Intranasal Ketamine vs. IV Ketamine Therapy: What Therapists Need to Know

www.propeltherapeutics.com

For patients with treatment-resistant depression, PTSD, or chronic pain, ketamine has emerged as one of the most exciting advances in mental health care in decades. Yet not all ketamine treatments are the same.

Two of the most widely used delivery methods are intranasal ketamine (often prescribed as compounded sprays or the FDA-approved esketamine nasal spray) and intravenous (IV) ketamine infusions.

While both can help patients break through depressive and pain cycles, they differ in bioavailability, dosing precision, speed of onset, and clinical use cases—differences that matter when deciding the right treatment for your patient.

1. Bioavailability: How Much Ketamine Reaches the Brain

• Intranasal ketamine:

  • Bioavailability is typically 25–50%.

  • Dose absorption can vary widely depending on nasal anatomy, mucosal health, and patient technique.

  • Peaks in blood levels can be inconsistent from one administration to the next.

• IV ketamine:

  • Nearly 100% bioavailability because it’s delivered directly into the bloodstream.

  • Allows for precise, reproducible dosing every time.

  • Ensures consistent therapeutic levels in the brain.

Why it matters: Inconsistent absorption from intranasal dosing can make it harder to predict therapeutic outcomes, especially in patients with severe or urgent symptoms.

2. Onset and Duration of Effect

• Intranasal ketamine:

  • Onset: 5–20 minutes.

  • Gradual rise in effect; may be less abrupt for patients sensitive to rapid changes.

  • Duration: Effects can last hours to days, but some patients require multiple weekly doses to maintain benefit.

• IV ketamine:

  • Onset: Often within minutes during the infusion.

  • Allows for immediate monitoring of effects and symptom changes.

  • Duration: Benefits can last days to weeks after a full course of 6–8 infusions.

Why it matters: For patients in acute crisis—especially those with suicidal thoughts—speed can be a deciding factor.

3. Dosing Control and Flexibility

• Intranasal ketamine:

  • Fixed dosing per spray; less ability to titrate mid-session.

  • Patient self-administers in some cases, which may reduce adherence or accuracy.

• IV ketamine:

  • Infusion rate and dose can be adjusted in real time based on patient response.

  • Monitored by an anesthesiologist or trained provider for safety and precision.

Why it matters: Real-time dosing control makes IV ketamine better suited for complex, high-risk, or highly sensitive cases.

4. Safety and Monitoring

• Intranasal ketamine:

  • Often given in a clinic but can be taken at home (in compounded form) without continuous monitoring.

  • Side effects include dizziness, dissociation, and increased blood pressure—generally mild but must be monitored in at-risk patients.

• IV ketamine:

  • Always given in a controlled medical setting with continuous monitoring of heart rate, blood pressure, and oxygen saturation.

  • Immediate medical intervention available if adverse effects occur.

Why it matters: Patients with cardiovascular risk factors or unstable mental states may require the additional safety of monitored IV administration.

5. Patient Suitability

• Intranasal ketamine may be a good option for:

  • Patients with mild to moderate depression who prefer a less invasive method

  • Those who respond well to ketamine but need at-home maintenance dosing

  • Patients who are needle-averse but otherwise medically stable

• IV ketamine may be a better choice for:

  • Severe treatment-resistant depression or PTSD

  • Urgent cases with suicidal ideation

  • Patients who have not responded to intranasal or oral ketamine

  • Complex medical histories requiring close supervision

6. Cost and Accessibility

• Intranasal ketamine:

  • Esketamine nasal spray (Spravato®) is FDA-approved and may be covered by insurance for depression.

  • Compounded ketamine sprays are usually less expensive but not covered by most plans.

• IV ketamine:

  • Usually an out-of-pocket expense, though some patients can use HSA/FSA funds.

  • Costs more per session but may require fewer treatments due to potency.

The Therapist’s Role in Choosing the Right Option

As a therapist, you’re often the one who knows your patient’s emotional, functional, and safety needs most intimately. Your guidance can help determine whether intranasal ketamine offers a sufficient therapeutic benefit—or whether it’s time to step up to IV ketamine therapy for maximum potency and consistency.

In many cases, the two are complementary, not competing. A patient might begin with IV ketamine to achieve rapid remission, then transition to intranasal ketamine for maintenance.

Bottom Line:

• Intranasal ketamine is accessible, less invasive, and effective for some patients—but has lower and less predictable bioavailability.

• IV ketamine therapy offers maximum absorption, precision dosing, and the fastest onset—making it the go-to for severe, urgent, or treatment-resistant cases.