S-Ketamine – What’s That?


 

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W-H-A-T’s  T-H-A-T?

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S-Ketamine nasal spray is undergoing clinical trials in a few countries in Europe for treatment of Major Depressive Disorder. It may have fewer side effects and be effective at a lower dose than the FDA approved racemic ketamine we now have in the U.S.

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Racemic means it has equal amounts of left-and right-handed enantiomers of a chiral molecule. Google those words if you wish, or just look at your left and right hand. They are not the same. That’s the point, and that’s why FDA must approve new clinical studies on S-Ketamine nasal spray which, I understand, is being fast-tracked by the FDA for Treatment Resistant Depression.

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S-ketamine has twice the affinity for the NMDA receptor (compared to racemic), it’s a 4-times more potent dopamine re-uptake inhibitor, and there’s quicker elimination from body too. However, it still may have a hallucinogenic effect related to enhanced glucose metabolism in prefrontal cortex . . . . But not due to effect on sigma receptors, because it doesn’t have much affinity for those; and it may still elevate liver enzymes.

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I will be very interested if that’s true of liver enzymes. It is extremely rare in my experience.

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I am told that Thomas Insel, MD, the Director of the National Institute of Mental Health, NIMH, says ketamine is the most important new drug in psychiatry.

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I hope my patients could feel that level of support from their local treating doctors. In my experience it is one of the safest medications I have prescribed in 40 years of medicine. I saw patients with intractable status epilepticus, chronic pain, cancer pain and treatment resistant depression. There is simply nothing comparable to ketamine. These conditions can be highly refractory.

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Further, Dr. Insel “Acknowledges That Antipsychotics May Worsen Long-Term Outcomes.” I have seen psychiatrists who prescribe antipsychotics all their lives, now discharge patients now normal on ketamine at long last after decades of treatment resistant depression that has ruined their lives, their finances and their families.

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Why? Because it works? Because it’s generic and there are no drug representatives who come every week to offer free dinners? I hate to think that but the wall of resistance is awful for these patients.

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I am deeply concerned that S-ketamine nasal spray

may be allowed only

for use in Emergency Departments.

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That means the dose will

likely not be individualized.

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It should be made available not just for Emergency Departments but also for outpatient use to physicians specially trained in the simple technique of how to start low, go slow, as we do in medicine to find an effective dose with fewest side effects. We have taught that at UCLA Epilepsy Center since the early 1980’s. And we use ketamine IV for Status Epilepticus – it works in emergency when nothing else works, and it’s a lot safer than many other drugs that induce coma: No effect on breathing. Of course, we are not inducing coma for depression or pain. We only use high-dose ketamine to do that for anesthesia in the Operating Room or for Status Epilepticus in the ICU. It is wonderful for pain when all else fails, including continuous infusion for cancer pain or Complex Regional Pain Syndrome.

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Outside of emergencies, start low, go slow works for ketamine as well as it does for epilepsy medication and for strong opioids like fentanyl spray for rapid changes in cancer pain.

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Going fast in high dose increases the potential for injury, even dreaded side effects or death. Yes, in an emergency we may consider the use if benefit exceeds the risk. That is best done in special facilities or ICU. The Benefit: Ketamine may allow suicidal ideation to resolve in ten minutes. But if the untrained ER doctor gives a high dose in a big man who needs a tiny dose – and yes, I have large male patients who respond to tiny doses – why give an unnecessarily high-dose to a person who has already suffered black suicidal thoughts that very night and almost killed him or herself?

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When you start low, go slow, one does not need to rush for suicidality to be gone in minutes. We can wait 1 or 2 days if need be. But it can still resolve in 10 minutes in some, and at most one or two days in almost everyone. Breathe . . . . . . . easy. . . . . . like new life, a return of life, dawning.

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I’ve seen cancer patients who had such severe hallucinations from Narcan that instantly reversed their opioid, slamming their body into acute withdrawal, that they literally saw the devil. They would never go near drug that again if in their power. Trembling fear. That could potentially happen with ketamine when given in a dose too high, the “one formula fits all.”

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Hallucinations: The other day I saw a patient who had a history of hallucinations with Lyrica, Cymbalta, and now with ketamine after he slowly increased the dose to a non-effective low dose of 20 mg. He vividly remembers the hallucination. But his neuropathic pain is so extreme, and he had failed everything else, he was willing to try it again after specific instructions. Hallucinations did not recur. Yes, there is a method: Teach the body how to develop tolerance to the drug and the side effect will not continue; now you are able to push the dose to the effective level for depression or, in far higher doses, for neuropathic pain.

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Persons with Major Depressive Disorder

respond to

far lower doses of ketamine

than persons with severe neuropathic pain.

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Ketamine is unique for its rapid onset relief, and, when it is administered in an individualized way, it has fewer side effects. Many physicians and lay persons are likely afraid of rare side effects, and they may shun this valuable drug. Even now, everyone is started with the same sudden high IV dose: BHAM a big dose! Thus, when S-ketamine is FDA approved for use in a nasal spray the need to limit that method to emergency settings is very reasonable: the high dose BHAM! for S-ketamine spray in Emergency. Ketamine can be rapidly effective.

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But for chronic severe forms of Major Depressive Disorder when there is no sudden emergency, I know of no better way to teach the use of ketamine nasal spray than we do now when we teach the use of rapid onset fentanyl spray under tongue. Simply teach how to begin treatment, slowly, at home, to reach the effect in one or two days.

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I urge the FDA approve home use of S-ketamine for chronic conditions. There is very little difference between the use of rapid onset fentanyl spray under tongue for severe cancer pain and the use of ketamine nasal spray. I teach that to patients and doctors. It is humane and easily within our reach to address intolerable suffering.

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With use of medication at home rather than Emergency Room, the patient is given control of a chronic intractable condition that fails to respond to other remedies. As always, physicians must assess past records and the entire history, the risk of addiction and drug abuse, and follow the patient at reasonable intervals for potential toxicity.

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The main difference between ketamine and high dose opioids is that ketamine does not affect breathing, whereas we know what does, and its making headlines: death from prescription opioids. Any drug could potentially cause death, that’s why we use utmost caution and best judgement. Read about all the street addicts you want, and the sad thing is ketamine is now the #1 drug of abuse in China, but how different is that from opioids even on our streets? Yet, if you had an intractable condition, name the top drugs you would want to take home with you.

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Here I discussed more about my experience with the drug for Treatment Resistant Depression.

 

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PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
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Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor.
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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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