Ketamine for Depression

What is ketamine?

Ketamine is a dissociative anesthetic that has been used in medical settings since 1970 — originally for surgical anesthesia and emergency pain control. In the past two decades, researchers discovered that at much lower doses than used for anesthesia, ketamine has powerful and rapid antidepressant effects.

That's what's meant when people say "ketamine for depression." We're not putting patients under for surgery. We're giving a carefully measured, monitored, sub-anesthetic dose that engages the brain's mood circuits differently than any other antidepressant medication.

How does it work?

Most antidepressant medications (SSRIs, SNRIs, etc.) work on the brain's serotonin, norepinephrine, or dopamine systems. Ketamine works very differently. It acts on a receptor system called NMDA (N-methyl-D-aspartate) and another called AMPA, both of which are part of the brain's glutamate signaling system — a different neurotransmitter pathway entirely.

Without going into heavy neuroscience, what's thought to happen is something like this: ketamine briefly changes the way certain neurons communicate, which triggers a cascade of downstream effects — including the release of growth factors (like BDNF) and increased formation of new synaptic connections between brain cells. This is sometimes described as increased neuroplasticity, and it's thought to be the underlying reason for the antidepressant effect.

The important takeaway for patients: ketamine works through a completely different mechanism than standard antidepressants, which is part of why it can help people who haven't responded to other medications.

Is ketamine right for me?

Ketamine is most commonly considered for:

• Treatment-resistant depression — major depression that hasn't responded adequately to two or more antidepressant trials
• Severe depression with suicidality — where rapid effect is clinically valuable
• Bipolar depression (in carefully selected cases)
• PTSD (emerging use; less robust evidence than for depression)

When ketamine isn't the right fit

Some patients shouldn't get ketamine because of medical or psychiatric factors. Key ones include:

These aren't always absolute — some can be worked around with careful screening and planning. The point of a thorough psychiatric and medical evaluation before starting is to figure out whether ketamine makes sense for you specifically.

What a treatment is like

The details depend on which form of ketamine you're receiving (IV, nasal spray, oral). For an IV ketamine infusion — the most common form — here's roughly what to expect:

1. Arrival and setup (10–15 minutes): You'll settle into a comfortable reclining chair. A nurse or technician will check your vital signs and place an IV line. You'll be connected to monitors: a blood pressure cuff, a pulse oximeter (measures heart rate and oxygen), and often an EKG (measures heart activity).
2. Infusion (40–60 minutes): The ketamine is delivered slowly through your IV. Most patients feel the effects begin within a few minutes. The dose is carefully measured to your body weight.
3. Recovery (30–60 minutes): After the infusion ends, the effects wear off over about 30–60 minutes. You'll remain monitored until you're fully clear-headed and able to safely leave. You cannot drive afterward and will need someone to pick you up.

What the experience feels like

Because ketamine is a dissociative anesthetic, most patients have some kind of altered-state experience during the infusion. This varies enormously from person to person:

• Some feel very heavy, grounded in their body; others feel like they're floating or flying
• Some feel euphoric; some feel anxious or scared; some feel nothing at all notable
• Some people hallucinate mildly; others don't
• Strange thoughts, feelings, memories, or emotional material may surface during the session — sometimes pleasant, sometimes difficult

The different forms of ketamine

Ketamine can be delivered in several ways, each with its own tradeoffs:

IV ketamine (intravenous)

The most studied form. Delivered through an IV over 40–60 minutes, 100% of the dose reaches your bloodstream, dosed by body weight. Typically given in a clinic under direct physician supervision. Not usually covered by insurance.

Spravato (esketamine nasal spray)

The only form of ketamine that is FDA-approved for depression, approved in 2019 for treatment-resistant depression and depression with suicidal ideation. Given as a nasal spray in a certified clinic; you stay for ~2 hours of monitoring after each dose. Typically covered by insurance.

Oral ketamine

Can be taken at home by prescription. Cheaper and more convenient, but only about 20–30% of the dose is absorbed, and evidence for oral ketamine in depression is less robust than for IV or nasal forms. Requires careful prescribing because of higher potential for misuse.

Intramuscular (IM) ketamine

Delivered as an injection into muscle. Less common in clinical practice, but an option in some settings. Good bioavailability (~93%) but less precise dose control than IV.

Preparing for treatment

The day of your infusion

• Nothing to eat or drink for 8 hours before (though some clinics allow clear liquids up to 3 hours before — follow your specific provider's instructions)
• Arrange a ride home. You cannot drive yourself after the infusion
• Bring comfortable clothes. You'll be reclining for an hour or more
• Bring headphones and music if your clinic allows it — music can shape the experience significantly
• Avoid heavy caffeine or stimulants beforehand

Medications that can interfere

Certain medications can reduce ketamine's effectiveness. Talk to your prescriber before your first infusion about whether you need to adjust any of these:

• Benzodiazepines (Valium, Klonopin, Ativan, Xanax) — can blunt the antidepressant effect
• Lamotrigine (Lamictal) — can interfere with mechanism of action
• Naltrexone — can block the opioid-receptor component of ketamine's effect

Do not stop any medication without talking to your prescriber first.

Mindset and setting (the psychology of preparation)

There's a concept borrowed from the psychedelic literature called "set and setting" — the idea that your mental state going in (set) and your physical surroundings (setting) shape the experience you have. Ketamine isn't the same as a classical psychedelic, but the principle applies.

Setting includes the room, the lighting, the chair, what you're wearing, whether you have music, the people around you. Most of this is handled by the clinic, but you can influence pieces of it.

Mindset is more about what you bring: your expectations, intentions, self-awareness, and attitude. Thinking about questions like how do I interface with discomfort? How do I self-soothe? What do I do if difficult feelings come up? beforehand tends to make the experience itself go more smoothly.

Side effects and safety

Ketamine is generally safe when given in a medical setting with proper monitoring. That said, every effective treatment has side effects, and ketamine has some specific ones worth knowing.

Common side effects (during and shortly after treatment)

• Feeling intoxicated or "out of body" (dissociation)
• Elevated blood pressure and heart rate
• Anxiety, especially during the infusion
• Blurred vision, dizziness
• Nausea
• Headache

These effects typically resolve within 30–60 minutes after the infusion ends.

Less common but important risks

Will it keep working?

This is one of the most important things to understand about ketamine: it's not a one-and-done cure. For most patients, a single treatment's benefit fades within days to weeks. To get sustained relief, ketamine is usually given as a course:

• Initial series: Typically 6 treatments over 2–3 weeks (usually 2–3 per week)
• Taper: After the initial series, treatments are spaced out gradually — weekly, then every 2 weeks, then monthly as tolerated
• Maintenance: Some patients continue at every 2–4 weeks indefinitely; others are able to stop entirely after a successful initial course

Evidence suggests that combining ketamine with psychotherapy — particularly CBT or behavioral activation — can help the benefits last longer. Ketamine works better as part of an overall treatment plan (including therapy, medication, exercise, sleep, and social support) than as a standalone intervention.

Common questions

How does ketamine compare to ECT?

ECT is generally the most effective treatment we have for severe depression. Ketamine works nearly as fast as ECT in some patients, and for many it's a less intensive option — no anesthesia for the treatment itself, no cognitive side effects like memory issues, shorter sessions. The best choice depends on severity, urgency, prior treatments, and personal factors. Neither is universally better.

Is ketamine the same as a "ketamine clinic" or street ketamine?

"Ketamine clinics" vary in quality and clinical rigor. Some are excellent, closely integrated with psychiatric care. Others provide infusions without adequate screening, monitoring, or follow-up. The quality of the program matters. Street ketamine is different — uncontrolled dose, often contaminated, no medical supervision, and with much higher risks.

Will I be myself during the treatment?

You'll be awake and aware, but the experience feels altered. You can usually speak, respond to staff, and signal if something is wrong. You won't be unconscious. The dissociation is part of the treatment, not a sign of something going wrong.

How will I know if it's working?

Most patients who respond notice meaningful improvement within 1–3 treatments — sometimes within hours of the first infusion. We'll track symptoms formally across the course. If after the initial series there's no meaningful benefit, we re-evaluate.

Can ketamine treat things other than depression?

There's emerging evidence for PTSD, bipolar depression, and some types of chronic pain. The strongest evidence remains in depression. Treatment for non-depression indications is often considered off-label and should be approached with realistic expectations.

Helpful resources

Get in touch

If ketamine might be a fit for you, or if you're considering treatment and want to talk through your options, the Prisma Health Neuromodulation Program provides consultations and ketamine treatment.