Safety, side effects, and who should think twice

Common, expected side effects

During and shortly after a session, common effects include dissociation, dizziness, nausea or vomiting, higher blood pressure and heart rate, blurred vision, and sedation. Dissociation means feeling detached, dream-like, or floaty. Dissociation and sedation usually ease within about two hours. The blood-pressure rise from Spravato® peaks about 40 minutes after a dose and can last about four hours. That is why supervised settings watch you for at least two hours. They check that your blood pressure is coming down before you leave. After an IV infusion, you cannot drive for 24 hours, and some people feel tired for the rest of the day. The driving rules for IV ketamine and Spravato® are on our What to Expect page.

Less commonly, ketamine and esketamine can slow breathing (respiratory depression). Spravato®'s boxed warning covers five risks: sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.

That last one is the same warning every antidepressant carries. In pooled trials, antidepressants increased suicidal thoughts and behaviors in patients age 24 and younger. So anyone starting treatment should be watched closely for worsening mood or new suicidal thinking. The label says this matters most in the first few months and after any dose change. Family members or caregivers are asked to help watch for changes. Spravato® is not approved for anyone under 18.

Who should not get ketamine, and who needs caution

• Uncontrolled high blood pressure or significant cardiovascular disease. Ketamine temporarily raises both blood pressure and heart rate. Aneurysmal vascular disease, arteriovenous malformation, and a history of bleeding in the brain (intracerebral hemorrhage) are contraindications for Spravato®.
• History of psychosis or schizophrenia. Dissociative drugs can worsen psychotic symptoms. Most programs exclude these patients.
• Active substance use disorder. Ketamine has real misuse potential, so your history matters. It calls for a frank discussion with a clinician who takes it seriously. It does not automatically rule you out.
• Pregnancy and breastfeeding. Spravato®'s label says it is not recommended during pregnancy. That advice is based on animal data suggesting possible harm to the fetus. Breastfeeding is not recommended either. If you become pregnant during treatment, the label says esketamine should be stopped, so tell your prescriber right away. People who could become pregnant are advised to consider pregnancy planning and prevention during treatment. If you are pregnant, planning a pregnancy, or breastfeeding, tell the evaluating clinician. Untreated depression in pregnancy also carries risks, so decide this with your prescriber.
• Elevated intracranial pressure, moderate or severe liver disease, uncontrolled thyroid disease. Flag these in your evaluation. Spravato®'s label says not to dose if a rise in blood pressure or intracranial pressure would pose a serious risk. People with moderate liver impairment may need longer monitoring. It hasn't been studied in severe liver impairment, and the label does not recommend it there. Uncontrolled thyroid disease is a caution in the published ketamine consensus statements rather than in the label.

The FDA's warning on at-home compounded ketamine

On October 10, 2023, the FDA issued a compounding risk alert about compounded ketamine products marketed for psychiatric conditions, including the oral and sublingual forms often taken at home through telehealth programs. The alert is about compounded ketamine. It does not cover Spravato®, which is FDA-approved and given under a REMS with at least two hours of monitoring. Nor is it a finding that in-clinic IV ketamine is safe or effective; the FDA said ketamine's overall benefit-risk profile for psychiatric use is unknown. What the alert adds is the concern that at-home use removes on-site monitoring.

Our article on at-home ketamine therapy covers what the FDA found, how these programs work, and the questions to ask before you sign up.

Is ketamine addictive? Misuse and long-term risks

Chronic, frequent, high-dose ketamine use is associated with bladder damage (ulcerative cystitis), cognitive effects, and dependence. Those use patterns are seen in recreational misuse, not in standard clinical protocols. In Spravato® studies, urinary symptoms such as frequency, urgency, and painful urination were more common than with placebo. Still, no esketamine-related interstitial cystitis occurred in studies lasting up to a year. Cognitive testing stayed stable in open-label studies of up to three years. Data on years of maintenance treatment, especially with off-label IV or oral ketamine, are still limited. Report new urinary or bladder symptoms to your clinician. This is a reason to work with a program that measures response, uses the lowest effective frequency, and has stopping rules.

What proper monitoring looks like

• Blood pressure checked before and after dosing, with breathing and oxygen levels (pulse oximetry) monitored during observation.
• A clinician physically present or immediately available throughout.
• Emergency protocols and equipment on site.
• A required observation period before discharge.
• A no-driving rule that matches the drug label.
• Screening that asks about the contraindications above.

A program missing any of these has cut a corner on the part that keeps you safe. Our guide to choosing a clinic turns this list into questions to ask.