Ketamine for Treatment-Resistant Depression (TRD)

Treatment-resistant depression — TRD — is not a personal failure and not a dead end. It is a clinical term for depression that has not responded adequately to standard treatment. A commonly used definition in research describes TRD as inadequate response to two or more antidepressant trials of adequate dose and duration, though the exact definition varies between studies and clinicians.

If you have tried two, three, or more antidepressants without enough relief, you already know how heavy that history feels. What the label should do is open a different conversation about options — not close one.

When first-line treatments fall short, psychiatrists typically consider medication adjustments or combinations, structured psychotherapy, neuromodulation treatments such as ECT or TMS, and esketamine. Supervised ketamine therapy may also be considered. Each option carries its own evidence, burdens, and risks, and the right sequence is individual.

We never present ketamine as the obvious next step. It is one option among several, and part of our job is helping you weigh it honestly against the others — including options we do not provide.

Much of the ketamine research specifically involved people with treatment-resistant depression. In a 2013 randomized trial, Murrough and colleagues compared IV ketamine with an active comparator in adults with TRD and found greater short-term symptom reduction for some of those receiving ketamine. Earlier work, including the 2006 Zarate trial, pointed in the same direction.

The limits matter as much as the findings: follow-up in these studies was short, not everyone responded, and researchers are still working out how durable the benefit is and what maintenance should look like. IV ketamine is not FDA-approved for TRD; esketamine (Spravato) is FDA-approved for specific depression indications, including treatment-resistant depression in adults.

For TRD, the evaluation focuses on your treatment history: which medications you tried, at what doses, for how long, and what happened. Records from past prescribers help. So does a clear picture of your medical conditions and current medications, since some of these may rule ketamine out.

Bring your skepticism. If your history suggests something else should be tried first — or that ketamine is unlikely to be a good fit — we will say so plainly.

Side effects during sessions are usually short-lived — dissociation, nausea, dizziness, temporary blood-pressure changes — and are managed with monitoring. Longer-term questions, including whether and how often maintenance sessions may be useful for you, are answered individually and revisited as we go.

Depression this persistent can bring thoughts of self-harm. We ask about them directly during evaluation so care can be planned safely, without judgment.