Is ketamine, specifically racemic ketamine, FDA-approved for the treatment of Major Depressive Disorder (MDD) or other depressive disorders like Treatment-Resistant Depression (TRD)? And if not ketamine itself, is any derivative or formulation of ketamine, such as esketamine (Spravato), FDA-approved for these conditions? If any formulation is approved, what are the specific indications, dosages, and required treatment protocols, including monitoring requirements, associated with its use? What are the key differences in the FDA approval status and usage guidelines between ketamine and its derivatives in the context of treating depression?

Answer

Yes, ketamine is FDA-approved for the treatment of depression, but with limitations.

Specifically:

• Esketamine (Spravato): The FDA has approved esketamine, a nasal spray form of ketamine, under the brand name Spravato, for treatment-resistant depression (TRD) in adults. TRD is defined as depression that has not responded to at least two different antidepressant medications. It is also approved for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.
• Important Considerations for Esketamine (Spravato) Use:
  • Spravato must be administered under the supervision of a healthcare provider in a certified doctor’s office or clinic.
  • Patients are monitored for at least two hours after administration due to the risk of sedation, dissociation, and increases in blood pressure.
  • Spravato is only available through a restricted distribution system.
  • It is used in conjunction with an oral antidepressant.
• Ketamine (Off-Label Use): While ketamine itself (not esketamine) is not FDA-approved for depression, it is sometimes used "off-label" by doctors to treat depression. "Off-label" means using an approved drug for a condition or in a way that is not officially approved by the FDA. This is a legal and common practice, but it’s important to understand that the FDA has not evaluated the safety or effectiveness of ketamine for depression when used in this way.
• Infusion Clinics: Many ketamine infusion clinics have emerged, offering intravenous ketamine infusions for depression and other mental health conditions. These clinics operate under the "off-label" use of ketamine.
• Safety and Efficacy Concerns (Off-Label Use):
  • There are concerns about the long-term safety and efficacy of repeated ketamine infusions for depression.
  • Potential side effects include cardiovascular issues, cognitive problems, and substance abuse.
  • Guidelines for off-label ketamine use vary, and the quality of care can differ significantly between clinics.

In summary, esketamine (Spravato) is FDA-approved for specific types of depression under strict medical supervision. Ketamine itself is not FDA-approved for depression, but it’s used off-label, raising safety and efficacy considerations.