IV Ketamine

What is Ketamine?

While ketamine was originally used as an anesthetic agent in the 1970s, by the 1990s scientists started to recognize that some individuals who received ketamine for anesthesia were having profound mental health improvements. Since then, the use of Ketamine for depression has been a rapidly growing area of interest in the field of mental health, particularly for patients with treatment-resistant depression (TRD)—depression that hasn’t improved with traditional antidepressant medications or therapies. Although Ketamine is currently not FDA approved as an antidepressant, years of research has supported its benefit in a variety of mental health conditions. 

How Does IV Ketamine Work for Depression?

Ketamine is believed to have a different mechanism of action compared to traditional antidepressants. While most antidepressants (like SSRIs and SNRIs) work by increasing the availability of neurotransmitters such as serotonin and norepinephrine in the brain over time, ketamine works more rapidly and through different pathways:

1. NMDA Receptor Blockade: Ketamine primarily blocks the NMDA receptors in the brain. These receptors are involved in the signaling of glutamate, which is the brain’s most abundant excitatory neurotransmitter. By blocking NMDA receptors, ketamine modulates the glutamate system, which leads to an increase in synaptic connections and the promotion of neuroplasticity (the ability of the brain to reorganize itself by forming new neural connections). This is a crucial feature, as it’s thought that chronic depression can impair these neural connections, and ketamine helps to “reset” them.
2. Rapid Antidepressant Effects: Unlike traditional antidepressants, which typically take weeks to show effects, IV ketamine can have rapid effects, often within hours after a single infusion. Many people report feeling a significant improvement in mood and a reduction in depressive symptoms shortly after receiving the treatment.
3. Glutamate and Brain Plasticity: By enhancing glutamate signaling, ketamine promotes brain plasticity, which helps reverse some of the changes caused by depression, particularly in brain regions such as the prefrontal cortex, which is involved in mood regulation, decision-making, and emotional responses.
4. Restoring Connections in the Brain: Ketamine increases the production of BDNF (brain-derived neurotrophic factor), which helps promote the growth of new neurons and synapses. This growth is thought to reverse the neural changes that depression causes in key areas of the brain.

How IV Ketamine is Administered

IV ketamine is typically administered in a clinical setting by healthcare professionals, particularly in specialized ketamine infusion centers. The process involves:

1. Infusion Process:
   • The patient receives an IV infusion of ketamine, which is typically administered over a period of 40 minutes to an hour.
   • During the infusion, the patient is monitored for any side effects or changes in heart rate, blood pressure, and mental state.
   • The dosage is generally low (compared to recreational or anesthetic doses) and is tailored to the patient’s specific needs.
   • Patients are monitored for a total of 2 hours to ensure that they tolerate the treatments well and have fully returned to baseline before discharge.
   • Please note that individuals may continue to experience cognitive slowing or other alterations after completing their infusions.  Therefore, you must not drive the remainder of the day after your infusion and you must have arrangements made in advance for a ride home after your treatments.
2. Frequency:
   • The frequency of IV ketamine infusions can vary based on the patient’s condition and response to treatment. Typically, patients may receive 2-3 treatments per week when they start.  This can then be decreased to once per week after the first 4 weeks.
   • As improvement is seen, the frequency of sessions may further decrease to once a month, or as needed for maintenance.
3. Monitoring:
   • Patients are closely monitored during the infusion due to potential side effects like changes in heart rate or blood pressure.
   • Many patients experience some dissociative effects (feeling detached from their body or reality), but these are usually short-lived and resolve once the infusion ends.
   • Some centers offer psychotherapy alongside ketamine infusions to help the patient process emotions and experiences while in the altered state induced by ketamine.

Effectiveness of IV Ketamine for Depression

• Rapid Onset of Action: One of the most remarkable aspects of IV ketamine for depression is its rapid onset. Unlike traditional antidepressants, which take weeks to show effectiveness, ketamine often provides immediate relief. Many patients report feeling an improvement in mood and a reduction in suicidal thoughts after just one infusion.
• Treatment-Resistant Depression: IV ketamine has shown particular promise for treatment-resistant depression—a condition in which conventional medications like SSRIs or SNRIs fail to provide adequate relief. For people who have not responded to other therapies, ketamine offers a new option with the potential to provide rapid improvement.
• Sustained Improvement: Some studies have found that the effects of ketamine can be sustained with repeated infusions, and many patients experience significant symptom relief over time. However, the duration of relief can vary from person to person, with some requiring ongoing infusions to maintain the benefits, while others may experience longer-term improvement.

Safety and Side Effects of IV Ketamine

Though IV ketamine is generally considered safe when administered in a controlled medical setting, it can cause side effects, particularly during the infusion process. Some common and less serious side effects include:

1. Dissociation and Hallucinations: Some patients experience a dissociative state during the infusion, where they feel detached from their body or reality. This is temporary and generally resolves once the infusion ends. However, it can be unsettling for some.
2. Increased Blood Pressure: Ketamine can increase heart rate and blood pressure, which is usually closely monitored during treatment to prevent complications, particularly in patients with cardiovascular issues.
3. Nausea or Vomiting: Some patients may feel nauseous or even vomit during or after the infusion, although this is relatively rare.
4. Cognitive Effects: In the short term, ketamine can cause some cognitive side effects such as confusion, dizziness, or memory impairment. However, these typically resolve quickly after the infusion ends.
5. Potential for Abuse: Although the doses used for depression treatment are much lower than those used recreationally, there is still a risk of dependency or abuse if not used appropriately. This is why it’s crucial that ketamine is administered under the supervision of trained healthcare providers.

Alternative Forms of Ketamine for Depression

In addition to IV ketamine, there are other methods of administering ketamine for depression treatment:

• Intranasal Ketamine (Spravato): The FDA has approved an intranasal form of ketamine called Spravato for treatment-resistant depression. It is administered under the supervision of a healthcare provider, and it offers another option for patients who cannot receive IV ketamine.
• Oral Ketamine: In some cases, oral ketamine may be used, although it is less commonly prescribed for depression treatment compared to IV or intranasal forms.

What is the difference between IV Ketamine and Spravato?

When we use the term “Ketamine,” we are typically referring to a racemic mixture meaning it contains two mirror-image molecules: R-ketamine and S-ketamine.  This is the form that was originally used as an anesthetic, and which is currently only approved as an anesthetic agent.  However, this does not mean that it ineffective for depression, it simply means that there are no large-scale, multi-center studies needed for FDA approval.  Ketamine can be administered intravenously (IV), intramuscularly (IM), sublingual (SL), or intranasal (IN). Because Ketamine is not FDA approved, it is not covered by insurance and must be paid for out of pocket. Spravato contains only the S-enantiomer of ketamine called Esketamine (but not the R-Ketamine).  It is believed that the Esketamine is a more effective antidepressant.  Spravato, or Esketamine, is currently FDA approved for treatment resistant depression either with or without an oral antidepressant, or for MDD with suicidal ideation.  Because Spravato is FDA approved, it is covered by most major insurances.