Intra-Nasal Ketamine for Depression and Anxiety | ISHA Health

Science of Ketamine

Intra-Nasal Ketamine for Depression and Anxiety | ISHA Health

Written by

Isha Team


May 16, 2022


October 27, 2023

You may have heard of intranasal ketamine. More than one in 10 Americans take an antidepressant for depression. About one third of them have treatment-resistant depression. Intranasal Ketamine is specially formulated for them, which is marketed with the brand name Spravato, and contains esketamine hydrochloride. It is an N-methyl-D-aspartate (NMDA) receptor antagonist. It is administered in combination with oral antidepressants in people with depression to elevate mood and restore interest in daily life. As intranasal ketamine has the potential for abuse and its rapid effect is associated with sedation and dissociation, it is distributed under strict observation of Risk Evaluation and Mitigation Strategy (REMS).

Almost 16 million adults in the United States are affected by major depressive disorder (MDD), and 30% of them have treatment-resistant depression (TRD). The racemic mixture of intranasal ketamine and oral antidepressants are currently being used off-label in healthcare clinics. Spravato is an FDA-approved drug, its approval was granted to Janssen Pharmaceuticals, Inc in 2019.

This blog will detail intranasal Esketamine or Spravato.  

What are the Indications and Applications of Intranasal Ketamine?

Therapeutic Indications

  • In combination with SSRIs (Selective serotonin reuptake inhibitors) or SNRIs (Serotonin and norepinephrine reuptake inhibitors), intranasal ketamine is used to treat the treatment-resistant major depressive disorder (TRD) in adults who didn't respond to first and second-line treatment of depression.
  • It has been proven beneficial in relieving depressive symptoms and suicidal thoughts in major depressive disorder (MDD).
  • It is co-administered with oral antidepressant therapy to relieve depressive symptoms and as a short-term treatment in moderate to severe depressive episodes of Major depressive disorder.
  • According to clinical judgment, intranasal ketamine is used in psychiatric emergencies.

How is Intranasal Ketamine Administered?

Intranasal Ketamine is administered intranasally under the direct observation of a healthcare professional. It can be used only when prescribed by a doctor and can not be administered at home. The reason behind this restriction is the assessment of patients before and after using intranasal ketamine at healthcare clinics to avoid adverse effects associated with its administration.

Assessment before using Intranasal Ketamine

Blood pressure and intracranial pressure are checked before giving intranasal ketamine to patients because high blood and intracranial pressure can lead to serious complications.

Patients with serious cardiovascular diseases and respiratory problems are assessed before administration of intranasal ketamine, and it is not administered if equipment for cardiopulmonary and respiratory resuscitation and trained medical professionals are not available.

Spravato is contraindicated in the following conditions:

  • Hypersensitivity to Ketamine
  • High blood pressure (BP) and intracranial pressure (ICP) with serious complications
  • Vascular Aneurysms
  • Patients with recent intracerebral hemorrhage (stroke)
  • Recent (within 6 weeks) cardiovascular diseases such as myocardial infarction, heart attack, and valvular heart disease.
  • It may cause fetal harm during pregnancy.

Tell your doctor if you have psychosis (you hear, see, and feel things that are not present), liver problems, and pregnancy.

Post administration Assessment

After administering intranasal ketamine, blood pressure is assessed at the interval of 40 minutes for 2 hours and further If patients have high blood pressure. intranasal ketamine induces sedation and dissociation and elevates blood pressure. Patients are monitored by medical professionals until they are stable and are able to get discharged safely. You may need someone to drive you back home because it is most likely you won't be able to drive alone.

Due to these risks associated with the administration of Spravato, you can not use it at home without the supervision of health professionals.

How will you take Intranasal Ketamine?

  1. You'll take ketamine nasal spray under the direct observation of your doctor.
  2. Your doctor will guide you on how and how much you will administer intranasal ketamine.
  3. Your vitals will be assessed by healthcare professionals before leaving the healthcare clinic.
  4. In case of nasal stuffing, tell your doctor. If you use nasal decongestants, use them at least 1 hour before the administration of intranasal ketamine.
  5. In case of nausea and vomiting, don't eat at least 2 hours before taking intranasal ketamine, and don't take any fluids 30 minutes before administration of the drug.
  6. If you miss a dose of intranasal ketamine, your doctor may change the dose and treatment schedule.

How you take ketamine

Efficacy of Intranasal Ketamine and Oral Ketamine

Clinical trials and studies indicate the efficacy of intranasal ketamine in treating treatment-resistant depression (TRD) and MDSI. In long-term clinical trials, the majority of the patients showed a positive response to 84mg of intranasal ketamine. Approximately one-third of patients responded to 56mg of intranasal ketamine when administered weekly or every other week.

In a case series of oral Ketamine, 30% of patients showed improvement in symptoms of depression.

Moreover, it showed a transient increase in blood pressure and dissociation. Cognition returns within 2 hours of administration. Its efficacy beyond one year is still under clinical trials.

According to clinical trials and studies, Intranasal Ketamine has an established short-term efficacy as compared to oral Ketamines.


Intranasal Ketamine has 25-50% bioavailability while Oral Ketamine has a bioavailability of 16-24%.

What are the side effects?

Common warning signs of oral and Intranasal Ketamine include sedation, dissociation, abuse or misuse, cognitive impairment, impaired ability to concentrate (while driving and operating any machinery), ulcerative and interstitial nephritis (lower urinary tract symptoms), and embryo-fetal toxicity.

The most adverse reactions are dizziness, vertigo, anxiety, high blood pressure, nausea, vomiting, feeling drunk, spinning sensation, and lethargy(lack of energy).

What Is the Difference Between Oral Ketamine and  Intranasal ketamine?

Due to its slower absorption, low-dose oral ketamine can be administered safely at home.  Intranasal eskeatmine can be an effective treatment. If you had improvement of symptoms and would like to continue ketamine therapy at home, at home oral ketamine may be a good option for you.

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