What is the Best Form of Ketamine? IV vs Nasal

The Latest Research Shows IV Ketamine Is More Effective for Depression Relief

Studies from 2021, 2022, 2023, 2024, and 2025 consistently show both IV and intranasal esketamine are effective in relieving depression. The difference is that IV is typically faster and more effective in treating symptoms of depression.

The latest study specifically showed patients experienced:

• 10% better improvement in depression symptoms with IV ketamine
• Faster time to symptom relief with IV ketamine compared to nasal esketamine

Most patients found improvement after just 1 treatment with IV ketamine. Intranasal esketamine was not too far behind, with improvement after 2 sessions.

Both ketamine treatments work far faster than traditional antidepressants, but IV ketamine demonstrated superior efficacy and speed in this real-world clinical setting

Understanding Treatment-Resistant Depression

Treatment-resistant depression (TRD) affects approximately 30% of people with major depression—those who haven't responded adequately to at least two different antidepressant medications. For these individuals, ketamine represents a genuine breakthrough.

Unlike traditional antidepressants that take 4-8 weeks to work, ketamine acts through the glutamate system, producing rapid changes in brain connectivity that can relieve symptoms within hours or days.

Why IV Ketamine Performs Better

IV Ketamine is believed to perform better than all other forms of ketamine, including lozenges and subcutaneous injections. Here's why:‍

• ‍Pharmacokinetics: IV = 100% bioavailability and tight dose-rate control
  
  • ‍Nasal esketamine ~50% bioavailability with higher inter-subject variability
• ‍Dosing flexibility: IV allows for precise dose titration and adjustment for safety and efficacy — an approach supported by expert guidance
• Rapid side effect treatment: IV allows rapid treatment of nausea, headache, and other side effects
• Not limited to depression: IV Ketamine can be used for bipolar depression, PTSD, anxiety, or chronic pain

When Intranasal Esketamine (Spravato) Makes Sense

Despite IV ketamine's superior performance, esketamine has real advantages:

• ‍Insurance Coverage: Spravato is FDA-approved specifically for treatment-resistant depression, making insurance coverage more likely (though prior authorization is usually required)
• ‍No Needles Required: If you have needle phobia or difficult venous access, intranasal administration is much easier
• Depression previously diagnosed: Most insurances will cover Spravato for depression, but not bipolar depression, anxiety, PTSD, or chronic pain.

Is IV or Nasal Ketamine Right for You?

Choose IV Ketamine if:

• You want maximum efficacy and fastest results
• You want the fastest treatment for side effects (nausea, etc.)
• Insurance coverage is comparable or unavailable for esketamine (anxiety, PTSD, bipolar depression, etc.)

Consider Intranasal Esketamine if:

• Your insurance covers esketamine and you qualify for treatment-resistant depression
• You want to avoid needles

Start Treating Your Depression Today

The research is clear: IV ketamine offers superior efficacy and faster onset than intranasal esketamine for treatment-resistant depression. However, both treatments work well, and the best option is the one you can access and afford.

Many patients achieve excellent results with either treatment. The key is starting therapy with a qualified provider who can monitor your progress and adjust treatment as needed. Clarus Health offers both IV Ketamine and Spravato to help you make a personalized decision based on your specific situation. Contact Clarus Health today to speak with a doctor and start rapidly treating your depression.