Ketamine Nasal Spray: What Patients Need to Know

Introduction

Ketamine nasal spray (specifically its derivative esketamine) is an FDA-approved treatment for treatment-resistant depression (TRD). It offers a faster onset of relief compared to standard antidepressants and is administered in a clinical setting under supervision. However, it comes with risks and safety requirements that patients should understand fully before pursuing this therapy.

‍

How It Works

Esketamine is a more potent version of ketamine that acts on the glutamate system rather than serotonin or dopamine. Because of this difference in mechanism, it can promote synaptic plasticity and restore neural connections more quickly than traditional antidepressants.

In clinical settings, doses are delivered via a nasal spray device (Spravato® label, FDA) - typically 28 mg per device - and often administered in two to three sprays per session, followed by observation to monitor side effects.

‍

Who Is a Candidate?

Esketamine nasal spray is indicated for adults with TRD — meaning they’ve tried at least two antidepressants of adequate dose and duration without remission. It’s also used for major depressive disorder with suicidal ideation or behavior under careful supervision.

Because of risk factors, not everyone qualifies. Patients with uncontrolled hypertension, aneurysms, intracranial hemorrhage risk, or hypersensitivity to esketamine are contraindicated (FDA label).

‍

Treatment Schedule & Duration

• Induction phase (first 4 weeks): typically twice weekly dosing.
• Maintenance phase: frequency is reduced—weekly, biweekly, or monthly, depending on response (long-term study, PMC).
• In studies combining TRD + PTSD, intranasal esketamine showed significant improvement over six months, with many patients responding or reaching remission (pilot study, PMC).

‍

Efficacy: What the Research Shows

• In a pilot study of TRD + PTSD patients, mean depression scores dropped from 38.6 to 18.2 after six months; ~63% responded, ~27% achieved remission (PMC9305073).
• Systematic reviews confirm that intranasal ketamine/esketamine offers rapid antidepressant action and can reduce suicidality risk in TRD and MDD.
• Long-term data is still emerging, but studies from Harvard Health show nasal ketamine (adjunct to antidepressants) helps maintain remission for 16 weeks or more.

‍

Risks & Side Effects

• Common side effects include dissociation, sedation, dizziness, nausea, increased blood pressure, and perceptual disturbances (FDA label).
• Because of these effects, patients remain in the clinic for at least 2 hours post-dose for monitoring.
• The FDA warns about compounded ketamine nasal sprays due to unregulated dosing and safety concerns.
• Note: ketamine (for psychiatric treatment) is not FDA-approved; only esketamine (Spravato) is approved for TRD/MDD (FDA communication).

‍

Costs, Insurance & Accessibility

Esketamine (Spravato) is administered under the FDA’s REMS program and only at certified clinics (Mayo Clinic).

Coverage varies by insurer, and out-of-pocket costs can be significant - something clinics should discuss clearly with patients.

‍

FAQs

Q: Is esketamine nasal spray a one-time cure?

A: No. It’s typically a maintenance therapy, with dosing intervals relaxed as symptoms improve.

‍

Q: How quickly does it work?

A: Many patients feel relief within hours or days of initial treatment (Hopkins Medicine).

‍

Q: Can I self-administer at home?

A: No. Due to sedation and dissociation risks, esketamine must be given in a monitored clinical setting.

‍

Q: What about compounded ketamine nasal sprays?

A: They pose significant risks; the FDA warns against using compounded ketamine for psychiatric disorders (FDA Alert).

‍

Q: Will I need to take an oral antidepressant too?

A: Often yes, though recent FDA guidance allows esketamine as monotherapy for some cases.

‍