What 'treatment-resistant' means
"Treatment-resistant depression" (TRD) is a clinical term used when a person has not experienced adequate relief after trying two or more evidence-based antidepressants at adequate doses for adequate durations. It does not mean the person did something wrong; it reflects the limits of any single treatment approach. TRD is common: research suggests that about one-third of people with major depressive disorder do not respond well to first-line treatments.
Why ketamine drew clinical interest
Two features made ketamine notable in depression research: onset and mechanism. Some studies reported meaningful improvements in mood within hours to days of a single low-dose session — dramatically faster than the four to eight weeks typically required by SSRIs. Its mechanism (NMDA receptor modulation and downstream neuroplasticity) is also different from traditional antidepressants, offering a potentially useful option for patients who have not responded to the standard pathways.
What the evidence supports
Rapid, short-term reduction in symptoms
Multiple studies have observed rapid antidepressant effects from single sub-anesthetic doses of ketamine. Effects for a single dose typically fade within days to a couple of weeks, which is why repeat dosing protocols exist.
Repeated dosing plus integration for durability
More durable improvement typically requires a series of sessions — often described as an induction phase — followed by clinical judgment about maintenance. Combining ketamine sessions with psychotherapy and structured integration tends to be associated with better outcomes than medication alone.
Esketamine (Spravato)
Esketamine, the S-enantiomer of ketamine, is FDA-approved as an intranasal spray for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is delivered under supervision in a certified in-office setting under the FDA's REMS program. Our program uses low-dose oral ketamine — a different modality, prescribed off-label.
Where the evidence is still developing
The research is active. Areas where evidence is still maturing include long-term outcomes over years, optimal maintenance schedules, ideal dosing for specific depression subtypes, and how ketamine best combines with specific psychotherapy modalities. A responsible clinical program is transparent about these open questions rather than overselling.
Who might be an appropriate candidate
Ketamine therapy is generally considered for adults with persistent depression who have not experienced adequate relief from standard treatments. It is not appropriate for everyone. Considerations that typically weigh against candidacy include uncontrolled cardiovascular disease, active psychosis or mania, certain substance use disorders, active pregnancy, and specific medication interactions.
Ketamine is not intended to replace psychotherapy or existing psychiatric medications. Any changes to other medications should always happen under the supervision of the prescribing provider.
What realistic expectations look like
A helpful mental frame: ketamine may help open a window during which change is more possible; the work you do inside that window — through therapy, integration, and daily habits — is what tends to make change last. Some patients experience meaningful shifts early on; others take longer; some do not respond adequately. Individual results vary. The clinical goal is a considered, honest assessment of your response, not persistence with a plan that is not helping.
Bottom line
Ketamine is one option among several for people with hard-to-treat depression. Whether it is right for you is a clinical determination that requires a comprehensive medical evaluation. The best next step is a free, no-obligation discovery call — we can answer your questions and explain what an evaluation would involve.