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IV ketamine for treatment resistant depression in st george utah.

"Research on ketamine has shown that single-dose, off-label use of this drug can provide rapid-acting, relief for patients with treatment resistant depression.  Traditional antidepressant treatments may take 4–8 weeks or longer to take effect, while a single dose of ketamine can do so in a matter of hours or days."

S. Parikh MD, Psychopharmacology Bulletin, June 2021

IV
Ketamine

Effective, Rapid Therapy for Treatment Resistant Depression and Suicidal Ideation

IV ketamine helps depression
IV ketamine for suicidal thoughts and depression st george utah

The irony of the term "treatment-resistant depression" can add insult to injury to those who have sought to alleviate persistent symptoms of depression and found no relief.  For those who are plagued with recurrent thoughts of suicide, the hopelessness that there is nowhere to turn only deepen the emotional pain from which suicide seems to be the only relief. 

 IV ketamine and intranasal esketamine (Spravato) are powerful treatment options that have the potential to relieve symptoms of depression and / or suicidal ideation within two hours of administration.  Two hours could be the difference between life and death in your life or in the life of someone you love.

 

IV ketamine treatment options st geoge utah
spravato treatment options st george utah

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What is Ketamine?

1) Andrade, C. (2017). Ketamine for depression, 3: does chirality matter?. The Journal of clinical psychiatry, 78(6), 10104.

Ketamine is a dissociative anesthetic that has been used for years to induce and maintain anesthesia.  Additionally, it has properties as an analgesic (pain reliever) and an anti-depressant.  It has gained popularity as an effective medication to address treatment resistant depression and suicidal ideation in individuals. 

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. 

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How does Ketamine 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 ketamine helps depression is not fully understood.  Ketamine 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:

N-methyl-D-aspartate (NMDA) Receptor

The NMDA receptor is the primary target of the brain’s excitatory neurotransmitter glutamate.  Ketamine 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

Opioid Receptor

Ketamine 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

Additionally, ketamine activates the anterior cingulate cortex of the brain and appears to activate neuronal vascular endothelial growth factor in the prefrontal cortex.4,5

How is Ketamine administered?

Ketamine is usually administered by IV infusion or nasally.  For nasal administration visit the Spravato (esketamine) page.

 

For IV infusion of ketamine, 0.5 mg/kg is the most common starting dose given over a 40 minute period. 

1) Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., ... & American Psychiatric Association. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA psychiatry, 74(4), 399-405. 2) Fava, M., Freeman, M. P., Flynn, M., Judge, H., Hoeppner, B. B., Cusin, C., ... & Papakostas, G. I. (2020). Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Molecular psychiatry, 25(7), 1592-1603.

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How often is IV ketamine administered?

1) Loo, C. (2018). Can we confidently use ketamine as a clinical treatment for depression?. The Lancet Psychiatry, 5(1), 11-12. 2) Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., Nemeroff, C. B., & APA Council of Research Task Force on Novel Biomarkers and Treatments. (2015). Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. American Journal of Psychiatry, 172(10), 950-966. 3) Malhi, G. S., Byrow, Y., Cassidy, F., Cipriani, A., Demyttenaere, K., Frye, M. A., ... & Tohen, M. (2016). Ketamine: stimulating antidepressant treatment?. BJPsych Open, 2(3), e5-e9. 4) Andrade, C. (2017). Ketamine for depression, 4: in what dose, at what rate, by what route, for how long, and at what frequency?. The Journal of clinical psychiatry, 78(7), 10106.

It is not clear how frequently IV ketamine should be administered. Once or twice weekly dosing is the current general consensus . Ketamine's effect on depression appears to decrease within 2 weeks following treatment. 

Patients who do not respond to a single infusion of ketamine may see improvement with subsequent infusions.  

 

We have found success with a "loading dose" of 6 treatment spaced over 2-3 weeks.   This is followed by maintenance treatments at a personalized rate based on your individualized needs. 

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How quickly does ketamine relieve symptoms of depression?

50% of patients with treatment resistant depression see results within 40 to 120 minutes of IV ketamine treatment. 

69% of patients who continue on ketamine twice a week see a 50% reduction in symptoms of depression within two weeks. 

1) Fond, G., Loundou, A., Rabu, C., Macgregor, A., Lançon, C., Brittner, M., ... & Boyer, L. (2014). Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology, 231, 3663-3676. 2) Xu, Y., Hackett, M., Carter, G., Loo, C., Gálvez, V., Glozier, N., ... & Rodgers, A. (2016). Effects of low-dose and very low-dose ketamine among patients with major depression: a systematic review and meta-analysis. International Journal of Neuropsychopharmacology, 19(4), pyv124. 3) Caddy, C., Amit, B. H., McCloud, T. L., Rendell, J. M., Furukawa, T. A., McShane, R., ... & Cipriani, A. (2015). Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database of Systematic Reviews, (9). 4) 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.

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How long should I stay on ketamine?

1) Andrade, C. (2017). Ketamine for depression, 4: in what dose, at what rate, by what route, for how long, and at what frequency?. The Journal of clinical psychiatry, 78(7), 10106.

After the "loading dose", maintenance treatments are based on your individual needs.  There is not much research on how often an individual should continue to stay on ketamine.  

For example, ketamine is very effective as a "rescue" medication for treatment resistant depression and suicidal ideation.  If one or more sessions of ketamine help relieve your symptoms, you hopefully will not require further treatments.  If symptoms return, you may find that additional treatments are necessary to maintain proper mental health. 

Our goal is that you feel your best using as little medications as possible. 

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What are the side effects of IV ketamine?

1) 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. 2) 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. 3) Kishimoto, T., Chawla, J. M., Hagi, K., Zarate, C. A., Kane, J. M., Bauer, M., & Correll, C. (2016). Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychological medicine, 46(7), 1459-1472. 4) Grunebaum, M. F., Galfalvy, H. C., Choo, T. H., Keilp, J. G., Moitra, V. K., Parris, M. S., ... & Mann, J. J. (2018). Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. American Journal of Psychiatry, 175(4), 327-335. 5) Su, T. P., Chen, M. H., Li, C. T., Lin, W. C., Hong, C. J., Gueorguieva, R., ... & Krystal, J. H. (2017). Dose-related effects of adjunctive ketamine in Taiwanese patients with treatment-resistant depression. Neuropsychopharmacology, 42(13), 2482-2492. 6) Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., Nemeroff, C. B., & APA Council of Research Task Force on Novel Biomarkers and Treatments. (2015). Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. American Journal of Psychiatry, 172(10), 950-966. 7) Schwartz, J., Murrough, J. W., & Iosifescu, D. V. (2016). Ketamine for treatment-resistant depression: recent developments and clinical applications. Evidence-based mental health, 19(2), 35.

Dissociation and Psychotomimetics Effects

It is common to experience dissociation and psychotomimetic effects during IV ketamine administration. These effects are most commonly seen between 40-60 minutes after initiating ketamine infusion and resolved within four hours. The intensity of dissociative symptoms appears to diminish with repeat infusions. Dissociation is more likely with higher doses. The effects are not permanent.1,2,3,4 Anti-anxiety mediation is on hand should these symptoms negatively affect your treatment.  

Cardiovascular

Chest pain, palpitations, and/or pressure may occur which generally resolve within 90 minutes.1

Changes in blood pressure are common.  Within 40 minutes of treatment, systolic blood pressure may rise between 8 to 19 mmHg while diastolic blood pressure may rise 13 mmHg.  These changes tend to resolve within 4 hours of onset.  Higher doses increase the likelihood of changes in blood pressure.  We monitor your pulse and blood pressure throughout treatment and have medication on hand to lower your blood pressure if becomes clinically concerning.

Other side effects include anxiety, blurred vision, dizziness, headache, nausea and vomiting.2,7

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What are dissociative and psychomimetic effects of ketamine?

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”. 

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How do you manage the side effects of ketamine 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.  

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. 

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. 

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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. 

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.  

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.

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.”

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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 individuals concluded that "IV ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression."1

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.

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. 

I would personally try esketamine (Spravato) before IV ketamine because of the reduced risk of side effects and decrease abuse potential.  

Can I die from Ketamine?

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!  Ketamine, 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.

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.

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

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 ketamine in office.  We do not send you home with ketamine.  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.   

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