How Spravato Works for Treatment-Resistant Depression

For the millions of people whose depression hasn't responded to traditional antidepressants, Spravato (esketamine) represents a breakthrough. This FDA-approved treatment works through a completely different mechanism than conventional medications, offering hope when other treatments have failed.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is diagnosed when someone has tried at least two different antidepressant medications at adequate doses for adequate duration without achieving remission. This affects approximately one-third of people with major depressive disorder.

Signs of Treatment-Resistant Depression

• Tried multiple antidepressants without adequate response
• Initial improvement that fades over time
• Depression continues to significantly impair daily functioning
• Persistent hopelessness despite treatment efforts

What Is Spravato?

Spravato is the brand name for esketamine, a nasal spray approved by the FDA in 2019 for treatment-resistant depression and in 2020 for major depressive disorder with suicidal ideation. It's derived from ketamine, an anesthetic that has been used safely in medical settings for decades.

Key Facts About Spravato

Administration: Nasal spray given in a certified healthcare setting
Frequency: Initially twice weekly, then weekly, then weekly or bi-weekly
Used with: An oral antidepressant (not as standalone treatment)
Monitoring: Requires 2-hour observation after each treatment

How Spravato Works: The Science

Traditional antidepressants work by increasing levels of serotonin, norepinephrine, or dopamine. Spravato works through an entirely different mechanism:

NMDA Receptor Modulation

Spravato blocks NMDA receptors, which affects glutamate signaling—the brain's primary excitatory neurotransmitter

Rapid Synaptogenesis

Triggers growth of new synaptic connections, essentially helping the brain rewire itself

BDNF Release

Increases brain-derived neurotrophic factor, a protein that supports brain cell health and growth

Fast Action

Because of this mechanism, effects can be felt within hours to days, not weeks like traditional antidepressants

Think of depression as having weakened neural pathways. Traditional antidepressants try to strengthen existing paths by adjusting chemical messengers. Spravato helps create new paths entirely—a faster route to relief.

What to Expect During Treatment

Before Your First Session

Complete evaluation to confirm you're a candidate
Don't eat for 2 hours before treatment (light snack okay)
Arrange transportation home (you cannot drive for 24 hours)
Bring comfortable clothing and any items that help you relax

During the Session

1. Baseline vitals: Blood pressure checked before treatment
2. Self-administration: You spray the medication under supervision
3. Relaxation: Rest in a comfortable setting for 2 hours
4. Monitoring: Staff checks on you periodically; vitals monitored
5. Post-assessment: Final vitals and assessment before discharge

Common Experiences During Treatment

Many people experience transient effects that typically resolve within 1.5 hours:

Dissociation (feeling disconnected from yourself or surroundings)
Dizziness or light-headedness
Nausea
Increased blood pressure (temporary)
Altered perception (time, colors, sounds)
Drowsiness

These effects are expected and monitored. Most people describe the experience as unusual but not unpleasant, often comparing it to a dreamlike state.

Treatment Schedule

Typical Protocol

Weeks 1-4: Twice weekly sessions
Weeks 5-8: Weekly sessions
Week 9 onward: Weekly or every two weeks (individualized)

Your provider will adjust the schedule based on your response. Some people eventually extend to less frequent maintenance sessions.

Who May Benefit from Spravato?

Good Candidates

• Adults with treatment-resistant depression (failed 2+ antidepressants)
• Those with major depression and acute suicidal ideation
• People seeking faster relief than traditional medications provide
• Those who can commit to the treatment schedule

Spravato May Not Be Right For

• People with uncontrolled hypertension
• Those with certain vascular conditions (aneurysms, hemorrhagic stroke history)
• People with active substance use disorders involving ketamine or PCP
• Those who cannot arrange transportation after sessions

Effectiveness and Research

Clinical trials have shown significant benefits:

In studies, Spravato plus oral antidepressant showed greater improvement than oral antidepressant alone
Some patients experience improvement within hours to days of first treatment
Long-term studies show sustained benefit with maintenance treatment
Particularly effective for depression with suicidal ideation

Results vary by individual. Some people respond dramatically; others see modest improvement. Your provider will assess response and adjust treatment accordingly.

Frequently Asked Questions

"Is Spravato the same as ketamine?"

Spravato is esketamine, a more potent form of one component of ketamine. It's FDA-approved with standardized dosing and safety protocols.

"Is it addictive?"

While ketamine can be misused, Spravato is administered only in certified healthcare settings with strict controls. Risk of addiction is low in this supervised context.

"Does insurance cover it?"

Many insurance plans cover Spravato, though prior authorization is typically required. Our team can help verify your coverage.

"How long do I need treatment?"

Duration varies. Some continue maintenance indefinitely; others eventually taper. This is determined based on your response and needs.

Taking the Next Step

If you've struggled with depression despite trying multiple treatments, Spravato may offer new hope. The first step is a comprehensive evaluation to determine if you're a candidate and to develop a personalized treatment plan.