Ketamine IV vs Esketamine Nasal Spray: Which is Better for You?

Last updated: December 31, 2020
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Have you been prescribed a cocktail of antidepressants or experienced ECT or TMS yet nothing seems to work?

For many years, ketamine IV infusion has been widely used for Treatment-Resistant Depression (TRD). Recently, the FDA recently approved Spravato esketamine intranasal spray for TRD, too. In light of this latest development, medical practitioners have started to prescribe Spravato, a tradename of esketamine. Like Ketamine IV, Spravato can only be used under the supervision of a clinician in a medical facility. Should you have questions about esketamine and Ketamine IV infusion therapy, you may contact the Injection and Infusion Clinic of ABQ505 455 4300. Many studies have been published about the safety and efficacy of ketamine IV. Esketamine is a partial form of ketamine IV known as an isomer. This version has also been researched. The latest study shows long-term esketamine nasal spray coupled with an oral antidepressant appeared to be safe. Depressive symptoms continued to improve among the 603 participants. 

Here are the 5 differences between Ketamine IV and Nasal Spray:

1. Pros and cons on the administration of Ketamine

Ketamine IV: The infusion takes about 40 minutes to an hour. The IV form is 100% bioavailable.

Nasal spray: It takes a few minutes to administer the nasal spray. There is some loss as some may drip out of your nose or down your throat. This makes it less bioavailable. The FDA requires that you be observed for 2hours after administration of the nasal spray.

2. Efficacy and scope of therapy

Ketamine IV: It has a proven track record as a therapy for TRD (Please link to any blog that presents benefits etc.). It has rapid effects as ketamine is injected directly into the bloodstream. It has long-lasting results with intermittent or booster infusions. Studies have shown that Ketamine IV is also effective for other mood disorders such as anxiety, postpartum depression, bipolar disorder, suicidal ideation, and post-traumatic stress disorder (Please link to any blog about the following disorders). 

Nasal spray: It has to pass layers of tissues before it takes effect. But it has a rapid antidepressant effect. Moreover, esketamine plus antidepressants showed to be effective in preventing relapse of TRD. It performs better than oral antidepressants with placebo.

3. Dosage and schedule of therapy

The dosage and schedule of therapy may vary slightly depending on the healthcare provider. For details on ketamine IV infusion therapy, call us at Injection and Infusion Clinic of ABQ505 455 4300.

Ketamine IV: Dose 0.5mg-1mg per kilogram, 5-6 infusions over 2-3 weeks, and boosters every 4-6 weeks. Some long-time ketamine infusion patients are able to prolong the time between their boosters.

Nasal spray: Dose 56 mg or 84 mg, 2 times a week for 4 weeks, and maintenance every 1-2 weeks 

4. Cost

The price of Ketamine IV and esketamine depends on the brand and frequency of use. The Institute for Clinical and Economic Review conducted a cost-analysis comparison between ketamine and esketamine for the treatment of TRD. The results show that esketamine is more costly than ketamine.

In a more recent study, researchers at McClean Hospital conducted a cost-effective analysis of esketamine nasal spray. The result also showed that esketamine nasal spray is too expensive.

5. Health insurance coverage

Ketamine IV and nasal spray are not yet covered by health insurance.Other than differences, Ketamine IV and nasal spray share some commonalities. Ketamine IV infusion has potential side effects and risks.For ketamine nasal spray, there are reported cases of treatment-emergent adverse events (TEAE). The researchers noted dissociation, nausea, and headache during a 60-week study. They further reported 6.9% of participants with serious TEAEs.Ketamine nasal spray like IV is safe and tolerated by the body. You still have to be aware of its potential risks. The FDA listed warnings on the use of Spravato. Here are the more common 7 warnings or potential side effects or risks.

7 Warnings

1. Sedation

You may feel sleepy or sedated. Sedation is one of the most commonly observed adverse reactions of Spravato. It also includes anxiety, dizziness, hypertension, hypoesthesia, lethargy, nausea, and vomiting. 49% to 61% of people treated with Spravato developed sedation based on clinical trials. Sedation, dizziness, dissociation, and increased blood pressure were also reported 2 hours after the use of Spravato. Sedation can worsen with drug-to-drug interactions. Central nervous system depressants include alcohol, benzodiazepines, and opioids.

2. Dissociation

You may feel disconnected from yourself – physically, psychologically, and environmentally. This is also called dissociation. Dissociative or perceptual changes are the most common psychological effect of Spravato. Its use should be seriously be avoided if a person is concurrently suffering from psychotic or other mental disorders. Spravato may aggravate the pre-existing mental condition.

3. Suicidal thoughts among teenagers and young adults

Spravato may be good for adults in the treatment of TRD with acute suicidal ideation or behavior. In fact, Spravato is a treatment for TRD with acute suicidal ideation or behavior.A study finds that suicidal thoughts decreased with a Spravato dose of 84 mg at 4 hours, but not at 24 hours or 25 days. Yet suicidal thoughts or behavior can be aggravated by Spravato among teenagers and young adults with depression and major depressive disorder. Based on placebo-trial studies on antidepressants, a review reveals that young people are at risk more than adults. Although, it is still unknown if the risk of suicidal thoughts and behaviors is long-term.There is an ongoing study to further test the efficacy and safety of Spravato to adolescents aged 12-18 years old who have major depressive disorder including suicidal ideation.

4. Increase in blood pressure

Based on the drug literature, Spravato may increase blood pressure by 40 mmHg systolic and 20 mmHg in all doses. This peaks at about 40 minutes after administration. Blood pressure will typically normalize prior to discharge home. Brief increases in blood pressure and heart rate have been observed in other studies as well. According to the FDA, other drugs that can induce hypertension are psychostimulants such as amphetamines and modafinil, and monoamine oxidase inhibitors such as phenelzine and selegiline.

5. Impaired cognitive ability

Spravato may affect your short-term more than your long-term cognitive or intellectual ability. A study reveals that Spravato affected the cognitive ability among healthy people 40 minutes after a single dose. The placebo group did better in a cognitive test. It took two hours post-dose before the Spravato group recovered to placebo-level performance. No long-term effect on cognition was described within a one-year open-label safety study. But it has been reported among people who repeatedly misused or abused ketamine.

6. Impaired ability to drive or use machinery

Twenty-four healthy people participated in a study to determine the effects of Spravato 84 mg on driving performance. The researchers found no marked difference in the driving performance 8 hours post-dose. You may still be at a risk of injury due to possible impaired motor coordination and mental alertness. Driving and operating machinery are examples of activities that are not allowed after Spravato therapy.

 7. Potential for abuse and misuse

Spravato belongs to Schedule III controlled substance (CII) due to its esketamine ingredient. Thus, it has the potential for abuse or misuse. The FDA differentiates abuse from misuse. Abuse is intentional and recreational or illicit drug use. People abuse a drug for their physical or psychological effects. Misuse is also deliberate but for medical or therapeutic purposes. But the person uses it in a way other than its main purpose. Or it may have been prescribed to someone else.Schedule III drugs means it may cause moderate or low physical dependence or high psychological dependence. The Comprehensive Drug Abuse Prevention Control Act of 1970, a federal drug policy defines Controlled Substance Act II. Spravato belongs to drugs that are regulated in terms of manufacturing, distribution, importation, possession, and use.Spravato has opioid properties that warrant further investigation in considering the best way to safely use it. This has also been an expert opinion of researchers who reviewed clinical trials on Spravato. They concluded that Spravato benefits people with TRD due to its rapid onset. But the main concern is safety with prolonged use.

  • Abuse: A study assessed the potential abuse of Spravato at 84 mg doses compared with racemic ketamine IV infusion at 112 mg. The study also aimed to measure drug volume of distribution, maximum concentration, peak, half-life, and clearance. Thirty-four recreational polydrug users participated in the study. Results reveal that Spravato users showed higher scores for “detached,” “floating,” “hallucination,” and “spaced out” compared to IV ketamine users.  
  • Dependence: The prolonged use of ketamine abuse may cause physical dependence according to reports. Physical dependence results from the body’s reaction to the repeated use of the drug. It can manifest as withdrawal symptoms when the drug is abruptly lowered or stopped. Unlike the abuse dosing, withdrawal symptoms were not observed up to four weeks after the use of Spravato. In over three years of providing ketamine IV, we have not observed withdrawal symptoms in our patients.

Which is better for you?

Ketamine IV and nasal spray are rapid-acting, safe, and effective for TRD. They have differences and similarities. And they have their respective pros and cons. Before deciding on any therapy, talk to us for a more detailed discussion on ketamine. Our Ketamine-certified clinicians have administered more than 2,000 ketamine infusions since 2017. You may visit us at the Injection and Infusion Clinic of ABQ in Albuquerque, Santa Fe, Rio Rancho, Tijeras, Edgewood. Or drop a comment below and we’ll get back to you.

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