Esketamine, a promising new nasal spray medication, is now FDA-approved for difficult-to-treat depression. It is the first major new antidepressant approved in decades. Some experts are concerned over the risk for misuse, but these concerns have been––for now––outweighed by the benefits of the drug: Esketamine acts fast (within hours) and improves symptoms of depression where other common antidepressants do not.

What is esketamine for?

Intranasal esketamine (brand name Spravato) is to be used in combination with antidepressant pills for difficult-to-treat depression. That is, depression which has not improved despite several back-to-back trials of different antidepressants.

16.2 million (6.7%) U.S. adults have had at least one major depressive episode. Of these, between 30% and 50% will have difficult-to-treat depression. The outlook for these folks is grim, and the risk of suicide is high.

How is esketamine related to ketamine?

If you thought esketamine sounded familiar, here’s why. It’s very closely related to the 50-year-old anesthetic ketamine. Ketamine has other uses too: It is (mis)used as a hallucinogenic party drug. At low doses, it can cause a rush of euphoria, but this can quickly change into “mind/body dissociation”, plunging users into what is known as the “k hole”––a scary state of near-paralysis somewhere between intoxication and coma.

Esketamine, a drug patented by Janssen, a subsidiary of Johnson & Johnson, is a molecule extracted from the ketamine molecule (ketamine is a mixture of two mirror-image molecules, and esketamine is one of them). It has the same effects as ketamine: it is a fast-acting antidepressant, which becomes hallucinogenic at higher doses.

How well does esketamine work compared to other popular antidepressants?

Traditional antidepressant pills can take 2 – 4 weeks to take effect. Several weeks can be a long time to wait for an improvement in symptoms, especially if the antidepressant causes side effects such as nausea, stomach upset, dry mouth, sleeplessness or drowsiness––which many do. Add to that frustration the fact that 60% – 70% of sufferers will not respond to the first treatment they try, and the situation can get pretty desperate.

The main benefit of esketamine is that it causes a fast––within hours and days––improvement in the symptoms of depression. This is a major shift in treatment options for sufferers who could feel that they are running out of options. The nasal spray helps esketamine get absorbed faster than taking a pill. It is given––in the doctor’s office––twice a week for the first month, and then every week or every other week after that.

So, a new antidepressant that works fast to save lives where others fail? What’s not to be excited about?

What are common side effects of esketamine?

Esketamine is not a miracle drug. It has a high risk for misuse, and higher doses can cause a frightening and dangerous state of “mind-body dissociation”, where the user cannot speak or move and can become psychotic or comatose in extreme cases.

Even under a doctor’s supervision, there is a risk of blood pressure spikes and distressing, “out-of-body” experiences, as well as headaches and nausea.

The thing that concerns some experts most about esketamine is the absence of long-term evidence about its safety.

There is also the fact that this new treatment plays into the current hype surrounding ketamine as some kind of miracle cure for depression. Some experts worry that the hype will discourage depression sufferers from trying traditional, safer first-line antidepressants, favoring instead the quick fix promised by esketamine.

How much does esketamine nasal spray cost?

The single 28mg dosage cost $600 with free shipping to your address if you live in the United States and Canada. Shipping SPRAVATO to the UK and Europe is also available and shipping time is 2 days.

SPRAVATO was studied in a robust Phase 3 clinical trial program with more than 1,700 adults with TRD. In a short-term study, those who took SPRAVATO™ and an oral antidepressant experienced superior improvement in depression symptoms at four weeks, compared to those who received a placebo and an oral antidepressant.1 In a long-term study, patients in stable remission taking SPRAVATO™ who continued treatment with the medicine were 51 percent less likely to relapse versus those who maintained a regimen of a placebo and an oral antidepressant.

SPRAVATO is a prescription medicine, used along with an antidepressant taken by mouth, for treatment-resistant depression (TRD) in adults.

SPRAVATO is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO is safe or effective as an anesthetic medicine.

It is not known if SPRAVATO is safe and effective in children.

The U.S. FDA granted Breakthrough Therapy designation for SPRAVATO for treatment-resistant depression. Janssen is also investigating the medicine for a second indication, major depressive disorder with imminent risk for suicide.7Janssen is currently conducting Phase 3 clinical studies for the second indication. Janssen submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication in October 2018 and anticipates approval later in 2019.


What is the most important information I should know about SPRAVATO™?

SPRAVATO™ can cause serious side effects, including:

Sedation and dissociation. SPRAVATO™ may cause sleepiness (sedation), fainting, dizziness, spinning sensation, anxiety, or feeling disconnected from yourself, your thoughts, feelings, space and time (dissociation).



Tell your healthcare provider right away if you feel like you cannot stay awake or if you feel like you are going to pass out.


Your healthcare provider must monitor you for serious side effects for at least 2 hours after taking SPRAVATO™. Your healthcare provider will decide when you are ready to leave the healthcare setting.

Abuse and misuse. There is a risk for abuse and physical and psychological dependence with SPRAVATO™ treatment. Your healthcare provider should check you for signs of abuse and dependence before and during treatment with SPRAVATO™.


Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.


Your healthcare provider can tell you more about the differences between physical and psychological dependence and drug addiction.

SPRAVATO™ Risk Evaluation and Mitigation Strategy (REMS). Because of the risks for sedation, dissociation, and abuse and misuse, SPRAVATO™ is only available through a restricted program called the SPRAVATO™ Risk Evaluation and Mitigation Strategy (REMS) Program. SPRAVATO™ can only be administered at healthcare settings certified in the SPRAVATO™ REMS Program and to patients enrolled in the program. 

Increased risk of suicidal thoughts or actions. SPRAVATO™ may cause worsening of depression and suicidal thoughts and behaviors, especially during the first few months of treatment and when the dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression or a history of suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions?


Pay close attention to any changes, especially sudden changes, in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions.


Tell your healthcare provider right away if you have any new or sudden changes in mood, behavior, thoughts, or feelings.


Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

Tell your healthcare provider right away if you have any of the following symptoms, especially if they are new, worse, or worry you:


attempts to commit suicide

worsening depression


thoughts about suicide or dying

other unusual changes in behavior or mood


SPRAVATO™ is not for use in children.

Do not take SPRAVATO if you:

  • have blood vessel (aneurysmal vascular) disease (including in the brain, chest, abdominal aorta, arms and legs)
  • have an abnormal connection between your veins and arteries (arteriovenous malformation)
  • have a history of bleeding in the brain
  • are allergic to esketamine, ketamine, or any of the other ingredients in SPRAVATO™.

If you are not sure if you have any of the above conditions, talk to your healthcare provider before taking SPRAVATO™.

Before you take SPRAVATO, tell your healthcare provider about all of your medical conditions, including if you:

  • have heart or brain problems, including:
    • high blood pressure (hypertension)
    • slow or fast heartbeats that cause shortness of breath, chest pain, lightheadedness, or fainting
    • history of heart attack
    • history of stroke
    • heart valve disease or heart failure
    • history of brain injury or any condition where there is increased pressure in the brain
  • have liver problems
  • have ever had a condition called “psychosis” (see, feel, or hear things that are not there, or believe in things that are not true).
  • are pregnant or plan to become pregnant. SPRAVATO™ may harm your baby. You should not take SPRAVATO™ if you are pregnant.
    • Tell your healthcare provider right away if you become pregnant during treatment with SPRAVATO™.
    • If you are able to become pregnant, talk to your healthcare provider about methods to prevent pregnancy during treatment with SPRAVATO™.
    • There is a pregnancy registry for women who are exposed to SPRAVATO™ during pregnancy. The purpose of the registry is to collect information about the health of women exposed to SPRAVATO™ and their baby. If you become pregnant during treatment with SPRAVATO™, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.
  • are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with SPRAVATO™.

Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking SPRAVATO™ with certain medicine may cause side effects. Especially tell your healthcare provider if you take Central Nervous System (CNS) depressants, psychostimulants, or Monoamine oxidase inhibitors (MAOIs) medicines.

How will I take SPRAVATO?

  • You will take SPRAVATO™ nasal spray yourself, under the supervision of a healthcare provider in a healthcare setting. Your healthcare provider will show you how to use the SPRAVATO™ nasal spray device.
  • Your healthcare provider will tell you how much SPRAVATO™ you will take and when you will take it.
  • Follow your SPRAVATO™ treatment schedule exactly as your healthcare provider tells you to.
  • During and after each use of the SPRAVATO™ nasal spray device, you will be checked by a healthcare provider who will decide when you are ready to leave the healthcare setting.
  • You will need to plan for a caregiver or family member to drive you home after taking SPRAVATO™.
  • If you miss a SPRAVATO™ treatment, your healthcare provider may change your dose and treatment schedule.
  • Some people taking SPRAVATO™ get nausea and vomiting. You should not eat for at least 2 hours before taking SPRAVATO™ and not drink liquids at least 30 minutes before taking SPRAVATO™.
  • If you take a nasal corticosteroid or nasal decongestant medicine, take these medicines at least 1 hour before taking SPRAVATO™.

What should I avoid while taking SPRAVATO?
Do not drive, operate machinery, or do anything where you need to be completely alert after taking SPRAVATO™. Do not take part in these activities until the next day following a restful sleep. See “What is the most important information I should know about SPRAVATO?”

What are the possible side effects of SPRAVATO?
SPRAVATO may cause serious side effects including:

  • See “What is the most important information I should know about SPRAVATO?
  • Increased blood pressure. SPRAVATO™ can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your healthcare provider will check your blood pressure before taking SPRAVATO™ and for at least 2 hours after you take SPRAVATO™. Tell your healthcare provider right away if you get chest pain, shortness of breath, sudden severe headache, change in vision, or seizures after taking SPRAVATO™.
  • Problems with thinking clearly. Tell your healthcare provider if you have problems thinking or remembering.
  • Bladder problems. Tell your healthcare provider if you develop trouble urinating, such as a frequent or urgent need to urinate, pain when urinating, or urinating frequently at night.

The most common side effects of SPRAVATO when used along with an antidepressant taken by mouth include:dissociation, dizziness, nausea, sedation, spinning sensation, reduced sense of touch and sensation, anxiety, lack of energy, increased blood pressure, vomiting, and feeling drunk.

If these common side effects occur, they usually happen right after taking SPRAVATO™ and go away the same day.

These are not all the possible side effects of SPRAVATO™.

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