Depression Therapy Ketamine Therapy

Spravato vs. Ketamine: Which is Better for Treatment-Resistant Depression?

6 min read

Spravato vs Ketamine – what’s the difference?

Depression is a pervasive mental health condition that affects millions of people worldwide. For many, traditional treatments such as antidepressants and psychotherapy offer significant relief. However, a subset of patients, often referred to as having treatment-resistant depression (TRD), do not respond to these conventional therapies. This has led to increased interest in alternative treatments, such as Spravato (esketamine) and ketamine. Both have shown promise, but how do they compare? This article explores the differences and similarities between Spravato and ketamine, and their respective roles in treating TRD.

What is Ketamine?

Ketamine is an anesthetic that has been used in medical settings for decades. Originally developed in the 1960s, it is widely known for its use in surgery and pain management. More recently, ketamine has been discovered to have rapid-acting antidepressant effects, especially in individuals with TRD.

Ketamine is typically administered intravenously (IV) in a clinical setting. Patients receive the treatment under the supervision of medical professionals, ensuring their safety throughout the process. The effects of ketamine can be felt within hours, offering quick relief from depressive symptoms. This is particularly beneficial for patients who have not found success with other treatments.

What is Spravato?

Spravato, also known as esketamine, is a derivative of ketamine. Approved by the FDA in 2019, Spravato is specifically designed to treat TRD. Unlike traditional ketamine, which is administered via IV, Spravato is given as a nasal spray. This method of administration can be more convenient and less invasive for patients.

Spravato is used in conjunction with an oral antidepressant. Patients self-administer the nasal spray under the supervision of a healthcare provider, who monitors them for at least two hours after administration. This is to ensure the patient’s safety, as Spravato can cause side effects such as dizziness, dissociation, and increased blood pressure.

What Are the Differences Between Ketamine and Esketamine Treatments?

Both Spravato and ketamine have shown effectiveness in treating TRD, but their mechanisms and results can vary. Here is a comprehensive comparison of their efficacy:

Comparing Spravato vs. Ketamine

AspectKetamine IV InfusionsSpravato (Esketamine) Treatments
Method of DeliveryAdministered via IV over 40 minutes, allowing precise control and enhanced cognitive effects.Self-administered nasal spray in two to three doses with five-minute intervals; suitable for those avoiding IV.
Insurance CoverageTypically, insurance covers the psychiatric care at the clinic, but not the ketamine infusion itself, leading to out-of-pocket expenses.Insurance often covers Spravato, with prior approval. Patient costs may be minimal, potentially as low as $0 per treatment.
BioavailabilityIV administration ensures 100% bioavailability, meaning the full dose reaches the brain.Nasal spray has around 50% bioavailability; some medication may remain in nasal passages or be swallowed, reducing brain delivery.
Treatment ScheduleSix infusions over 2-3 weeks, with maintenance boosters as needed. Frequency varies from monthly to biannually based on response.Initial phase: twice weekly for 4 weeks, followed by once weekly for weeks 5-8, then every 2 weeks or as needed.
DosageDosage is weight-based (Kg) and adjusted for consistency and comfort.Available in 56mg and 84mg doses, with selection based on patient response.
Eligible Disorders TreatedMajor Depressive Disorder, various forms of Treatment-Resistant Depression, PTSD, Anxiety Disorders, Bipolar Disorder, Substance Abuse.FDA-approved for Major Depressive Disorder and Acute Suicidality.
Medication RequirementsCan be administered alone or alongside other psychiatric medications.Must be combined with an oral antidepressant.
Length of AppointmentTypically between 90 and 120 minutes.Approximately 2.5 hours.

As seen in the table, both treatments offer rapid relief from depressive symptoms, which is a significant advantage for patients with TRD. However, their methods of administration and associated costs can differ.

Mechanisms of Action

The exact mechanisms by which Spravato and ketamine alleviate depression are not fully understood, but both are believed to involve the brain’s glutamate system. Glutamate is a neurotransmitter that plays a crucial role in neural activation. By modulating glutamate activity, these treatments may help restore synaptic connections in brain areas associated with mood regulation.

Spravato works on the NMDA receptor, a specific type of glutamate receptor, to produce its antidepressant effects. It is thought to create changes in brain connectivity that help alleviate depressive symptoms.

Ketamine also targets the NMDA receptor but can have broader effects due to its molecular structure. This might explain why some patients respond better to ketamine than to Spravato, or vice versa.

Side Effects and Safety

Both Spravato and ketamine can cause side effects, though they are generally well-tolerated when administered under medical supervision.

Common side effects of Spravato include:

  • Dizziness
  • Nausea
  • Dissociation (a feeling of being detached from reality)
  • Increased blood pressure
  • Sedation

Common side effects of ketamine include:

  • Dizziness
  • Nausea
  • Dissociation
  • Increased blood pressure
  • Hallucinations

Patients receiving either treatment are monitored for at least two hours post-administration to ensure their safety and manage any adverse effects.

Cost Comparison – Spravato vs Ketamine

The cost of treatment can be a significant factor for many patients. Spravato is generally more expensive than ketamine, primarily due to its newer status and the specific clinical setup required for administration. However, Spravato is FDA-approved for TRD, which means it is more likely to be covered by insurance compared to ketamine, which is often used off-label for depression.

Ketamine treatment costs can vary widely, depending on the clinic and region. Some insurance plans may cover ketamine treatments, but coverage is not as consistent as it is for Spravato.

Convenience and Accessibility

When considering treatment options, convenience and accessibility are important factors.

Spravato offers the convenience of a nasal spray, which can be easier and less invasive than IV administration. However, patients still need to visit a clinic for each session, where they are monitored for at least two hours.

Ketamine requires an IV infusion, which some patients may find more invasive. Treatment sessions also require clinical supervision, similar to Spravato, to monitor for side effects and ensure patient safety.

Long-term Use and Sustainability

Both treatments can require ongoing administration to maintain their antidepressant effects.

Spravato is typically administered twice a week for the first month, then once a week or once every two weeks thereafter, depending on the patient’s response.

Ketamine treatment schedules can vary, with some patients receiving infusions multiple times per week initially, followed by maintenance treatments at less frequent intervals.


Both Spravato and ketamine have emerged as valuable options for treating treatment-resistant depression, offering rapid relief for patients who have not found success with traditional therapies. While they share some similarities, they differ in administration methods, cost, and insurance coverage.

Marpa Minds offers Spravato treatment in Westchester Country, providing patients with access to cutting-edge therapies tailored to their needs. Whether choosing Spravato or ketamine, it is crucial for patients to work closely with their healthcare providers to determine the best course of action for their individual circumstances.

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