From the Guidelines
Ketamine is a recommended treatment option for patients with major depressive disorder who have not responded to several adequate pharmacologic trials, as suggested by the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline. This recommendation is based on the current evidence that both ketamine infusion and intranasal esketamine improve depressive symptoms in patients with MDD for whom at least 2 previous adequate trials of antidepressant medications have failed 1.
Key Points to Consider
- Ketamine is typically administered as an intravenous infusion at doses of 0.5-1.0 mg/kg over 40 minutes, with patients usually receiving a series of 6 treatments over 2-3 weeks, followed by maintenance treatments as needed.
- Some clinics also offer intranasal esketamine (Spravato), which is FDA-approved specifically for treatment-resistant depression.
- Ketamine works differently than conventional antidepressants by targeting the glutamate system rather than serotonin, potentially providing rapid relief within hours to days rather than weeks.
- Side effects during treatment may include dissociation, dizziness, nausea, and increased blood pressure, which typically resolve quickly after the infusion ends.
- Treatment requires medical supervision and isn't suitable for everyone, particularly those with certain cardiovascular conditions, psychosis, or substance use disorders.
Important Considerations for Treatment
- Ketamine lacks long-term efficacy and safety trials in MDD, and the bulk of the evidence on short-term (7-day) efficacy is from studies in patients who have previously not responded to adequate trials of antidepressants.
- Although there is evidence to support longer-term maintenance use of esketamine, it too has been primarily studied in patients who have previously not responded to trials of antidepressants.
- Unlike ketamine, esketamine has risk evaluation and mitigation strategy requirements, which include requirements for pharmacy, health care setting certification, and mandatory monitoring for 2 hours after treatment.
Recommendation
Ketamine and esketamine are not recommended as initial treatment but are reserved for patients for whom previous therapies have failed or who have not tolerated previous therapies 1. While ketamine shows promise, it's generally considered after other treatments have failed, and insurance coverage remains limited, with treatments often costing $400-800 per infusion out-of-pocket.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Ketamine as a Treatment for Depression
- Ketamine is an anesthetic drug that has been found to be effective in treating depression, particularly treatment-resistant depression (TRD) 2, 3, 4, 5, 6.
- The exact mechanisms of ketamine's antidepressant effects are not fully understood, but it is thought to involve the blockade of N-methyl-D-aspartate (NMDA) receptors and the activation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 3, 4, 6.
- Ketamine has been shown to have rapid and robust antidepressant effects, often within hours of administration, and can be effective in patients who have not responded to traditional antidepressant medications 2, 3, 4, 5, 6.
Administration and Efficacy
- Ketamine can be administered intravenously or intranasally, with intravenous administration being more bioavailable 3.
- Studies have shown that ketamine can be effective in treating both acute and chronic depression, as well as depression that is comorbid with chronic pain 3, 5.
- The efficacy of ketamine in treating depression has been demonstrated in several clinical trials, including a study that found that combination therapy with transcranial magnetic stimulation (TMS) and ketamine was effective in treating TRD 2, 5.
Safety and Side Effects
- Ketamine has been associated with several side effects, including dissociation, hallucinations, and abuse potential 4.
- The long-term safety and efficacy of ketamine in treating depression are not yet fully understood and require further study 4, 5.
- Despite these concerns, ketamine has been approved for use in treating TRD in conjunction with an oral antidepressant in the United States and Europe 4.