If you are exploring rapid-acting therapies for treatment-resistant depression, you will inevitably come across the terms “esketamine” and “Spravato” and wonder how they differ from standard ketamine.
Traditional ketamine (often referred to clinically as “racemic ketamine”) is composed of two mirror-image molecules. Esketamine is simply a subcomponent of standard ketamine. When pharmaceutical researchers isolated this specific molecule, they formulated it into an intranasal (IN) medication, meaning it is administered as a nasal spray rather than through an intravenous (IV) drip.
Spravato is the commercial brand name for this esketamine nasal spray. Manufactured by the pharmaceutical company Janssen, Spravato holds a unique and powerful distinction in the psychiatric world: it is the only FDA-approved nasal spray for treatment-resistant depression in adults.
This FDA approval is the defining difference between Spravato and traditional IV ketamine. While IV ketamine has decades of clinical research proving its antidepressant effects, it was originally approved by the FDA strictly as an anesthetic. Therefore, using IV ketamine for depression is considered an “off-label” treatment.
Both IV ketamine and Spravato (IN esketamine) are highly effective tools for combating severe depression. A recent study comparing the two treatments found that IN esketamine resulted in a 39.55% reduction in depression scores, while IV ketamine showed a slightly greater overall efficacy with a 49.22% reduction. Additionally, while IV ketamine often produces symptom improvement immediately after the first dose, Spravato patients typically experience significant improvements after their second treatment.
Because Spravato carries official FDA approval for depression, it has a massive accessibility advantage over off-label IV ketamine: it is covered by most major commercial insurance plans as well as Medicare Part B.
- Without insurance: Spravato is highly expensive. The drug alone costs between $700 and $1,200 per dose depending on the strength (starting at 56 mg and often stepping up to 84 mg), and this does not include the clinic’s fee for the required two-hour observation period.
- With insurance: Coverage dramatically changes the landscape. Patients who meet their deductible often pay between $10 and $125 per session, making it a viable option for those who cannot afford the high out-of-pocket costs of off-label IV ketamine.
Unlike IV ketamine, which can have more flexible dosing, Spravato treatment follows a rigid, FDA-approved schedule. The process begins with an induction phase of eight sessions (two per week) over the first four weeks, which is when patients typically begin to see symptom improvement. This is followed by a maintenance phase of one session per week for the next four weeks, eventually tapering down to once every other week.
Ultimately, whether you and your psychiatrist choose IV ketamine or the FDA-approved Spravato will depend on a holistic combination of your clinical needs, insurance coverage, and logistical availability.
Learn more about depression on the blog here.
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