Spravato vs. IV Ketamine: Understanding the Differences in Treatment Strength

Ketamine-based therapies have become leading options for individuals with treatment-resistant depression. Two forms are commonly used in clinical practice: Spravato (esketamine nasal spray) and IV ketamine infusions. While both treatments originate from the same medication family, their potency, delivery method, monitoring requirements, and therapeutic effects differ in important ways.

Understanding these differences helps patients choose the right treatment option based on safety, severity of symptoms, and clinical goals.

What Is Spravato?

Spravato (esketamine) is an FDA-approved nasal spray used for:

• Treatment-resistant depression

• Major depression with acute suicidal thoughts

• Adjunctive therapy alongside an oral antidepressant

Key features:

• Administered intranasally in a clinic

• Fixed dosing (56 mg or 84 mg)

• Requires 2 hours of post-administration monitoring

• Covered by many insurance plans

Spravato uses esketamine, the S-enantiomer of ketamine, which is more potent at key receptor sites.

What Is IV Ketamine?

IV ketamine is an off-label but widely used form of ketamine therapy delivered through intravenous infusion. It is commonly used for:

• Treatment-resistant depression

• Bipolar depression

• PTSD

• Severe anxiety syndromes

Key features:

• Customized dosing by weight (typically 0.5 mg/kg to 1 mg/kg)

• Greater bioavailability

• Rapid onset of effect

• Often used for patients with severe or prolonged symptoms

IV ketamine reaches 100% systemic availability.

Key Differences Between Spravato and IV Ketamine

1. Potency and Bioavailability

• IV Ketamine:
  Delivers the highest and most predictable bioavailability (100%). This makes it the stronger and more direct option, typically leading to rapid symptom relief.

• Spravato:
  Intranasal delivery yields an estimated 45–50% bioavailability. Although potent, it is less intense than IV ketamine.

2. Onset of Action

• IV Ketamine:
  Many patients feel improvement within hours or by the next day.

• Spravato:
  Effects typically build over multiple sessions, becoming noticeable within 2–4 weeks.

3. FDA Approval and Insurance

• Spravato:
  FDA-approved; frequently covered by insurance with prior authorization.

• IV Ketamine:
  Off-label; typically self-pay, though growing in acceptance.

4. Dosing Precision

• IV Ketamine:
  Highly customizable by weight, allowing titration for complex cases.

• Spravato:
  Limited to fixed doses (56 mg or 84 mg).

5. Duration of Sessions

• IV Ketamine: 40–60 minutes infusion + short monitoring

• Spravato: 2 hours of monitoring due to dissociative effects and blood pressure changes

6. Experience During Treatment

• IV Ketamine:
  Dissociation is often more pronounced due to higher systemic exposure. Many patients report a deeper “ketamine journey.”

• Spravato:
  Milder perceptual effects, sometimes described as “floating” or light dissociation.

Which Treatment Is Stronger?

Clinically speaking:

IV Ketamine is stronger, faster-acting, and more bioavailable.

It is often preferred for:

• Severe depression

• Rapid symptom relief

• Patients who have failed multiple medications

• Those needing flexible dosing

Spravato is structured, FDA-approved, and insurance-supported.

It is often preferred for:

• Patients needing close monitoring

• Those who respond well to fixed dosing

• Individuals seeking an FDA-approved treatment pathway

• Patients who prefer a gentler treatment experience

Both are effective, but they serve different roles in treatment planning.

Who Is a Candidate for Each Treatment?

Spravato may be ideal for:

• Individuals with treatment-resistant depression

• Patients who prefer an FDA-approved option

• Those needing structured monitoring

• Patients currently on antidepressants

IV Ketamine may be ideal for:

• Severe or long-standing depression

• Bipolar depression

• Suicidal ideation requiring rapid relief

• Patients who have not responded to Spravato

• Individuals comfortable with self-pay treatment

Safety and Monitoring Considerations

Both treatments require:

• Blood pressure monitoring

• Assessment before discharge

• Avoiding driving until the next day

• Use within a controlled clinical environment

Spravato requires REMS certification, while IV ketamine does not, but both demand experienced clinical oversight.

The Takeaway

Spravato and IV ketamine are powerful options for treatment-resistant depression, each with unique strengths. Spravato offers structure, approval, and accessibility, while IV ketamine delivers higher potency and rapid relief. Choosing the right treatment depends on clinical history, symptom severity, and personal preference.

Both can be life-changing when integrated into a comprehensive mental health care plan.