Ketamine Therapy Comparisons

SSRIs are the first-line antidepressant for most people. Ketamine is typically considered after SSRIs and other options have not produced adequate response, or in specific clinical contexts.

Esketamine is the S-enantiomer of ketamine, delivered intranasally and FDA-approved for treatment-resistant depression. Racemic ketamine is the mixture used off-label in most clinics.

TMS (transcranial magnetic stimulation) is a non-invasive, non-medication option for depression. Ketamine is a pharmacological option with rapid effects.

Psilocybin is an investigational psychedelic with active depression research. Ketamine is legally available in clinical settings; psilocybin is not, outside research and limited regulated programs.

MDMA-assisted therapy is investigational and primarily studied for PTSD. Ketamine is clinically available and used for depression, with growing PTSD research.

Therapy and ketamine are usually complementary, not competing. Most clinicians consider ketamine most useful when paired with ongoing therapeutic work.

ECT remains the most effective treatment for severe, treatment-resistant depression. Ketamine is faster to access, less invasive, and easier to repeat — but does not match ECT's response rate in the most severe cases.

MAOIs are powerful older antidepressants effective for atypical and treatment-resistant depression. They require strict dietary and drug interaction discipline. Ketamine offers comparable response without dietary restrictions.

Microdosing psilocybin or LSD has grown popular but lacks robust controlled evidence. Therapeutic ketamine operates at meaningfully different doses, in clinical settings, with stronger short-term data.

Lithium augmentation has decades of evidence in treatment-resistant depression. Ketamine offers faster relief but less long-term outcome data. They are sometimes used together.

Auvelity is an FDA-approved oral antidepressant that also acts on NMDA receptors. It offers a take-home alternative to ketamine but with smaller effect sizes in published trials.

Sleep, exercise, nutrition, sunlight, and social connection have measurable antidepressant effects. They are foundational, not optional — and ketamine works substantially better in patients with these foundations in place.

Both target the glutamate system for treatment-resistant depression, but they differ in molecule, route, FDA status, insurance coverage, and clinical evidence base. This guide compares them across the decisions patients actually face.