Nearly 3 million adults in the United States experience treatment-resistant depression (TRD), a form of major depressive disorder that does not respond to multiple treatment attempts. Interest has grown around the use of ketamine and esketamine, drugs originally developed as anesthetics, for patients who have not found relief through standard therapies.
“These medications can be revolutionary,” said psychiatrist Sohag Sanghani, MD, at Northwell’s Zucker Hillside Hospital. “They can provide fast relief to patients who have suffered for years.”
Both ketamine and esketamine target the same area in the brain but differ in several key ways. Ketamine is not approved by the Food and Drug Administration (FDA) for TRD, which may affect insurance coverage and out-of-pocket costs for patients. In contrast, esketamine received FDA approval for TRD in 2019 and is covered by many insurance plans, potentially making it more accessible financially. Esketamine’s approval applies only to unipolar depression; available research suggests ketamine may be effective for both unipolar and bipolar depression.
The method of administration also varies between the two drugs. Ketamine is delivered via a slow intravenous infusion over about 40 minutes, while esketamine is administered as a nasal spray over 10 to 15 minutes. However, patients receiving esketamine require at least two hours of post-administration monitoring compared to approximately 90 minutes following a ketamine infusion.
Dosage flexibility presents another distinction. With ketamine infusions, dosing can be tailored according to patient weight and adjusted during administration if side effects arise. “If side effects appear, we can interrupt the infusion or adjust the dose,” Dr. Sanghani explained. “Esketamine is only available in two doses, and the entire dose is administered at once — it can’t be interrupted or adjusted.”
Dr. Sanghani emphasized that either medication could offer significant help to those experiencing severe forms of depression: “they can be really helpful for those with the worst cases of depression.”
