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, TMS and many insured treatments, and each qualifier can sink an authorization. See the Spravato hub, the coverage hub, the candidate screener, treatment comparisons and condition and treatment pages.

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.

Documenting your history

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.

Current episode versus lifetime

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 it matters beyond paperwork

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.

Next steps

Use the candidate screener to check your history against the criteria, then read your plan's rules on the coverage hub.