Spravato Side Effects: What to Expect and When to Call Your Doctor

Spravato (esketamine) has a side effect profile that is quite different from traditional oral antidepressants. Its most distinctive effects — dissociation and sedation — occur acutely during and after each treatment session, which is a key reason the REMS program requires at least 2 hours of post-dose monitoring at every visit. Here's a comprehensive guide to what to expect.

Common Side Effects of Spravato (Esketamine)

The following side effects were commonly reported in clinical trials of Spravato for treatment-resistant depression (TRD). Most are acute — they occur during or shortly after the treatment session and resolve within a few hours:

Dissociation (28% in TRD, 48% in MDD with suicidal ideation): A feeling of detachment from your thoughts, feelings, body, or surroundings. This is the most characteristic side effect of esketamine and includes feelings of floating, depersonalization, derealization, and perceptual changes. It typically begins shortly after the first spray, peaks around 40 minutes, and fully resolves within 1–2 hours.

Dizziness (22% in TRD): May feel lightheaded or unsteady. This is why you must remain seated or lying down during the session.

Nausea and vomiting: Common, especially in the first few sessions. Fasting (no food 2 hours before, no liquids 30 minutes before) helps reduce nausea.

Sedation (48–61% of patients): Drowsiness is very common. This is monitored continuously during the session and is why patients cannot drive until the next day.

Headache: Reported in some patients; usually mild and temporary.

Anxiety: Some patients feel anxious during the dissociative experience. Clinical staff are present throughout the session to provide reassurance.

Feeling "drunk," detached, or "spaced out": These subjective experiences are part of the acute dissociative state and typically diminish with repeated sessions.

Nasal discomfort: Local nasal symptoms such as burning, irritation, or runny nose from the nasal spray administration.

Serious Side Effects: When to Get Help Immediately

Although rare, some Spravato side effects require immediate medical attention. These include:

Severe respiratory depression: Slowed or difficult breathing. In rare cases, respiratory arrest has been reported. This is why monitoring is required for 2+ hours after every session.

Loss of consciousness (0.3–0.4% of patients): Rare but possible. Treated on-site by clinical staff.

Severe hypertension: Spravato can elevate blood pressure during each session. If systolic BP reaches 180 mmHg or higher, or diastolic BP reaches 120 mmHg or higher, seek emergency medical care immediately.

New or worsening suicidal thoughts: Like all antidepressants, Spravato carries a boxed warning for increased suicidal thoughts or behaviors, particularly in patients under age 24. Call your doctor immediately if new suicidal thoughts occur.

Bladder problems: Ketamine-related bladder damage (ulcerative or interstitial cystitis) has been reported with long-term or high-dose ketamine use. Report any symptoms of painful, bloody, or frequent urination to your provider.

Signs of abuse or dependence: Spravato is a Schedule III controlled substance with abuse potential. Seek help immediately if you or someone around you notices compulsive drug-seeking behavior.

Boxed Warnings for Spravato

Spravato carries boxed warnings — the FDA's strongest safety warnings — for the following:

Sedation: In 48–61% of patients; 0.3–0.4% lose consciousness. Monitoring required for 2+ hours.

Dissociation: Includes perceptual disturbances, derealization, depersonalization. Routine occurrence with use.

Respiratory depression: Rare but serious. Risk is higher with concurrent CNS depressants.

Abuse and misuse: Schedule III substance; cannot be taken home; monitored at certified facilities only.

Does Dissociation Improve Over Time?

Yes — for most patients, dissociative symptoms attenuate (decrease) after repeated Spravato sessions. Clinical data shows that the severity of dissociation tends to be highest in the first few sessions and gradually lessens as treatment continues. Many patients find it manageable or even unremarkable by the maintenance phase of treatment.

Who Should NOT Take Spravato?

Spravato is contraindicated in patients with:

Hypersensitivity to esketamine, ketamine, or any excipients in the formulation

Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation

Use caution in: Active psychosis, uncontrolled hypertension, severe hepatic impairment, history of substance use disorder, pregnancy

Managing Your Medication With medfinder

Patients using Spravato often also take oral medications — antidepressants, anti-anxiety drugs, or sleep aids — that can be difficult to find at local pharmacies. medfinder calls pharmacies near you to find which ones have your prescriptions in stock, so you can focus on treatment without the stress of pharmacy hunting.

Also read: Spravato Drug Interactions: What to Avoid and What to Tell Your Doctor.