Ketamine Questions & Answers

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What does "off-label" ketamine use mean?

What is the success rate of ketamine for depression?

How quickly will the ketamine work on my depression?

What should I do throughout the week while I am receiving ketamine?

How should I expect to feel after my ketamine infusion?

Do I need to stop my other medications?

When should I stop eating and drinking before my infusion?

What will the “dissociation” I feel with ketamine be like?

What should I eat or drink afterwards to help with my recovery?

What if I feel nauseous post-infusion?

What should I do if I feel constipated?

When can I drive?

Is ketamine safe?

What are the side effects of ketamine?

Is ketamine addictive?

Can I develop a tolerance to ketamine?

Key Points:

Ketamine works through changes in the neurotransmitter Glutamate.
Ketamine has both short-term and long-term impact on the brain.
Ketamine is an effective treatment for Resistant Depression.

What is Major Depressive Disorder?

Major depressive disorder is a clinical diagnosis where the individual has a persistently low or depressed mood. They can have difficulty experiencing pleasure, decreased interest in activities, feelings of extreme guilt or worthlessness, lack of energy, poor concentration, appetite changes, sleep disturbances, or suicidal thoughts.

MDD affects nearly 20 million American adults each year (over 7% of the US population).

What is Bipolar Disorder?

Bipolar disorder is general defined by extreme mood swings that include extremely high emotional states (mania or hypomania) as well as extremely low emotional states (depression).

It is a condition that affects over 1% of the population and has a significant impact on a person’s mood, energy, and ability to function.

What Happens to the Brain with Major Depressive Disorder and Bipolar Disorders?

It is important to understand that long periods of chronic stress, such as that which occurs in major depressive disorder (MDD) and bipolar disorder, can lead to the dysfunction of a neurotransmitter called glutamate.

Glutamate is important in several functions:

Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)
Maintenance of dendrite density (dendrites are small branches on neurons that receive signals from other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Additionally, chronic stress causes glutamate changes in the prefrontal cortex, amygdala, and hippocampus.

In the prefrontal cortex, this leads to dendritic shrinkage/impairment and impaired attention.
In the hippocampus, this can cause shrinkage of the hippocampus itself, dendriticshrinkage/impairment, and decreased ability for the individual to learn and maintain memory.
In the amygdala, this leads to overactivity of the structure, dendritic hypertrophy, and increased anxiety.

How Does Ketamine Treat MDD and Bipolar Disorder?

The exact mechanism of action of ketamine is not fully understood. However, broadly speaking, there are two major ways in which ketamine exerts its effects.

Short Term: Within the first couple hours of a ketamine infusion, a patient can feel ketamine’s anti-depressant effects. This is due to ketamine’s effects on the release of glutamate in the prefrontal cortex, hippocampus, and amygdala. This leads to rapid anti-depressive effects that occur within hours of treatment.
Long Term: Ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density lead to the longer term anti-depressive effects of ketamine.

Overall, ketamine rapidly facilitates synaptic plasticity and modifies neural function in the prefrontal cortex and hippocampus as well as reduces amygdala hyperreactivity to emotional stimuli. Because of ketamine’s effect on dendrite density (increasing the neuron’s ability to receive neurotransmitters), it works synergistically with other antidepressants (which work to increase the amount of neurotransmitters in specific regions of the brain).

How Effective is Ketamine for Depression and Bipolar Disorder?

While traditional antidepressant medications can take weeks to months for the body to respond, ketamine works within days of starting treatments. Additionally, the literature suggests that it has a response rate of 60-80% in treatment resistant depression (depression that has not responded to one medication from two different anti-depressant medication categories).

How Can I Find Out More Information?

For more information, Contact Us or submit a request for a 20 minute phone consultation.

Key Points:

Ketamine appears to be an effective and rapid treatment for suicidal ideation.
A single infusion of ketamine can reduce suicidal ideation for up to 6 weeks.
Ketamine works well alongside other medications for the treatment of suicidal ideation.

What is Suicidal Ideation?

Suicidal ideation refers to either thinking about or planning a suicide. These thoughts can be on a spectrum of severity from a wish to die with no plan or intent to active suicidal ideation with a specific plan and intent. Suicidal ideation does not have to include self-harm behaviors.

Self-harm is the behavior that is self-directed and deliberately results in the harm or potential injury of the individual. It includes both suicidal and non-suicidal self-injury as well as self-harm with unclear intent. Non-suicidal self injury is a significant risk factor for both suicide attempts and death by suicide and may or may not be accompanied by suicidal ideation.

Suicide is the 2 nd leading cause of death for adolescents and young adults aged 15-24 years old and the 10th leading cause of death overall in the United States.

Does Ketamine Decrease Suicidal Ideation?

The literature shows that ketamine produces safe rapid remission of suicidal ideation, increased feelings of safety, and decreased the likelihood of self-harm with just one infusion. These results are not just related to decreasing the severity of depression but also due to cognitive improvements (problem solving and clearer thinking). These effects occur in individuals who have not responded to other antidepressants.

How Long Do These Effects Last?

Antidepressant and decreased suicidal effects vary from individual to individual. Additionally, receiving a loading dose of ketamine (6 infusions over a period of a few weeks) will be far more effective than receiving just one infusion.

Studies that used just one infusion of ketamine found that the decreased suicidal ideation lasted as long as 6 weeks allowing for other vital treatments and resources to aid the individual struggling with suicidal thoughts.

How Does Ketamine Treat Suicidal Ideation?

The exact mechanism of action of ketamine is not fully understood. However, broadly speaking, there are two major ways in which ketamine exerts its effects.

First, within the first couple hours of a ketamine infusion, a patient can feel its anti-depressant effects. This is due to ketamine’s effects on the release of glutamate in the prefrontal cortex, hippocampus, and amygdala. This leads to rapid anti-depressive affects that occur within hours of treatment.
Second, ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in dendritic density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density leads to the longer term anti-depressive effects of ketamine.

Because of ketamine’s effect on dendrite density (increasing the neuron’s ability to receive neurotransmitters), it works synergistically with other antidepressants (which work to increase the amount of neurotransmitters in specific regions of the brain).

How Can I Find Out More Information?

For more information, Contact Us or submit a request for a 20 minute phone consultation.

SUICIDE HOTLINE:

If you or someone you know is contemplating suicide, please contact the National Suicide Prevention Lifeline (1-800-273-8255) or 988.

The National Suicide Prevention Lifeline is a 24-hour confidential suicide prevention service available to anyone in suicidal crisis or emotional distress. Their staff are specially trained in active listening skills and strategies for supporting people undergoing extreme emotional stress.

Key Points:

Generalized Anxiety Disorder is a common psychiatric diagnosis which includes excessive worry about a number of events for at least 6 months.
Ketamine appears to be effective for resistant Generalized Anxiety Disorder.
Patients with Generalized Anxiety Disorder may benefit from a full course of ketamine infusions.

What is Generalized Anxiety Disorder (GAD)?

Although it is normal to feel anxiety from time to time, generalized anxiety disorder (GAD) is usually defined by significant uncontrolled worrying about a number of events that occurs on most days and for at least 6 months.

GAD is associated with three (or more) of the following symptoms):

Restlessness or feeling on edge
Being easily fatigued
Difficulty concentrating or mind going blank
Irritability
Muscle tension
Sleep disturbances (difficulty falling or staying asleep, or restless, unsatisfying sleep)

Lifetime prevalence of GAD is 7.7% in women and just under 5% in men.

What is Treatment Resistant GAD?

Treatment resistant GAD is when an individual fails to respond to at least 1 trial of antidepressant therapy that has been given at an adequate dose and duration.

The literature suggests that between 30-50% of people undergoing treatment for GAD are “treatment resistant”.

What Causes Generalized Anxiety?

Although it is not fully understood why certain people suffer from GAD and others do not, generally, it develops when one is unable to cope well with their internal stress for a prolonged period. It can run in families, be due to medical conditions such as hyperthyroidism, and can sometimes be a side effect of a medication or substance abuse. GAD can be triggered by environmental stress as well as chronic illness.

Examining the brain’s structures, generalized anxiety as well as treatment resistant anxiety can lead to glutamate neurotransmitter imbalances.

Glutamate is important in several functions:

Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)
Maintenance of dendrite density (dendrites are small branches on neurons that receive signalsfrom other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Glutamate receptor damage can occur in the hippocampus and neuron breakdown can occur in the prefrontal cortex. Additionally, the amygdala (responsible for regulating fear and emotions) can be disproportionately enlarged and over-reactive. These changes decrease the patient’s ability to perform executive functions, maintain appropriate cognition, and regulate emotions

How Does Ketamine Treat Generalized Anxiety Disorders?

The exact mechanism of action of ketamine is not fully understood. However, broadly speaking, there are two major ways in which ketamine exerts its effects.

First, within the first couple hours of a ketamine infusion, a patient can feel its anti-anxiety effects. This is due to ketamine’s effects on the release of glutamate in the prefrontal cortex, hippocampus, and amygdala. This leads to rapid anti-depressive/anxiety affects that occur within hours of treatment.
Second, ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density leads to the longer-term anti-anxiety effects of ketamine.

Additionally, the literature has shown that ketamine infusion therapy results in several neurocognitive improvements for most people. These include faster processing speed, improved visual learning, and improved memory.

How Effective is Ketamine for Generalized Anxiety Disorders?

Although there is less research on ketamine for generalized anxiety disorders compared to depression, a 2022 systematic review on ketamine treatment for treatment resistant anxiety found that a single dose of ketamine has rapid acting mood enhancing and anxiolytic effects that persist up to a week after treatment.

It is important to note that receiving a loading dose of ketamine (6 infusions over a period of a few weeks) has been shown to be far more effective than just a single treatment of ketamine.

How Can I Find Out More Information?

For more information, Contact Us or submit a request for a 20 minute phone consultation.

Key Points:

PTSD is a psychiatric disorder which follows a traumatic event.
PTSD is thought to result from changes in neurotransmitters and key brain structures/regions.
Ketamine has a long history of use in traumatic situations beginning with wartime injuries.
Ketamine appears to be effective in the treatment of PTSD.

What is Post-Traumatic Stress Disorder?

Post-Traumatic Stress Disorder (PTSD) is one of the five major types of anxiety disorders and can develop after exposure to terrifying events where significant physical harm occurs or was threatened. Following the event, recurrent, involuntary, and intrusive distressing memories/dreams/reactions occur. The duration of these disturbances last more than 1 month long. Examples of traumatic events that could trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, or military combat.

The lifetime prevalence of PTSD among adults in the United States is about 6%. Along with PTSD comes a significant clinical, social, and economic burden.

What Causes PTSD?

PTSD can develop after extremely stressful, frightening, or distressing events or after prolonged traumatic experiences. Examples of events that can lead to PTSD include:

Serious accidents
Physical or sexual assault
Abuse
Life threatening health problems
Childbirth experiences
War and battlefield exposure
Torture

When we look at the pathophysiology of PTSD, there are two major changes that occur:

1) Inappropriately high stress hormones

Although the precise pathophysiology of PTSD is not clear, studies have shown that those who suffer from PTSD have abnormally high levels of stress hormones. These hormones, like adrenaline, are usually released in short bursts known as the “fight or flight” response. Those with PTSD continue to produce these chemicals even when there is no danger.

2) Changes in brain structures:

Additionally, structures of the brain that process emotions appear different on brain scans. The hippocampus, responsible for memory and emotions, appears smaller in size. The literature suggests that these changes may relate to fear, anxiety, memory problems, and flashbacks. The poorly functioning hippocampus may cause inappropriate processing of these memories that lead to a sustained level of anxiety.

How Does Ketamine Treat PTSD?

It is believed that a neurotransmitter called glutamate plays a key role in the pathogenesis of PTSD.

Glutamate is important in several functions:

Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)
Maintenance of dendrite density (dendrites are small branches on neurons that receive signals from other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Chronic stress significantly impacts glutamate transmission.

Although the exact mechanism of action of ketamine is not fully understood, broadly speaking, there are two major ways in which ketamine exerts its effects.

First, within the first couple hours of a ketamine infusion, the release of glutamate is effected in key areas of the brain including the hippocampus.
Second, ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density, especially in the hippocampus. This can lead to increased functionality of the hippocampus and cause more appropriate processing of memories.

How Effective is Ketamine Infusion Therapy for PTSD?

The literature suggests that current pharmacological treatments are ineffective in about 40% of patients. Ketamine appears to be a novel treatment for refractory and disabling cases of PTSD given its effectiveness in both decreasing the likelihood and symptoms of PTSD.

Ketamine’s use in war time on solders injured in battle have led to several studies examining the relationship between ketamine administration (by medics to provide pain relief during acute medical intervention) and decreased PTSD diagnoses following the injury. Several studies have shown that, when comparing ketamine administration compared to morphine administration to treat battle injuries, soldiers treated with ketamine had lower rates of PTSD diagnosis the following year.

This has led to further study of ketamine infusions to treat diagnosed and resistant cases of PTSD. The literature indicates that a single dose of ketamine produces rapid and significant decreases in PTSD symptoms that remain for at least 2 weeks. Ketamine was also associated with decreased depression symptom severity and overall improvement of the individuals’ clinical presentation.

It is important to note that receiving a loading dose of ketamine (6 infusions over a period of a few weeks) has been shown to be far more effective than just a single treatment of ketamine.

How Can I Find Out More Information?

For more information, Contact Us or submit a request for a 20 minute phone consultation.

Key Points:

Obsessive Compulsive Disorder is a psychiatric diagnosis characterized by frequent intrusive thoughts and images and accompanying mental rituals or physical acts to reduce anxiety.
Many patients with OCD fail to respond to serotonin medications alone (SSRIs).
OCD may also be modulated by glutamate receptors.
In preliminary studies, ketamine combined with exposure based psychotherapy produced reduction in OCD symptoms.

What is Obsessive Compulsive Disorder (OCD)?

Obsessive compulsive disorder is one of the five major types of anxiety disorders and is a condition where the individual has frequent intrusive thoughts and sensations that cause them to perform tasks repetitively. These compulsions cause significant interference with social interactions and the performance of daily tasks.

It is estimated that the lifetime prevalence of OCD is between 2-3%.

What Causes OCD?

It is uncertain what exactly causes OCD. We do know that genetics, brain abnormalities, and environment shape the likelihood of OCD occurring. It is also common for other anxiety disorders, depression, eating disorder, or substance abuse to occur with OCD.

It has been shown in the literature that a significant proportion of individuals do not respond to selective serotonin reuptake inhibitors (SSRIs) indicating the serotonergic dysfunction that occurs in OCD does not fully explain the illness. Magnetic resonance spectroscopy, cerebrospinal fluid, genetic studies, and animal models of OCD have found evidence of dysfunction related to a neurotransmitter called glutamate.

Glutamate is important in several functions:

Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)
Maintenance of dendrite density (dendrites are small branches on neurons that receive signalsfrom other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Structurally, OCD is associated with dysfunction in two frontal cortical regions:

The orbitofrontal cortex (OFC)
The dorsal anterior cingulate cortex (dACC)

These regions have consistently been shown to be hyperactive at rest in adults with OCD compared to healthy adults, increased in activity with increased OCD symptoms, and no longer hyperactive following successful treatment.

How Does Ketamine Treat OCD?

The exact mechanism of action of ketamine is not fully understood. However, we do know that:

In the first couple hours of a ketamine infusion, the release of glutamate is significantly effected in key areas of the brain.
Ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion leading to increased functionality of brain structures

Additionally, ketamine has inhibiting/normalizing effects on both the orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) – two areas of the brain in which their hyperactivity is believed to lead to OCD symptoms.

How Effective is Ketamine Infusion Therapy for OCD?

Although there is less research on ketamine for OCD compared to depression, a small open-label study of patients with OCD found that a single dose of ketamine added to exposure-based cognitive behavioral therapy led to an initial reduction in OCD symptoms and was sustained for over two weeks. The study suggests that ketamine can have a synergistic effect on other OCD related treatments.

Other studies have shown similarly that a single dose of ketamine rapidly and dramatically decreased OCD thoughts and lasted for at least one week.

It is important to note that receiving a loading dose of ketamine (6 infusions over a period of a few weeks) has been shown to be far more effective than just a single treatment of ketamine.

How Can I Find Out More Information?

For more information, Contact Us or submit a request for a 20 minute phone consultation.

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