Ketamine Treatment for Depression: Benefits, Risks and What to Expect

What is ketamine therapy for depression?

Ketamine is a different type of antidepressant treatment that can produce improvement substantially faster than conventional antidepressants in some people with difficult-to-treat depression. It does not help everyone, and repeated treatment may be required to establish or sustain benefit.

Originally used as an anaesthetic, ketamine is administered at different doses and in different settings when used for depression. It is generally considered after established options—such as psychotherapy, antidepressant medication or other appropriate treatments—have not provided enough benefit or have caused unacceptable adverse effects.

This article provides general education rather than individual medical advice. Whether ketamine or esketamine is appropriate depends on a psychiatric and medical assessment, previous treatments, current medications, health conditions, substance-use history and personal treatment goals.

What does treatment-resistant depression mean?

Treatment-resistant depression describes depression that has not improved sufficiently despite appropriate treatment attempts. Studies and guidelines do not always use exactly the same definition, although research commonly refers to inadequate benefit from two or more antidepressant trials.

A limited response does not mean a person is beyond help. It may prompt a careful review of the diagnosis, medication dose and duration, adherence, co-occurring conditions, psychotherapy, sleep, substance use and other factors before choosing the next treatment.

Ketamine is not generally a routine first treatment because conventional options have longer-established evidence, broader clinical experience and fewer monitoring demands. Ketamine also has short-term psychoactive and cardiovascular effects, potential for misuse, and unresolved questions about long-term treatment.

Ketamine versus esketamine: what is the difference?

Racemic ketamine contains two mirror-image forms of the molecule: R-ketamine and S-ketamine. Esketamine contains only the S form. They are related but are not interchangeable products, and evidence from one formulation or route should not automatically be assigned to another.

Routes also matter. Much of the randomized evidence for racemic ketamine in depression involves intravenous infusions. NeuroLinks does not provide intravenous ketamine; the clinic provides intramuscular racemic ketamine.

Intranasal esketamine is delivered as a nasal spray under clinical supervision. Its evidence base includes short-term trials and relapse-prevention studies that are separate from the racemic-ketamine literature.

How does ketamine work for depression?

Ketamine acts differently from conventional antidepressants that primarily influence serotonin, norepinephrine or dopamine. It affects glutamate signalling, including N-methyl-D-aspartate—or NMDA—receptors, and appears to influence downstream AMPA-receptor activity and pathways involved in synaptic plasticity.

Synaptic plasticity refers to the brain’s capacity to adjust connections and communication between nerve cells. Ketamine may also affect brain-derived neurotrophic factor and related signalling. These mechanisms remain under investigation, and no brain scan or laboratory test can currently predict with certainty who will benefit.

The temporary altered state that some people experience during treatment is not the same thing as antidepressant response. A person may experience dissociation without later improvement, while another may improve without a pronounced subjective experience.

How quickly does ketamine work for depression?

Rapid onset is one of ketamine’s distinctive characteristics. Some controlled intravenous studies have detected reductions in depressive symptoms within four hours or approximately one day. This is substantially faster than the several weeks conventional antidepressants may require.

A 2026 JAMA Psychiatry systematic review and meta-analysis combined 26 randomized trials involving 1,166 people with a major depressive episode. Compared with control conditions, intravenous racemic ketamine reduced depressive symptoms at four hours, 24 hours, three days and one week after a single infusion, as well as at the end of repeated-infusion treatment. The trials varied, and several analyses had substantial heterogeneity.

These results do not mean everyone feels dramatically better after one treatment. Improvement may be partial, may emerge over several sessions or may not occur. Evidence about rapid effects from intravenous trials also cannot be assumed to quantify the effect of intramuscular ketamine.

How effective is ketamine for depression?

Evidence supports a meaningful short-term antidepressant effect for intravenous racemic ketamine in some appropriately selected adults, particularly those with difficult-to-treat depression. The size and duration of benefit vary, and longer-term outcomes are less certain.

In the 2026 meta-analysis, a single intravenous ketamine infusion produced higher depression response rates than control at four hours, 24 hours, three days and one week. In these trials, response generally meant at least a 50% reduction on a depression rating scale. Pooled remission rates were not significantly different, and pooled response after repeated infusions was also not statistically significant, despite an overall reduction in symptom severity. These mixed outcomes show why one statistic should not be treated as a personal forecast.

A 2023 Lancet review summarized an earlier systematic review of seven placebo-controlled intravenous trials. It reported increased odds of response and remission around 24 hours, followed by declining effectiveness over the next week. The Lancet authors also cautioned that reviews of ketamine and esketamine had methodological limitations, including risk of bias and inconsistent assessment of study quality.

Esketamine has its own trial program. In the 28-day TRANSFORM-2 randomized trial, intranasal esketamine plus a newly initiated oral antidepressant reduced depression scores more than nasal placebo plus an oral antidepressant. Two related short-term trials produced similar numerical differences but did not meet statistical significance. In the SUSTAIN-1 relapse-prevention trial, people who had already responded or remitted were less likely to relapse when continuing esketamine with an oral antidepressant than when switching to placebo nasal spray.

Ketamine has also been compared with electroconvulsive therapy in selected patients with nonpsychotic treatment-resistant depression. One large trial found intravenous ketamine non-inferior to electroconvulsive therapy for its specified short-term outcome, but that does not establish universal equivalence. Electroconvulsive therapy remains a distinct treatment with different evidence, indications, risks and practical considerations.

What happens during treatment?

The exact process depends on the formulation and the clinic’s protocol. Treatment should begin with an assessment of psychiatric history, previous treatments, medications, physical health and factors that could increase risk. Baseline symptom measures may be used to track change over time.

During a supervised session, clinicians may monitor blood pressure, heart rate, symptoms and level of alertness. Intramuscular ketamine is administered by injection, whereas esketamine is administered intranasally. Observation after dosing allows temporary effects to settle and gives the clinical team an opportunity to assess safety.

Patients should expect transportation and post-treatment safety instructions because attention, coordination and judgment can be temporarily impaired. The treating clinic should provide individualized directions about eating, drinking, medications, driving, work and the need for an escort.

What does ketamine feel like?

Experiences vary. Some people describe relaxation, lightness, dream-like sensations, changes in time or space, emotional distance, visual changes or feeling disconnected from their body or surroundings. This disconnection is called dissociation.

Others may feel dizzy, sleepy, anxious, confused, nauseated or emotionally uncomfortable. These effects are usually temporary in controlled trials, but the experience is not universally pleasant. Patients remain under observation so that physical or psychological effects can be addressed.

Side effects and risks

In the supplied intravenous trials, common short-term effects included dissociation, dizziness, drowsiness, nausea, headache, blurred vision, altered sensations, anxiety, impaired coordination and temporary increases in blood pressure or heart rate. Most resolved within a few hours, but some participants stopped treatment or required additional observation.

A clinical assessment is needed because ketamine or esketamine may not be suitable for everyone. Particular attention may be required for cardiovascular conditions, a history of psychosis or mania, pregnancy, cognitive concerns, substance-use problems and medications that could interact with treatment. This is not a complete list of contraindications.

Ketamine has misuse and dependence potential. Concerns associated with frequent or high-dose non-medical use—including urinary tract, cognitive and other harms—cannot be equated directly with supervised psychiatric treatment, but they support careful prescribing and follow-up. Long-term safety data for repeated psychiatric use remain less established than acute safety data.

• Temporary dissociation or altered perception
• Dizziness, sleepiness or impaired coordination
• Nausea, vomiting or headache
• Anxiety, confusion or emotional discomfort
• Temporary increases in blood pressure or heart rate
• Potential misuse, dependence and uncertain long-term risks

How many treatments are needed, and how long do effects last?

A single ketamine treatment usually does not represent a complete treatment course. Early benefit after one dose can fade, and repeated sessions are commonly studied or used clinically to evaluate whether response becomes more consistent.

There is no universal schedule that is right for every patient or every formulation. If a person responds, continuation or maintenance treatment may be considered, with frequency adjusted according to benefit, adverse effects and clinical circumstances. Other parts of depression care—including medication, psychotherapy and relapse-prevention planning—may continue alongside treatment.

For esketamine, controlled relapse-prevention evidence suggests continued treatment can help sustain benefit among people who first responded. For racemic ketamine, the most appropriate long-term frequency, durability of benefit and long-term safety require further study, especially for routes other than intravenous administration.

Who may be a candidate?

Ketamine or esketamine may be considered for some adults whose depression has not improved sufficiently with appropriate conventional treatment. Suitability is not determined by symptom severity alone; the likely benefits must be weighed against medical, psychiatric and substance-related risks.

People on Vancouver Island or elsewhere in British Columbia who are considering treatment can ask NeuroLinks about assessment for intramuscular racemic ketamine or intranasal esketamine. NeuroLinks does not offer intravenous ketamine. An assessment can also explore other options, including transcranial magnetic stimulation, where appropriate.

Ketamine treatment is not a substitute for emergency care. Anyone at immediate risk of suicide or unable to stay safe should call 911, go to the nearest emergency department or contact an available crisis service. Do not wait for a clinic appointment.

To discuss whether an assessment may be appropriate, contact NeuroLinks or ask your health-care professional about referral requirements. Please do not send patient-identifying or confidential clinical details through public website forms.