IV Ketamine vs Spravato vs Lozenges: How the Three Compare

01How Does IV Ketamine Compare to Spravato?

IV ketamine and Spravato are both well-supported, closely supervised options, but they differ in dosing control, FDA status, and insurance. IV delivery lets a clinician titrate the dose precisely and adjust in real time, and it has a long research history, but it is used off-label and is typically self-pay. Spravato is FDA approved specifically for treatment-resistant depression, which gives it a clearer insurance pathway, and it is delivered as a nasal spray with a required monitoring period in a certified setting.

For someone prioritizing precise dosing and the broadest evidence, IV is often favored. For someone who needs an insurance-eligible route and meets the FDA-approved criteria, Spravato can be the better fit. Neither is universally superior; they suit different priorities.

02Where Do Sublingual Lozenges Fit?

Sublingual lozenges are the most accessible and lowest-cost form, often used in at-home programs, but they deliver lower and less precisely absorbed doses, and the evidence base is less developed than for IV or Spravato. Absorption under the tongue varies between people, so the effective dose is harder to control than with IV.

Lozenges can be a reasonable option for lower-risk patients who value convenience and consistency, especially as a maintenance approach. For severe or treatment-resistant cases, many clinicians lean toward the more controlled forms, at least to start. The deeper tradeoff between supervised and remote care is covered in our at-home vs in-clinic ketamine guide.

03Which Form Has the Best Evidence?

IV ketamine has the longest and deepest research record for treatment-resistant depression, and esketamine (Spravato) carries FDA approval for that indication based on its own trials, so those two have the strongest evidence. Sublingual ketamine is supported by growing but more limited data. When evidence quality is the deciding factor, IV and Spravato lead.

Evidence is only one input, though. The form you can access, afford, and follow consistently also shapes real-world results, which is why this is a shared decision rather than a ranking to memorize.

04Which Should I Choose?

The right form depends on your diagnosis, medical history, insurance situation, and how much monitoring you need, which is why this is decided with a provider, not in advance. As a rough guide: choose IV for precise dosing and the strongest evidence when paying out of pocket, consider Spravato if you want an insurance-eligible, FDA-approved route and qualify, and consider lozenges for lower-risk, convenience-focused or maintenance care. Cost often drives this decision, so it helps to read our ketamine therapy cost breakdown alongside it.

This article is for general educational purposes only and is not medical advice. It does not create a provider-patient relationship. Talk with a qualified Florida-licensed clinician about your individual situation.