Esketamine Side Effects

Medically reviewed by Drugs.com. Last updated on Jan 31, 2025.

Applies to esketamine: nasal spray.

Important warnings This medicine can cause some serious health issues

Nasal route (spray)

Warning: Sedation; Dissociation; Respiratory Dissociation; Abuse and Misuse; and Suicidal Thoughts and Behaviors. Risk for sedation, dissociation, and respiratory depression after administration.

Monitor patients for at least 2 hours after administration.Potential for abuse and misuse.

Consider the risks and benefits of prescribing esketamine prior to using in patients at higher risk of abuse.

Monitor patients for signs and symptoms of abuse and misuse.Esketamine is only available through a restricted program call the SPRAVATO(TM) REMS.Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants.

Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors.

Esketamine is not approved for use in pediatric patients.

Serious side effects of esketamine

Along with its needed effects, esketamine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking esketamine:

More common side effects

• anxiety
• blurred vision
• confusion about identity, time, and place
• dizziness
• drowsiness
• feeling of constant movement of self or surroundings
• feeling of unreality
• headache
• lightheadedness
• nervousness
• pounding in the ears
• relaxed and calm feeling
• sensation of spinning
• sense of detachment from self or body
• sleepiness
• slow or fast heartbeat
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Less common side effects

• changes in patterns and rhythms of speech
• excitement
• false or unusual sense of well-being
• fast, pounding, or irregular heartbeat or pulse
• feeling abnormal or drunk
• frequent daytime urination
• nightmares or unusually vivid dreams
• slurred speech
• tremor
• trouble in speaking
• urinating small amounts of urine at a time

Rare side effects

• changes in behavior
• chest pain or discomfort
• discouragement
• fast or pounding heartbeat
• feeling sad or empty
• irritability
• lack of appetite
• loss of interest or pleasure
• sweating
• thoughts of killing oneself
• trouble concentrating
• trouble sleeping

Incidence not known

• irregular, fast or slow, or shallow breathing
• pale or blue lips, fingernails, or skin
• trouble breathing

Other side effects of esketamine

Some side effects of esketamine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common side effects

• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in or loss of taste
• diarrhea
• nasal itching, burning, or irritation
• nausea
• throat irritation
• vomiting

Less common side effects

• constipation
• dry mouth
• mouth or throat pain

For healthcare professionals

Applies to esketamine: nasal spray.

General adverse events

Nasal:

The most commonly reported side effects included dissociation, sedation, nausea, and dizziness.^[Ref]

Psychiatric

Nasal:

• Very common (10% or more): Dissociation (up to 75%), anxiety (up to 13%)
• Common (1% to 10%): Agitation, altered time perception, anxiety, derealization, euphoric mood, hallucination, illusion, insomnia, irritability, panic attack, visual hallucination
• Uncommon (0.1% to 1%): Suicidal ideation
• Frequency not reported: Anticipatory anxiety, auditory hallucination, delusional perception, depersonalization/derealization disorder, fear, nervousness, tension

Parenteral:

• Common (1% to 10%): Nightmares, vivid dreams
• Frequency not reported: Anxiety, disorientation, dysphoria, hallucinations^[Ref]

Dissociation (e.g., depersonalization, derealization, perceptual changed [distortion of time, place, and illusions]) occurred in up to 75% of patients 65 years and older given this drug PLUS oral antidepressant therapy.^[Ref]

Nervous system

Nasal:

• Very common (10% or more): Sedation (up to 61%), dizziness (up to 30%), headache (up to 24%), vertigo (up to 23%), dysgeusia (up to 19%), hypoesthesia (up to 18%), somnolence (up to 18%), lethargy (up to 11%)
• Common (1% to 10%): Dysarthria, mental impairment, paresthesia, tremor
• Frequency not reported: Altered state of consciousness, cognitive impairment, dizziness exertional, dizziness postural, dysesthesia, hypersomnia, hypogeusia, impaired ability to drive/operate machinery, procedural dizziness, sinus headache, slow speech, speech disorder, vertigo positional

Parenteral:

• Common (1% to 10%): Dizziness, increased brain pressure, motor restlessness
• Uncommon (0.1% to 1%): Clonic movements, convulsions, nystagmus, tonic movements^[Ref]

Sedation occurred in up to 61% of patients younger than 65 years given 84 mg of this drug intranasally PLUS oral antidepressant therapy.

Clonic and tonic movements resembling convulsions occurred as a result of increased muscle tonus in patients given parenteral formulations.

Increased brain pressure occurred in patients given parenteral formulations who were not under adequate ventilation.^[Ref]

Gastrointestinal

Nasal:

• Very common (10% or more): Nausea (up to 32%), vomiting (up to 12%)
• Common (1% to 10%): Constipation, diarrhea, dry mouth, oral hypesthesia, severe nausea, severe vomiting
• Uncommon (0.1% to 1%): Salivary hypersecretion
• Frequency not reported: Hypoesthesia teeth, oral dysesthesia, paresthesia oral

Parenteral:

• Common (1% to 10%): Increased salivation, nausea, vomiting^[Ref]

Nausea occurred in 32% of patients given 84 mg intranasal doses and 27% of patients given 56 mg intranasal doses. Severe nausea was reported in 3% of patients given 84 mg intranasal doses.

Vomiting occurred in 6% of patients given 84 mg intranasal doses and 12% of patients given 56 mg intranasal doses. Severe nausea was reported in 3% of patients given 84 mg intranasal doses.^[Ref]

Cardiovascular

Nasal:

• Very common (10% or more): At least 40 mmHg increase in systolic blood pressure (up to 17%), at least 25 mmHg increase in diastolic blood pressure (up to 14%)
• Common (1% to 10%): Blood pressure increased, diastolic blood pressure at least 110 mmHg, systolic blood pressure at least 180 mmHg, tachycardia
• Frequency not reported: Blood pressure diastolic increased, blood pressure systolic increased, extrasystoles, heart rate increased, hypertension

Parenteral:

• Common (1% to 10%): Blood pressure increase, heart rate increase, increased vascular resistance in pulmonary circulation, temporary tachycardia
• Rare (0.01% to 0.1%): Arrythmia, bradycardia, hypotension
• Very rare (less than 0.01%): Severe hypotension
• Frequency not reported: Circulatory shock^[Ref]

At least 25 mmHg increase in diastolic blood pressure occurred in up to 14% of patients 65 years and older given this drug PLUS oral antidepressant therapy.

At least 40 mmHg increase in systolic blood pressure occurred in up to 17% of patients 65 years and older given this drug PLUS oral antidepressant therapy.

Blood pressure and heart rate increases of 20% from baseline occurred in patients given parenteral formulations.

Hypotension in parenteral formulations occurred, especially with circulatory shock. Patients with shock developed further reductions in blood pressure.

Increased vascular resistance in pulmonary circulation occurred with parenteral formulations, especially in those with restricted coronary reserve.^[Ref]

Respiratory

Nasal:

• Common (1% to 10%): Nasal crusting, nasal discomfort, nasal dryness, nasal pruritus, oropharyngeal pain, pharyngeal paresthesia, throat irritation

Parenteral:

• Common (1% to 10%): Laryngospasm, temporary respiratory depression^[Ref]

Dose and rate of injection were correlated with the risk of respiratory depression.^[Ref]

Other

Nasal:

• Common (1% to 10%): Feeling abnormal, feeling drunk, feeling of body temperature change, hyperacusis, tinnitus
• Frequency not reported: Embryofetal toxicity, fatigue, feeling cold, feeling hot, feeling jittery

Parenteral:

• Common (1% to 10%): Increased mucus secretion, recovery reactions^[Ref]

Increased mucus secretion occurred with parenteral formulations, especially in those with restricted coronary reserve.^[Ref]

Genitourinary

Nasal:

• Common (1% to 10%): Dysuria, micturition urgency, pollakiuria
• Frequency not reported: Interstitial cystitis, ulcerative cystitis^[Ref]

Ocular

Nasal:

• Common (1% to 10%): Blurred vision
• Frequency not reported: Diplopia, ocular discomfort, photophobia, visual impairment

Parenteral:

• Common (1% to 10%): Blurred vision
• Uncommon (0.1% to 1%): Diplopia, increased intraocular pressure^[Ref]

Local

Parenteral:

• Common (1% to 10%): Hyperreflexia, laryngeal spasms
• Uncommon (0.1% to 1%): Injection site erythema, injection site pain^[Ref]

Hyperreflexia and laryngospasm may occur in parenteral formulations with upper respiratory tract diagnostic and/or therapeutic interventions, especially in pediatric patients; muscle relaxation with adequate ventilation may be needed in procedures involving the bronchial tree, larynx, and/or pharynx.^[Ref]

Dermatologic

Nasal:

• Common (1% to 10%): Hyperhidrosis

Parenteral:

• Uncommon (0.1% to 1%): Exanthema, morbilliform rash^[Ref]

Musculoskeletal

Nasal:

• Uncommon (0.1% to 1%): Muscular weakness

Parenteral:

• Common (1% to 10%): Increased muscle tone^[Ref]

Increased muscle tone occurred in patients given parenteral formulations who were not under adequate ventilation.^[Ref]

Hypersensitivity

Parenteral:

• Rare (0.01% to 0.1%): Anaphylaxis
• Very rare (less than 0.01%): Anaphylactoid reactions, hypersensitivity reactions^[Ref]

Hepatic

Parenteral:

• Frequency not reported: Abnormal liver function tests, drug-induced liver injury^[Ref]

Drug-induced liver injury occurred in extended use (e.g., greater than 3 days) and/or with abuse.^[Ref]

Metabolic

Parenteral:

• Common (1% to 10%): Increased oxygen consumption^[Ref]

Frequently asked questions

• Is Spravato (esketamine) a controlled substance?

Further information

Esketamine side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer