Ketamine Therapy for Depression

Ketamine therapy is the medical use of ketamine — a medication originally developed as an anesthetic — to treat severe, treatment-resistant depression and certain other mood conditions. It works through a different mechanism than traditional antidepressants (NMDA-receptor modulation rather than serotonin or norepinephrine), which is why it can help patients who haven't responded to SSRIs, SNRIs, or other standard medications.

Two forms are used in clinical settings:

• Spravato (esketamine) nasal spray — FDA-approved for treatment-resistant depression and for depression with active suicidal ideation. Administered in a certified clinical setting with a two-hour monitoring period after each dose.
• IV ketamine — a low-dose infusion given in a monitored clinical setting. Used off-label for treatment-resistant depression with strong supporting evidence.

Response can be rapid — within hours to days, rather than the weeks an SSRI takes. That's part of why it's particularly useful for patients in severe depressive episodes or with active suicidal thoughts.

Ketamine therapy is for adults with treatment-resistant depression — major depression that hasn't responded to two or more well-dosed antidepressant trials. The clearest candidates include patients who:

• Have tried multiple antidepressants without enough relief
• Are in a severe depressive episode and need faster relief than an SSRI can provide
• Have active suicidal ideation alongside major depression (Spravato has specific FDA labeling for this)
• Want a different mechanism than serotonin-targeted medications after years of partial response

Before considering ketamine, most patients work through standard depression treatment and often TMS therapy first. Ketamine isn't a first-line option, and it isn't appropriate for everyone — patients with uncontrolled high blood pressure, certain cardiovascular conditions, active psychosis, or active substance use disorders may need other paths. The SAMHSA mental health treatment locator and National Institute of Mental Health depression resource provide additional background on where novel treatments fit.

Ketamine therapy is not a take-home medication. Every dose is administered in a monitored clinical setting, with vitals checked before, during, and after. Here's the typical structure:

1. Evaluation visit — confirm the depression diagnosis, review medication history, screen for contraindications (cardiovascular, psychiatric, substance use), and decide whether IV ketamine or Spravato fits best.
2. Induction phase — Spravato is typically given twice weekly for the first 4 weeks. IV ketamine protocols vary but often involve 6 infusions over 2 to 3 weeks.
3. Each session — about 40 minutes of treatment (Spravato administration or IV infusion) followed by a 2-hour monitoring period. You'll feel the medication's effects during this window — mild dissociation, altered perception of time, and drowsiness are common.
4. No driving the day of treatment — you'll need a ride home. Plan the rest of the day around rest.
5. Maintenance phase — once weekly, then biweekly or monthly depending on response. We taper as your stability allows.

Set expectations honestly: ketamine works for many people, but not all. Initial response data suggests roughly 50–70% of treatment-resistant depression patients see meaningful benefit, with about half of those reaching remission.

Both options work; the choice depends on insurance, severity, and patient preference. Spravato (esketamine) — FDA-approved, which means it's the version most insurance plans actually cover. Administered as a nasal spray. Requires REMS-certified clinical setting and the 2-hour monitoring period. Best for patients whose insurance covers it after documented antidepressant failures. IV ketamine — typically used off-label for depression, so usually out-of-pocket. Some patients prefer the controllability of IV dosing or have responded to it specifically in the past.

We handle the prior authorization paperwork for Spravato — including the medication history documentation insurance requires — and we're transparent about cost expectations for IV ketamine before you start.

If ketamine isn't the right fit, we also discuss TMS therapy, which is non-invasive, drug-free, and broadly covered by Medicare and commercial insurance for treatment-resistant depression.

Talk to us about ketamine therapy if any of these are true:

• You've tried two or more well-dosed antidepressants without enough relief
• You're in a severe depressive episode and need faster relief than an SSRI can provide
• You're experiencing suicidal thoughts alongside major depression (Spravato has specific FDA approval for this combination)
• You've completed a TMS course and need another option
• You want to discuss whether IV ketamine or Spravato fits your situation better

If you're in immediate crisis, call or text 988 or go to your nearest emergency department. Ketamine is not an emergency intervention, but it can be the right next step once you're stable.

Ketamine therapy is too significant a treatment to be delivered in a vacuum. It works best when the team handling it knows your full medical picture and your other treatments are coordinated under the same roof.

• 22 years of clinical experience under our practice lead, including emergency department work where treatment-resistant depression presents in its most urgent forms
• Primary care plus mental health under one roof — cardiovascular screening, blood pressure management, and medication reconciliation happen in the same place
• Hands-on insurance authorization for Spravato — we own the paperwork
• Clinical-setting administration with monitoring — vitals, observation, and the full 2-hour post-dose window
• Honest expectations — we'll tell you what the evidence shows for your specific situation, including when ketamine isn't the right fit
• Serving the Triangle — Knightdale, Wendell, Zebulon, Rolesville, Wake Forest, Garner, and East Raleigh

If standard treatments haven't worked, ketamine therapy may give you a real next step. Let's talk about whether it's the right one for you.