What Counts as Treatment-Resistant Depression for Spravato Approval?

“Treatment-resistant depression” sounds like a technical diagnosis, but for most patients, it’s a label they encounter only after years of trying different medications with limited success.

If you’re exploring Spravato, understanding what clinicians and insurers mean by treatment-resistant depression (TRD) can make the process feel far less opaque.

In most clinical and insurance settings, treatment-resistant depression means:

• You’ve been diagnosed with major depressive disorder
• You’ve tried at least two different antidepressant medications
• Those medications were taken at appropriate doses and durations
• Your symptoms did not improve enough, or the medications were not tolerable

This definition isn’t about blame or severity. Many people with TRD are highly functional on the outside while continuing to struggle internally.

One of the biggest questions patients have is whether their past treatments “count.”

Generally, an antidepressant trial is considered adequate if:

• It was prescribed by a licensed medical provider
• It was taken consistently
• It was continued long enough to reasonably assess effectiveness

If a medication was stopped early because of side effects, that often still counts. In fact, medication intolerance is a common reason patients move toward alternative treatments like Spravato.

During a Spravato evaluation, providers typically review your full medication history, not just the most recent prescriptions.

Treatment-resistant depression doesn’t always mean trying medications one at a time.

Many patients qualify for TRD after:

• Using antidepressant combinations
• Adding mood stabilizers or antipsychotic medications
• Adjusting doses multiple times without meaningful relief

These attempts demonstrate that standard treatment pathways were pursued — even if none provided lasting benefit.

A common misconception is that TRD only applies to people with the most extreme symptoms.

In reality, TRD is defined by response to treatment , not by how depression looks on paper. Someone with moderate but persistent symptoms may meet criteria just as clearly as someone with more severe depression.

What matters most is whether traditional treatments have failed to provide adequate relief.

Insurance approval for Spravato often depends on documentation, but patients don’t need to have everything figured out in advance.

During an evaluation, providers help:

• Review medication history
• Identify qualifying treatment attempts
• Coordinate with past or current prescribers when needed

Many patients assume they don’t qualify because their history feels “messy.” In reality, incomplete or fragmented care histories are common — and navigable.

Hearing the term “treatment-resistant” can feel discouraging, but it’s not a dead end.

Spravato was developed specifically for people whose depression hasn’t responded to conventional medications. Its mechanism of action is different, which is why it can be effective even when multiple antidepressants haven’t worked.

For many patients, TRD isn’t a label of hopelessness — it’s the reason Spravato becomes an option.

Spravato is typically used alongside ongoing psychiatric care, not as a standalone solution.

A thoughtful treatment plan looks at:

• Past medication response
• Current symptoms
• Safety considerations
• Long-term support and follow-up

This approach helps ensure Spravato is used appropriately and effectively, rather than as a last-ditch effort.

If you’re unsure whether your history meets the definition of treatment-resistant depression, the best next step is a clinical evaluation that looks at the full picture — not just a checklist.

You can learn more about Spravato treatment and how eligibility is evaluated at Therapeutic Infusions on our Spravato treatment page.