SPRAVATO
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How does Spravato help depression?
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What are the side effects of Spravato?
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What are the dissociative and psychomimetic effects of Spravato?
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What is the treatment schedule of Spravato?
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How do you manage the side effects of Spravato?
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Will I become addicted to Spravato?
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FDA Approved Treatment for Depression
FDA approved for treatment of depressive symptoms in adults with major depressive disorder, treatment-resistant depression, and depression with suicidal thoughts or actions.
What is Spravato?
1) Andrade, C. (2017). Ketamine for depression, 3: does chirality matter?. The Journal of clinical psychiatry, 78(6), 10104.
Spravato (esketamine) is a rapid acting, nasal spray indicated for the treatment of treatment-resistant depression (TRD) and depressive symptoms in adults with major depressive disorder (MDD).
Ketamine is a dissociative anesthetic that was FDA approved in 1970. Ketamine is actually a mixture of two molecules that are mirror images of each other called enantiomers. The two molecules are S-ketamine and R-ketamine. S-ketamine is also known as esketamine or Spravato.
Is Spravato FDA approved?
Spravato was approved by the FDA in March 2019 to be used in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults. In August 2020, the FDA updated the approval of Spravato to include adults with major depression and suicidal ideation and behavior.
1) United States Food and Drug Administration approved labelling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024) 2) McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., Sanacora, G., Murrough, J. W., Berk, M., ... & Stahl, S. (2021). Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. American Journal of Psychiatry, 178(5), 383-399.
How is Spravato administered?
1) United States Food and Drug Administration approved labelling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024)
Spravato is delivered as a nasal spray under the supervision of a healthcare provider in a healthcare setting. The visit will take two hours.
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You will need to plan for a caregiver or family member to drive you home after taking SPRAVATO.
You should not eat for at least 2 hours before taking SPRAVATO and not drink liquids at least 30 minutes before taking SPRAVATO.​
How does Spravato help depression?
1) Schatzberg, A. F., & Nemeroff, C. B. (Eds.). (2017). The American psychiatric association publishing textbook of psychopharmacology. American Psychiatric Pub. 2) Singh, J. B., Fedgchin, M., Daly, E., Xi, L., Melman, C., De Bruecker, G., ... & Van Nueten, L. (2016). Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biological psychiatry, 80(6), 424-431. 3) Williams, N. R., Heifets, B. D., Blasey, C., Sudheimer, K., Pannu, J., Pankow, H., ... & Schatzberg, A. F. (2018). Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. American Journal of Psychiatry, 175(12), 1205-1215. 4) Chen, M. H., Li, C. T., Lin, W. C., Hong, C. J., Tu, P. C., Bai, Y. M., ... & Su, T. P. (2018). Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: a randomized control study. Journal of affective disorders, 225, 709-714. 5) Deyama, S., Bang, E., Wohleb, E. S., Li, X. Y., Kato, T., Gerhard, D. M., ... & Duman, R. S. (2019). Role of neuronal VEGF signaling in the prefrontal cortex in the rapid antidepressant effects of ketamine. American Journal of Psychiatry, 176(5), 388-400.
How Spravato helps depression is not fully understood and functions in the same way as ketamine. Spravato binds to multiple receptors in the brain and therefore has the potential to exert several different effects in the brain. Some of the receptors include:
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N-methyl-D-aspartate (NMDA) Receptor
The NMDA receptor is the primary target of the brain’s excitatory neurotransmitter glutamate. Spravato has the effect of antagonizing the NMDA receptor and thereby blocking glutamate’s excitatory effect. Spravato (esketamine) binds to NMDA receptors with much greater affinity than ketamine.1,2
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Opioid Receptor
Spravato binds to and activates opioid receptors. A study looked at ketamine therapy for depression in two groups. One group received naltrexone before ketamine administration. Naltrexone binds to and blocks opioid receptors. The other group received a placebo before ketamine administration. The naltrexone group did not see improvement in depression symptoms to the same effect that the placebo group did.3
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Additionally, Spravato activates the anterior cingulate cortex of the brain and appears to activate neuronal vascular endothelial growth factor in the prefrontal cortex.4,5
What are the side effects of Spravato?
1) Andrade, C. (2017). Ketamine for depression, 3: does chirality matter?. The Journal of clinical psychiatry, 78(6), 10104. 2) Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2018). Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry, 5(1), 65-78. 3) Singh, J. B., Fedgchin, M., Daly, E. J., De Boer, P., Cooper, K., Lim, P., ... & Van Nueten, L. (2016). A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. American Journal of Psychiatry, 173(8), 816-826.
Side effects of Spravato are similar to ketamine, except that dissociation and psychomimetic effects occur less frequently with Spravato compared to ketamine.
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Side effects include elevated heart rate and blood pressure, anxiety, nausea and vomitting. These are carefully monitored during administration and medication is on hand to address each of these side effects individually.
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Other side effects may include sedation, chest pain or pressure, palpitations, dizziness, headache, blurred vision and respiratory depression.
What are dissociative and psychomimetic effects of Spravato?
Dissociation is a mental process of disconnecting from one's thoughts, feelings, memories or sense of identity.
A drug with psychotomimetic actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations.
These effects are interpreted subjectively by the individual and can fall within a spectrum from positive to negative experience. Interpreting a psychotomimetic symptom in a negative way is spoken of as having a “bad trip”.
What is the treatment schedule for Spravato?
1) United States Food and Drug Administration approved labelling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024)
How do you manage the side effects of Spravato during treatment?
1) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Text Revision. Arlington, VA: American Psychiatric Association; 2022.
We closely monitor your vital signs during IV ketamine infusion to ensure your blood pressure, heart rate, and oxygen remain at stable levels. Medication is on hand to lower blood pressure and heart rate should it become necessary.
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Medication is available to treat any anxiety that may occur during treatment sessions. We also have medication to address the nausea and vomiting that could arise.
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Should dissociations become an issue during therapy, a certified therapist can attend to you during treatment sessions to provide reassurance and counseling that may address underlying behavioral issues.
IV ketamine vs nasal esketamine (Spravato).
1) Bahji, A., Vazquez, G. H., & Zarate Jr, C. A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. Journal of affective disorders, 278, 542-555. 2) Singh, J. B., Fedgchin, M., Daly, E., Xi, L., Melman, C., De Bruecker, G., ... & Van Nueten, L. (2016). Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biological psychiatry, 80(6), 424-431. 3) Andrade, C. (2017). Ketamine for depression, 3: does chirality matter?. The Journal of clinical psychiatry, 78(6), 10104.
Both IV ketamine and nasal esketamine (Spravato) are effective at treating depression and suicidal ideations. A systematic review of 24 trials including 1,877 concluded that "IV ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression."1
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However, esketamine (Spravato) is four times more potent than ketamine. This means that a lower dose may be used to achieve the same results. This has the benefit of reducing the dissociative and psychomimetic effects of therapy inherent with IV ketamine. Many people find this appealing.
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Spravato is FDA approved and covered by many insurances. IV ketamine is not FDA approved though it is accepted as a mainstream treatment. It is therefore not covered by insurance and must be paid for out of pocket.
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I would personally try esketamine (Spravato) before IV ketamine because of the reduced risk of side effects and decrease abuse potential.
Will I become addicted to Spravato?
1) •United States Food and Drug Administration approved labelling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024)
Tolerance to Spravato can occur requiring progressively larger doses and increased frequency leading to Spravato dependence.
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There are concerns that Spravato dependence through long term treatment could potentially lead to a new drug epidemic as has occurred with opioid pain medication.
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Because of the potential euphoric and hallucinogenic properties of ketamine, especially at higher doses, there is the potential for abuse. Additionally, Spravato reacts with opioid receptors so caution must be exercised in those with a history of opiate abuse.
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"Because of the risks of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, Spravato is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Spravato REMS."
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This means that your treatment with Spravato is carefully monitored and controlled in order to take every precaution necessary to avoid abuse, dependence, and addiction.
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We don't deny treatment to individuals with a history of substance abuse or addiction. We follow the FDA guidelines to “use careful consideration prior to treatment of individuals with a history of substance use disorder and monitor for signs of abuse or dependence.”​
Will I become addicted to ketamine?
1) United States Food and Drug Administration approved labelling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024) 2) Freedman, R., Brown, A. S., Cannon, T. D., Druss, B. G., Earls, F. J., Escobar, J., ... & Xin, Y. (2018). Can a framework be established for the safe use of ketamine?. American Journal of Psychiatry, 175(7), 587-589. 3) Schak, K. M., Vande Voort, J. L., Johnson, E. K., Kung, S., Leung, J. G., Rasmussen, K. G., ... & Frye, M. A. (2016). Potential risks of poorly monitored ketamine use in depression treatment. American Journal of Psychiatry, 173(3), 215-218.
Tolerance to ketamine can occur requiring progressively larger doses and increased frequency leading to ketamine dependence.
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There are concerns that Ketamine dependence through long term treatment could potentially lead to a new drug epidemic as has occurred with opioid pain medication.
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Because of the potential euphoric and hallucinogenic properties of ketamine, especially at higher doses, there is the potential for abuse. Additionally, ketamine reacts with opioid receptors so caution must be exercised in those with a history of opiate abuse. Ketamine has long been used recreationally.
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Because of its potential for abuse, we do not offer ketamine therapy for home administration. It is administered in office under the direction of the prescribing physician. Our goal is to treat you with as little ketamine as seldom as required for you to maintain proper mental health.
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We don't deny treatment to individuals with a history of substance abuse or addiction. We follow the FDA guidelines to “use careful consideration prior to treatment of individuals with a history of substance use disorder and monitor for signs of abuse or dependence.”​
Will I become addicted to Spravato?
1) United States Food and Drug Administration approved labelling.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf (Accessed on February 7, 2024) 2) Freedman, R., Brown, A. S., Cannon, T. D., Druss, B. G., Earls, F. J., Escobar, J., ... & Xin, Y. (2018). Can a framework be established for the safe use of ketamine?. American Journal of Psychiatry, 175(7), 587-589. 3) Schak, K. M., Vande Voort, J. L., Johnson, E. K., Kung, S., Leung, J. G., Rasmussen, K. G., ... & Frye, M. A. (2016). Potential risks of poorly monitored ketamine use in depression treatment. American Journal of Psychiatry, 173(3), 215-218.
Tolerance to ketamine can occur requiring progressively larger doses and increased frequency leading to ketamine dependence.
​
There are concerns that Ketamine dependence through long term treatment could potentially lead to a new drug epidemic as has occurred with opioid pain medication.
​
Because of the potential euphoric and hallucinogenic properties of ketamine, especially at higher doses, there is the potential for abuse. Additionally, ketamine reacts with opioid receptors so caution must be exercised in those with a history of opiate abuse. Ketamine has long been used recreationally.
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"Because of the risks of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, SPRAVATO is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SPRAVATO REMS."1
Our goal is to treat you with as small a dose and as seldom as required for you to maintain proper mental health. We don't deny treatment to individuals with a history of substance abuse or addiction. We follow the FDA guidelines to “use careful consideration prior to treatment of individuals with a history of substance use disorder and monitor for signs of abuse or dependence.”​1
Can I die from Spravato?
1) Dalton, A. (2023, December 15). Matthew Perry died from the effects of ketamine, autopsy report says. APNews. https://apnews.com/article/matthew-perry-death-cause-054e67f7495845804f801c57a1ae2522
Absolutely! Spravato, like any other medication, can be lethal when not used appropriately. However, the use of ketamine under the proper direction and supervision of a physician has been proven to be quite safe.
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The recent death of actor Matthew Perry has drawn attention to the safety of ketamine therapy. This is not a bad thing. People need to be aware of the danger associated with abusing ketamine.
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According to the medical examiner, "levels of ketamine in Perry’s body were in the range used for general anesthesia during surgery, and that his last treatment 1 1/2 weeks earlier wouldn’t explain those levels."1
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It appears as though Matthew Perry was using ketamine outside the direction of a physician and certainly not under the supervision of one.
We only administer Spravato in office. We do not send you home with Spravato. We have medication on hand to control heart, blood pressure, respiratory depression, anxiety, nausea and vomiting that may occur during treatment. We take your safety very seriously.