Treatment-resistant depression: what the criteria actually mean

The working definition

Treatment-resistant depression (TRD) is major depressive disorder that has not responded adequately to at least two different antidepressants, each taken at an adequate dose for an adequate duration in the current episode. That phrase, with three qualifiers, is the gate to Spravato (esketamine), TMS (transcranial magnetic stimulation) and many insured treatments, and each qualifier can sink an authorization. The candidate screener lines a history up with those rules. Read Spravato coverage by insurer. For the session schedule and common questions in one place, see the Spravato overview.

What counts as adequate

Dose:

at or above the minimum effective dose in the label (for example, sertraline 50 mg, escitalopram 10 mg, venlafaxine 75 mg, bupropion 300 mg).

Duration:

at least six weeks at that dose. Some plans accept four; some require eight.

Different agents:

two different medications. Many plans also want them from different classes, or at least one augmentation strategy.

Adequate response:

less than 50 percent improvement on a rating scale, or persistent symptoms in the clinician's judgment.

Stopping a drug at week two for side effects is intolerance, not failure. Most plans count intolerance toward the trial requirement, but it must be documented as such.

How do I document antidepressant trials?

The prior authorization lives or dies on a medication list with dates and doses. Assemble it before your intake:

1. Ask your pharmacy for a dispensing history for the past five years.
2. Note the start and stop dates and the highest dose for each antidepressant.
3. Note why each one stopped: no effect, partial effect, or side effects.
4. Bring past rating scale scores if you have them; a baseline PHQ-9 at the intake is the minimum.

Do past antidepressants count?

Most policies require the failed trials to be in the current episode. If you responded to a medication years ago, recovered, and relapsed, the clock restarts. Clinicians can often document continuity of the episode when treatment gaps were short.

Why do failed antidepressant trials matter?

The STAR*D trial showed each successive medication trial has a lower chance of remission. After two failed trials, the odds of a third medication working fall below 15 percent, which is the clinical argument for moving to interventional treatments rather than a fourth pill. Insurers built their criteria on that evidence.

What should you do after checking the criteria?

Use the candidate screener to check your history against the criteria, then read your plan's rules on the coverage hub. When your history meets the criteria, How do I get Spravato approved by my insurance? covers the prior authorization request, and Spravato vs TMS: how to choose compares the two treatments that definition opens.

Read Spravato for treatment-resistant depression, TMS for treatment-resistant depression and Ketamine therapy for treatment-resistant depression.

Related reading: how these criteria apply to each treatment is covered in Spravato: the complete guide and TMS: the complete guide.