Esketamine Side Effects

Medically reviewed by Drugs.com. Last updated on Nov 21, 2024.

Applies to esketamine: nasal spray.

Precautions

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may cause prolonged drowsiness, loss of consciousness, mental changes (eg, confusion about identity, place, and time, feeling of unreality, sense of detachment from self or body), or high blood pressure. Your doctor will check for these effects for at least 2 hours after each treatment session.

This medicine may cause lung or breathing problems, including respiratory depression. Check with your doctor right away if you have irregular, fast or slow, or shallow breathing, pale or blue lips, fingernails, or skin, or trouble breathing. Your doctor will check for these effects for at least 2 hours after each treatment session.

Esketamine nasal spray may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Also tell your doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.

This medicine may make you drowsy, confused, or have problems with thinking clearly. Do not drive or do anything else that could be dangerous until the next day after a restful sleep or until you know how this medicine affects you. You may also need someone to drive you home after treatment with this medicine.

This medicine may cause bladder problems, including ulcerative or interstitial cystitis. Check with your doctor right away if you have bloody or cloudy urine, difficult, burning, or painful urination, or a frequent urge to urinate.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment with this medicine. If you think you have become pregnant while using this medicine, tell your doctor right away.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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:

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:

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]

See also:

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