Esketamine nasal spray for Depression vs. Ketamine infusions?

Advantage of esketamine
nasal spray for depression

What is the advantage of esketamine nasal spray Spravato® for depression compared to IV ketamine infusion?

One might think that one advantage of esketamine nasal spray compared to intravenous ketamine infusions when treating mayor depression is, that one can self-administer the spray at home if needed. However, this is not the case: esketamine nasal spray Spravato® may only be administered by medical personnel. Patients must remain under medical observation for at least two hours after the administration.

Esketamine nasal spray Spravato® has been approved in the US for some time now and is now also approved by the EU Commission for the treatment of moderate to severe episodes of major depressive disorder (MDD), to support a therapy with oral antidepressants.
However, for ketamine to have an antidepressant effect, a certain serum concentration of ketamine must be present for a certain time.
Because ketamine is broken down very quickly in the body, esketamine nasal spray must be administered at a very high dose to achieve this high serum concentration of ketamine. The high dose of esketamine means that side effects may be more frequent and patients may need longer follow-ups. In addition, the risk of developing addiction is higher with fast-approaching serum concentrations.
With intravenous administration of Ketamine, this concentration is guaranteed from the beginning and can be adjusted at any time during the course of the infusion.

Janssen, the manufacturer of Spravato®, denies 2022 more common side effects. According to the European Medicines Agency, the following side effects are found with esketamine nasal spray Spravato®:

  • dizziness (31%)
  • dissociation (27%)
  • nausea (27%)
  • headache (23%)
  • somnolence (18%)
  • dysgeusia (18%)
  • vertigo (16%)
  • hypesthesia (11%)
  • vomiting (11%)
  • increased blood pressure (10%)

When ketamine is administered intravenously, the dose can be temporarily reduced at the first sign of an unpleasant side effect. This usually leads to an immediate stop of the symptoms. Physician and patient thus retain full control at all times. However, once the substance has been fully absorbed after nasal administration, this option is no longer available. The patient must wait until the side effects subside on their own. Unpleasant side effects are reported in less than 10% of all cases under medically supervised intravenous use.  Therefore, the follow-up time may be shorter than two hours.

In addition, esketamine nasal spray may be less effective than ketamine racemate used for infusions. This was suggested by the study by Bahji, Vazqeez, Zarate (2021), which concluded that intravenously administered ketamine appears to be more effective than intranasally administered esketamine in treating depression.
Janssen, however, disputes this.

In an updated data review, Bahij, Vazquez, and Zarate (2022) also no longer conclude that racemic ketamine is superior.
McIntyre et al (2021), in an international expert opinion, state that no clear superiority can be confirmed for either nasal esketamine or racemic i.v. ketamine; however, one study indicated superiority of i.v. ketamine.
However, in a meta-analysis of all randomized controlled trials of the anti-suicidal effects of ketamine and esketamine by Hochschild, Grunenbaum, and Mann (2021), the authors came to the sobering conclusion that esketamine nasal spray did not show a higher antisuicidal effect than placebo in any of the trials. Intravenous racemic ketamine, on the other hand, proved effective against suicidal ideation in all studies.

We have compiled recent studies about Ketamine treatment here.

Why is esketamine nasal spray recommended for depression?

This is for a simple reason: esketamine was patentable to the manufacturer, Jansson, making it appear to be a reputable and trustworthy medicine. Racemic ketamine, which is used in ketamine infusions in our clinic on Mallorca, has been on the market since 1970 and is therefore no longer patentable.
The cost per application for racemic ketamine is less than esketamine.
However, there is an additional expense due to the direct medical and psychotherapeutic support that is customary in our company.

So the advantage of esketamine nasal spray Spravato is that no vein needs to be punctured. Using Esketamine, side effects can be more frequent and patients must be under surveillance for at least as long as after an i.v. infusion with Ketamine. The antidepressant effect is possibly less strong and less sustained than with intravenous ketamine.

We always administer ketamine intravenously and also combine ketamine infusions with other therapeutic modalities such as magnetic stimulation (rTMS), neurofeedback, hypnosis and psychotherapy in the treatment of major depression and treatment-resistant depression. The Instituto Dr. Scheib in Mallorca is one of the few providers of this combined ketamine therapy, which promises an even faster and more stable improvement than ketamine infusions alone.
Ketamine infusions are also suitable for other clinical pictures: in patients with obsessive-compulsive disorders, chronic pain, as well as addictive disorders, this therapy is successful.

Our ketamine-assisted psychotherapy also achieves very good results in the case of complex post-traumatic stress disorders – in this case, however, the ketamine infusions are only ever offered together with disorder-specific psychotherapy.

Under certain circumstances, postpartum depression can also be treated with ketamine infusions, as the substance breaks down in the body within a few hours.

We offer intensive inpatient and outpatient therapies.
For a non-binding preliminary telephone consultation, or an appointment for a psychotherapeutic evaluation consultation for indication and therapy planning (subject to a fee, also possible online or by telephone) on Mallorca, contact us now:

Write to us using our contact form

You can also contact us by phone for appointments directly at the secretary’s office in our clinic in Spain at Tel: +34601906694


Video: Ketamine treatment and hypnosis for severe depression

Video: Patient with severe depression 3 Months after treatment