of microdosing ketamine is to avoid the dissociative effects so that patients may continue daily life without impairment.  

 

What Happens After Your Ketamine Treatment?

Individual Variation in Response

Sustaining Treatment Response

IV and nasal ketamine can provide rapid relief from depressive symptoms. How long the therapeutic effects lasts vary from person to person. For some individuals, disease remission is achieved after completion of a treatment program. For others, the initial benefits may be temporary, and symptoms may start to resurface over time. Booster IV or nasal sessions will help to sustain and extend the treatment response, providing ongoing relief from depressive (or anxiety) symptoms.

Individual Variation in Response

We cannot predict the duration of sustaining remission or how quickly remission is achieved with ketamine. Most patients achieve remission after completion of an IV or intranasal ketamine program. On average, microdosing patients achieve remission in 8-9 months. AVYIA works with all patients every step of the way in a personalized and patient-centered approach in order to achieve remission of their disorders.

Maintenance of Remission

Ketamine therapy has been found to induce remission in some individuals, where they experience a significant reduction or complete absence of symptoms for years. For other, maintaining remission requires a periodic booster session or transitioning to microdosing. The goal is to eventually not require ketamine, or any medication, to be in a health state of mind.

Treatment Optimization

Frequent follow-ups are included in each of AVYIA's treatment programs, as it leads to optimized outcomes and patient satisfaction. This means patients will receive post treatment assessments after completing a course of IV or nasal ketamine. Microdosing patients will be in constant contact with clinicians to titrate doses and monitor progress.

Kryst, J., Kawalec, P., Mitoraj, A.M. et al. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol. Rep 72, 543–562 (2020). https://doi.org/10.1007/s43440-020-00097-z

Why Should I Use Ketamine for Depression?

Ketamine therapy in IV and intranasal form starts working after the first session. Each additional session sees compounding rapid improvements in the patient's symptoms. After the treatment program, many patients will experience complete resolution or remission of their symptoms, while others will need occasional ketamine infusion boosters to stay in remission.

Studies have found that ketamine therapy can offer immediate relief and sustained relief of depressive symptoms in individuals with treatment-resistant depression. In a 2017 study, 64% of treatment-resistant participants had at least a 50% reduction in depressive symptoms after just one treatment session!

Conventional treatments, like antidepressant medications, counseling, and psychotherapy alone, may take weeks to months for a patient to start feeling better.

Current pharmaceutical drugs have a poor side effect profile. Many patients experience long-lasting unpleasant side effects from their depression medications. Sexual dysfunction, weight gain, and apathy are common side effects of those types of drugs.

About a quarter of patients do not respond to a new mental health drug, and may even start feeling worse! The trial-and-error process of finding the correct antidepressant is oftentimes frustrating because it may take months to years to find the correct regimen.

A recent study has shown approximately 30% of patients treated for major depression have treatment resistance to conventional treatment modalities. Conventional treatments include counseling, psychotherapy, and medications (antidepressants, SSRI, SNRI, MAOI, DRI, antipsychotics, and mood stabilizers).

Kverno KS, Mangano E. Treatment-Resistant Depression: Approaches to Treatment. J Psychosoc Nurs Ment Health Serv. 2021 Sep;59(9):7-11. doi: 10.3928/02793695-20210816-01. Epub 2021 Sep 1. PMID: 34459676.

Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA Jr, Sanacora G. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018 Feb 1;175(2):150-158. doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3. PMID: 28969441; PMCID: PMC5794524.

What is Dysthymia and What are The Symptoms?

Dysthymia, also known as persistent depressive disorder (PDD) is a chronic form of depression that lasts for two years or more. Symptoms are not as severe as major depression but can interfere with daily functioning and quality of life. The symptoms of this condition usually include:

Depressed Mood: This is the primary symptom. Adults might feel sad or “down in the dumps”. For children and adolescents, depression can manifest as being irritable.

Loss of Interest: People with PDD may lose interest in daily activities or hobbies that they once enjoyed.

Change in Appetite: This can either be an increased appetite leading to weight gain or a decreased appetite leading to weight loss.

Sleep Disturbances: Some individuals may experience insomnia, while others might oversleep.

Low Energy or Fatigue: Feeling tired almost every day is a common symptom

Low Self-esteem: Individuals with PDD frequently have a poor self-image.

Poor Concentration or Difficulty Making Decisions: Everyday tasks can become challenging due to an inability to focus or make decisions.

Feelings of Hopelessness: A pervasive feeling that things won’t get better can dominate the individual’s outlook.



Depression Treatments Available at AVYIA

At AVYIA, we understand that depression can manifest in various forms, affecting individuals in unique ways.  We offer a safe and effective solution to help you overcome all types of depression.  Our ketamine therapy treatment is designed to address various forms of depression, including:

  • Treatment-Resistant Depression (TRD)
  • Major Depressive Disorder (MDD)
  • Bipolar Disorder
  • Persistent Depressive Disorder (PDD or Dysthymia) 
  • Postpartum Depression (PPD)
  • Post-Traumatic Stress Disorder or PTSD 
  • Suicidal Ideation 
* Microdosing costs $150 per month for most patients. For patients who require higher dosages, the cost may increase due to the higher cost of the medication. Microdosing patients are required to have an at-home visit before commencing the medication.

FAQ

AVYIA offers ketamine in 3 routes of administration (programs) – intravenous, intranasal and oral microdose.

Intravenous (IV):  6 treatment sessions over 3 weeks.  This is the most studied administration route, and generally preferred by clinicians.  IV infusion affords a 100% bioavailability rate and the dosage can be titrated precisely. This allows the drug to reach therapeutic effects quicker and sustain it more uniformly during the treatment session.

Intranasal:  An easy to use nasal spray that is guided by a clinician at bedside.  This is for patients who have a fear of needles and IVs.  Nasal sprays have a slightly lower bioavailability or absorption, however, therapeutic effects can be achieved in a less invasive fashion. 

Oral Microdosing:  Ketamine is taken with a liquid solution or tablet under the tongue (sublingual) so that ketamine can be absorbed better into the bloodstream and bypass the digestive system.  This is a lower dosage regimen, which is designed to achieve therapeutic effect without triggering the dissociative effect seen in IV or nasal spray.

Results vary from patient to patient and study to study, but most of the data results are from studies using IV administration.  If we were to combine the most recent body of science papers studying ketamine infusions, approximately 60-80% of patients reported improvement in their moods after multiple treatments.  A 2020 review of the science by Wilkowska, et al, reported a 63.2-73.7% remission rate after 6 low-dose ketamine treatments.  Single treatment sessions were less favorable compared to multiple treatments. 

At AVYIA, we recommend combining ketamine infusions with ketamine-assisted psychotherapy, which consists of individualized counseling or therapy sessions to improve patient outcomes.

Sustainment of being depression-free after completion of a program varies from weeks to months to years (complete remission).  We cannot predict patient’s outcomes unfortunately.  Single boosters treatments may be required if symptoms relapse.  

No.  We ask patients to fast 6-8 hours prior to each IV or intranasal treatment.  

Microdose patients may resume normal daily life without any dietary restrictions.  

With IV and Intranasal ketamine treatments, patients can expect possible mild hallucinations (psychedelic effect) and dissociative effects (out-of-body experience).  It is also common for patients to feel drowsy after a treatment.  After completion of a treatment, some patients have reported false epiphanies, such as “knowing the meaning of life.”  We recommend against making rash decisions after each treatment session.  These effects disappear shortly after the treatment is completed.

Driving and potentially dangerous activities should be avoided until the impairment has subsided.  Our health care provider will monitor you after your treatment is completed.  We ask that a responsible adult also accompany you during and after your treatment.  

With AVYIA’s microdosing regime, dissociative effects are avoided by taking a lower dose, spread out as a daily tablet. 

Ketamine is a safe drug, especially while under the supervision of a trained clinician.  Most tolerate ketamine quite well.  Some will experience drowsiness or nausea.  Nausea is easily relieved during an IV or intranasal treatment session with the use of antiemetics or anti-nausea medications.  Nausea from microdose ketamine is resolved by dosage or timing adjustments.  

Transient hypertension, or brief elevations of blood pressure is another potential side effect when given in IV or intranasal form.  Blood pressures normalize immediately after ketamine is completed.  Patients with a history of hypertension will be screened and monitored closely.  Uncontrolled hypertension is generally contraindicated until blood pressure is stabilized.  

Psychedelic or dissociative effects are typically seen in IV or intranasal administration, but effects are short-lasting.  

AVYIA recommends 6 Ketamine IV infusions over a 3 week period for optimal results.  Intranasal Ketamine is an acceptable alternative that uses 8 treatments over 4 weeks. Some patients go into complete disease remission after completing a treatment program, meaning they are essentially “cured.”  Others see their symptoms relapse after a period of time.  We cannot predict if and when depression symptoms come back.  

Following the completion of an initial treatment program, patients may commence in a maintenance program should their symptoms relapse, wherein they are eligible to receive discounted single booster treatments as needed until remission is achieved.  

Healthy teens and adults typically can tolerate ketamine safely, with minimal to no side effects.  AVYIA’s clinicians follow-up with patients regularly and closely as an additional safety measure.

Patients with a history of hypertension or high blood pressures, should continue taking their medications as directed and see that their pressures be in good control, which is generally under 140/100.  Uncontrolled blood pressure readings will require medications adjustments or lifestyle changes until acceptable pressures are reached.  Close blood pressure monitoring takes place during each IV or intranasal ketamine treatment, and on occasion, an extra dose of blood pressure medication may be required to safely lower a patient’s blood pressure. 

Patients recently or currently in a state of psychosis, mania, or hypomania, should not undergo ketamine therapy, as it may worsen their symptoms.  Once patients are stable or at their baseline mental health, please contact us to schedule a medical assessment for ketamine therapy eligibility.  We will be happy with work with you, your loved ones, and your mental health provider in this difficult time.  

Generally, ketamine is contraindicated in patients with a history of schizophrenia, schizo-affective disorder, interstitial cystitis, uncontrolled hypertention, certain severe heart diseases, and increased intracranial pressure or intracranial bleeding.  

Feel free to call us if you’d like to discuss your history and eligibility to receive ketamine.  

For more frequently asked questions, please visit our FAQ page.