Simply Calming


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First, an introduction or just skip below to web link, below, of the sweet Suzuki Roshi breathing practice of exhalation. It is so simple people with Alzheimer’s can do it. So instantly calming.

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It is best to practice while we are young and build a solid practice, make it part of being with your Self. The Divine Self. It is so simple and so sweet. It is who we are.

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A wonderful practice and highest teaching. We are all the divine essence, the serene soul. Enjoy how simple and calming…..relax and be in the moment of which the highest teachings speak, as far back as the Vedas and Upanishads, Buddha and all spiritual traditions have taught. 

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There is no god but God. There are no other gods. Not dreamy woo woo stuff. It just Is. Omnipresent. 

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“This is no world. It is God Himself. In delusion we call it world.” Vivekananda (6:371) “Complete self-surrender is the only way to spiritual illumination. Vivekananda (5:258)

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Acceptance. Enjoy who you already are. 

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Just be. You are That. We forget our true self. This is real. No kids play. 

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We all experience these moments. Being. Just being. Simple as breathing. 

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“ There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

 

The Upanishads describe that stage as turiya pure consciousness. Turiya is the background that underlies and transcends the three common states of consciousness.

Buddhists call this emptiness. Advaita calls it fullness. The Divine Essence. God. The self that merges into the Absolute beyond, time space and causation Beyond name and form there is nothing else but the Self, Existence-Consciousness-Bliss. And this pure simple breathing out brings it into this very moment.

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from the dharma message of Zen priest and teacher White Lotus Judith Ragir.

click above name to go directly to the website for this  dharma teaching – it will be easier to read. 

 

Exhaling and dissolving.

Here are some quotes from Suzuki Roshi in “Not Always So” (chapter: Calmness of Mind) that emphasize working with the exhale while meditating:

Calmness of mind is beyond the end of your exhalation. If you exhale smoothly, without even trying to exhale, you are entering into the complete perfect calmness of your mind. You do not exist anymore. 

Inhaling without effort you naturally come back to yourself with some color or form. Exhaling, you gradually fade into emptiness – empty, white paper. That is shikantaza. The important point is your exhalation. Instead of trying to feel yourself as you inhale, fade into emptiness as you exhale. 

To take care of the exhalation is very important. To die is more important than trying to be alive. When we always try to be alive, we have trouble. Rather than trying to be alive or active, if we can be calm and die or fade away into emptiness, then naturally we will be all right. Buddha will take care of us. Because we have lost our mother’s bosom, we do not feel like her child anymore. Yet fading away into emptiness can feel like being at our mother’s bosom, and we will feel as though she will take care of us. Moment after moment, do not lose this practice of shikantaza.” 

This is very impressive quote to me. It is in alignment with the fourth Tetrad of the Anapanasati Sutra. The Anapanasati Sutra is composed of sixteen contemplations, which divide rather neatly into four sets of four: The body group, the feelings group, the mind group, and the wisdom group. They are in a “somewhat” developmental order in that mindfulness of the physical movements of the breath is the first emphasis in any concentration practice. The feelings group is ***becoming sensitive to rapture and joy in meditation***and then calming or letting go of rapture. The third group is the mind group – becoming aware of the mind, gladdening the mind, steadying the mind, and liberating the mind. (See “Breath by Breath” by Larry Rosenberg. This is a book Clouds in Water studied several years ago).

The fourth group the wisdom group is very similar to Suzuki Roshi’s quote above.

From a Thich Nhat Hanh translation:

13. I am breathing in and observing the impermanent nature of all dharmas. I am breathing out and observing the impermanent nature of all dharmas. He practices like this.

14. I am breathing in and observing the fading of all dharmas. I am breathing out and observing the fading of all dharmas. She practices like this.

15. I am breathing in and observing liberation (cessation). I am breathing out and observing liberation (cessation). He practices like this.

16. I am breathing in and observing letting go (relinquishment). I am breathing out and observing letting go (relinquishment). She practices like this.

This sutra demonstrates how the breath can take you all the way to the deepest realizations. The breath often is used as the first object of concentration. But it also can practiced as a complete teaching which leads to insight.

In Larry Rosenberg’s book, he writes about Buddhadasa’s approach to breath practice and its use for going all the way to realization. He writes:

“ When we got to the thirteenth contemplation – which concerns impermanence, this is where real vipassana begins – he said that Anapanasati was one of the simplest and most effective means for realizing emptiness.” 

Buddhadasa said: “There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

Perhaps this is where Zen and Vipassana meet. Where the Mahayana and the Theravada come to the same conclusion.

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.http://www.judithragir.org/2014/01/exhaling-and-dissolving/

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Cannabidiol (CBD) FDA Approved for Epilepsy – May Help Pain, Mood – Costs Review


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Epidiolex from GW Pharmaceuticals, is a cannabidiol (CBD) recently approved by FDA for treatment of epilepsy. Others have found CBD helpful for pain, migraine, and mood disorders. CBD is one of the more than 80 known cannabinoids in the cannabis plant, the marijuana plant. It has no psychoactive effect, that means it does not make anyone “high”. But urine drug tests will be positive for marijuana and anyone may risk losing their job if their employer checks – some drug tests do not specify marijuana.

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Medications can be prescribed off-label by your doctor for conditions other than the FDA approved epilepsy in this case, and hopefully covered by healthcare insurance. Below are costs of the Epidiolex brand reviewed by O’Shaughnessy’s newsletter, the newsletter originally for California cannabis doctors.

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FDA approval means CBD now has accepted medical use and should be no longer classified as Schedule I, though the ruse will likely be continued by congress.

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GW Pharmaceuticals PLC said it plans to charge about $32,500 per patient annually in the U.S. for its new treatment for rare forms of epilepsy, the first prescription drug derived from the marijuana plant.

Chief Executive Justin Gover said in an interview Wednesday that the company set the price to be in line with other brand-name epilepsy drugs, such as H. Lundbeck A/S’s Onfi. He noted that the FDA designated the product an “orphan drug,” meaning it treats rare conditions, and that some other orphan drugs carry higher prices.

Out-of-pocket costs for patients taking Epidiolex could range from $5 to $10 a month for those in state Medicaid programs to as high as $200 a month for some private insurance plans, Julian Gangolli, president of the company’s North America unit, said on a conference call with analysts Tuesday. Uninsured patients may qualify for receiving the drug free.

Dr. Jacqueline French, chief scientific officer of the Epilepsy Foundation, said there are low-cost generic epilepsy drugs on the market, but many patients with the rare forms of the disease have already tried them and the drugs didn’t help much.

Dr. French said Epidiolex improved symptoms for many children in clinical trials, and she is happy the price isn’t significantly higher.

The company expects to make the drug available after the U.S. Drug Enforcement Administration assigns it a controlled-substance classification, a decision expected by late September. GW Pharmaceuticals will distribute the drug through specialty pharmacies that ship directly to patients and caregivers.

FDA approval of a CBD extract means that cannabidiol now has an acknowledged medical use and therefore doesn’t fit a key criterion of Schedule I status. DEA rescheduling is supposed to follow as day follows night. Logically, the DEA resked should apply to cannabidiol, the molecule. But fixisin.com says CBD will remain on Sked I, with an exception created for CBD in an FDA-approved pharmaceutical.”

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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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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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

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Please IGNORE THE ADS BELOW. They are not from me.

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Ketamine for Bipolar Disorder Fear of Harm Phenotype Saved This Man’s Life


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Ketamine has given life back to so many who have been disabled by treatment resistant depression, bipolar disorder or intractable pain. It was approved in 1970 as an injectable anesthetic. It can be prescribed off-label from a compounding pharmacy inexpensively as a nasal spray or sublingual liquid or sublingual tablet for outpatient use or it may be given I.V. in a clinical setting. A patented nasal spray may be available soon (see below) for use only in a clinical setting.

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For many posts on ketamine since May 2009, use search function within this site at top left above small photo.

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NPR Morning Edition news today on ketamine for bipolar disorder “fear of harm phenotype.”

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For six years now, life has been really good for James. He has a great job as the creative director of an advertising firm in New York City. He enjoys spending time with his wife and kids.

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And it has all been possible, he says, because for the past six years he has been taking a drug called ketamine.

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Before ketamine, James was unable to work or focus his thoughts. His mind was filled with violent images. And his mood could go from ebullient to dark in a matter of minutes.

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Ketamine “helped me get my life back,” says James….

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…pharmaceutical companies are testing several new ketamine-related drugs to treat depression. Johnson & Johnson expects to seek approval for its nasal spray esketamine later this year, though the approval would be limited to use in a clinical setting.

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Meanwhile, doctors have begun trying ketamine on patients with a wide range of psychiatric disorders other than depression. And there is now growing evidence it can help people with anxiety, bipolar disorder, post-traumatic stress disorder, and perhaps even obsessive-compulsive disorder.

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“I think it’s actually one of the biggest advances in psychiatry in a very long time,” says Dr. Martin Teicher, an associate professor of psychiatry at Harvard Medical School and director of the Developmental Biopsychiatry Research Program at McLean Hospital.

James found his way to Dr. Demitri Papolos, an associate professor of clinical psychiatry at Albert Einstein College of Medicine.

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“He was like a whirling dervish when he came into my office,” Papolos says. “He was extremely fearful and scanning the environment all the time and he overheated at the drop of a hat.”

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Papolos diagnosed James with a variant of bipolar disorder he calls the “fear of harm phenotype.” It typically appears in childhood and often doesn’t respond to traditional psychiatric drugs.

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But Papolos has found that the condition does respond to ketamine. “It’s been transformational,” he says.

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In January, Papolos published a study of 45 children with the problem. They inhaled a nasal mist containing ketamine about twice a week. Nearly all got dramatically better.

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Scientists still aren’t sure why ketamine works, but there’s evidence that it encourages the brain to rewire, to alter the connections between cells. That process has been linked to recovery from depression. And it may also explain why ketamine helps people who have symptoms associated with several different psychiatric disorders.

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“I think it’s having multiple effects, and that means it’s probably useful for multiple different disorders,” Teicher says.

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One of those effects involves a part of the brain involved in temperature regulation. And that could explain why patients like James usually stop overheating once they are taking ketamine.

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James started taking a ketamine nasal spray every other day. He says his response was dramatic….

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Ketamine Relieves Depression By Restoring Brain Connections

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NPR All Things Considered published on ketamine 3/20/2017:

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Ketamine For Severe Depression: ‘How Do You Not Offer This Drug To People?’

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Gerard Sanacora, a professor of psychiatry at Yale University, has treated hundreds of severely depressed patients with low doses of ketamine, an anesthetic and popular club drug that isn’t approved for depression.

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“If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they’ve tried the standard treatments, how do you not offer this treatment?” he says.

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Why insist someone be suicidal? How do you not offer it to people who have failed all treatments and are disabled by intractable pain or treatment resistant depression? 

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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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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  

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Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Oxytocin for Pain, Treatment Resistant Depression and Bipolar Disorder


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Recent publications on Oxytocin are listed below. It is a very effective hormone made by the brain. It is NOT the opioid oxycodone and NOT oxycontin.

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Use search function top left above photo to see previous postings on oxytocin since 2013. It can be extremely important in the treatment of intractable pain, treatment resistant depression, bipolar disorder or anxiety.

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Once you titrate to the proper dose for each person —from 10 to 100 u’s, relief is quite astonishing, with rapid onset in a few minutes when given under the tongue – only after reaching that person’s dose, simple, without side effects. May use as needed 3 or 4 times per day. There is no withdrawal.

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Avoid use if polycystic ovary syndrome (PCOS). 

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Oxytocin must be made by a compounding pharmacy. Healthcare insurance refuses to reimburse for any compounded medications though they are far less expensive even than gabapentin that fails to help so many with pain, and oxytocin is far more effective. 

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Every time you hug someone, you are giving each other oxytocin. When your dog and you stare at each other, oxytocin is being stimulated. Having discussed that with one of my patients, he came back one month later to say he and his wife had fallen in love again after almost 50 years of marriage because they’ve been hugging every day: hugs stimulate oxytocin. 

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Behavioral effects of oxytocin are highly context- and person-dependent. You are not going to fall in love with someone you do not like. 

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Rash, JA, et al: Oxytocin & Pain, A Systematic Review & Synthesis of Findings. Clin J Pain 30(5):453-462, May 2014.

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Xin Q et al: The Analgesic Effects of Oxytocin in the Peripheral and Central Nervous System. Neurochemistry Intl 103:57-64, 2017.

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Paloyelis Y et al: The Analgesic Effect of Oxytocin in Humans: A double-blind, placebo-controlled, cross-over study using laser-evoked potentials. 

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MacDonald K, Feifel D. Oxytocin’s role in anxiety: a critical appraisal. Brain Res 2014; 1580: 22–56.

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Churchland PPS, Winkielman P. Modulating social behavior with oxytocin: how does it work? What does it mean? Horm Behav 2012; 61: 392–399.

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Bethlehem, R A I  et al: Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women, Translational Psychiatry, 2017, 7, 4, e1099 ********excellent********

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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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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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

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Please IGNORE THE ADS BELOW. They are not from me.

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Ketamine in Bipolar Depression – A Review


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An excellent review of Ketamine, a rapid-acting antidepressant and anti-suicidal agent, in Bipolar Depression

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Efficacy of Ketamine in Bipolar Depression: Systematic Review and Meta-analysis. 

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Parsaik AK1, Singh B, Khosh-Chashm D, Mascarenhas SS.

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OBJECTIVE: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression.

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METHODS: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis. A random effect model was used to calculate the pooled SMDs. Heterogeneity was assessed using the Cochran Q test and I statistic.

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RESULTS: Of the 721 articles that were screened, 5 studies that enrolled a total of 125 subjects with bipolar depression (mean age, 44.6+/-4.3y and 65.6% females) were included in the systematic review; 3 randomized controlled trials (69 subjects) were included in the meta-analysis. The meta-analysis showed significant improvement in depression among patients receiving a single dose of intravenous ketamine compared with those who received placebo (SMD=-1.01; 95% confidence interval, -1.37, -0.66; P<0.0001). The maximum improvement was observed 40 minutes after the ketamine infusion. No heterogeneity was observed between the studies (Cochran Q test P=0.38, I=0%). The 2 studies that were excluded from the meta-analysis also showed significant improvement in depression after ketamine therapy. Individual studies also reported improvement in anhedonia and suicidal ideation after ketamine therapy. None of the subjects had serious side effects, and the side effects were similar between the ketamine and placebo groups.

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CONCLUSIONS: This study suggests that ketamine is effective in treatment-resistant bipolar depression and may reduce suicidal ideation and anhedonia.

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The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

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

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The advertising below is not recommended by me.

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Ketamine Prescribed Since 1994 – My Experience


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Ketamine offers an opportunity for normal life unmatched by any medication I know of when given off-label for chronic treatment of intractable pain, treatment resistant depression, bipolar depression, juvenile bipolar disorder. It is one of the safest medications I have prescribed in 41 years of medicine. I have never seen anything more effective – it is not a cure, but remission is highly possible. Please refer to peer reviewed references since 2009 on this website on ketamine and depression or pain. Read elsewhere about street drugs, junkies, addicts and media headlines.

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Never Ketamine Alone

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Ketamine is short acting no matter how it is given.

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I never prescribe ketamine by itself – a fools errand; the religion of ketamine is like the religion of opioids. Decades of intractable conditions and chronic neuroinflammation require more than one short acting drug and usually require a multi-disciplinary approach. I work with psychologists or psychiatrists and other specialists when indicated.

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Entourage effect 

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DRUGS ARE LIKE POLITICIANS. A FAMOUS POLITICIAN MAY WALK UNRECOGNIZED, BUT WHEN YOU SURROUND HIM OR HER
WITH MANY PEOPLE, EVEN OF LESSER STATUS, THE POLITICIAN HAS A FAR MORE POWERFUL EFFECT.

Mechoulam

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1994 – I first prescribed IV when teaching cancer pain at MD Anderson Cancer Center.

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2001 – prescribed for outpatient care of chronic intractable pain

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2011 – prescribed for treatment resistant depression, bipolar depressed, juvenile bipolar/fear of harm phenotype often diagnosed as oppositional defiant disorder.

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2009 – writing about ketamine, neuro-inflammation and glial modulators on this site, with classic references to publications from the foremost peer reviewed journals, including low dose naltrexone, oxytocin.

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Dosing

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Depression, Bipolar Disorder, Juvenile Bipolar/FOH, treatment resistant – may need a dose only twice daily or every 3 days. The dose and frequency of use cannot be predicted – it is idiosyncratic – look up that word.

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Intractable pain – dosing and frequency of medications is very different than for depression.

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My work with these medications, these glial modulators, is too extensive to annotate on these pages. This website since April 2009 has references for context and guidance with active links to peer reviewed publications. Example:

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Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. D Papolos et al, J Affect Disord. 2013 May;147(1-3):431-6.

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RESULTS:

Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

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CONCLUSIONS:

Intranasal ketamine administration in treatment-resistant youth with BD-FOH produced marked improvement in all symptomatic dimensions. A rapid, substantial therapeutic response, with only minimal side effects was observed. Formal clinical trials to assess safety and efficacy are warranted.

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mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. R Duman et al, August 2010, Science, Science 2010 Aug: Vol. 329, Issue 5994, pp. 959- 964. [this article free with registration]
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ABSTRACT:

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We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.

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“The resulting protein synthesis and neuronal alterations in the medial prefrontal cortex are the opposite of those produced by chronic stress….”

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Read elsewhere about street drugs, junkies, addicts and media headlines.

If that is you, see an addictionologist, not me.

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Some medications can be drugs of abuse but every patient and every medication that I dispense is followed meticulously. If any sign of misuse or abuse, that unfortunate person is immediately discharged and referred elsewhere.

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For my Home Page, click here: 

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Welcome to my Weblog on Pain Management!

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This site is not for email or medical advice.

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It is not legal for me to give medical advice

unless you are my patient which means I have done a medical history and examination.

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I generally accept only those who have failed most or all known treatments, and only those who I feel I can help.

 

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I interview each patient before accepting.

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Any advertising below is not recommended or condoned by me.

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Be the change you wish to see – or walk away. Money at NIH


 

 

A Turning Point

 

$$$$$ MONEY $$$$$

 

at NIH

 

May not come this way again

 

NIH developing

5-year NIH-wide Strategic Plan

 

 

 

Donate to organizations, below

They can provide feedback to NIH via the

RFI Submission site


 

 

 

John C. Liebeskind, 1935 – 1997, distinguished scholar and researcher, past president of the American Pain Society, had the radical idea that pain can affect your health.

 

Research decades ago by an Israeli team at UCLA and others had shown “that pain can accelerate the growth of tumors and increase mortality after tumor challenge.” Decades ago Professor Liebeskind lectured all over the country: Pain kills.

 

He wrote an editorial in 1991, summarizing a life’s work:

 

“Pain and stress can inhibit immune function.”

 

 

Quoting John Bonica, the father of modern pain management, he wrote:

 

“Bonica has long argued that the term ‘chronic benign pain’ (used in distinction to pain associated with cancer) is seriously misleading.  Chronic pain is never benign, he contends; “it is a ‘malefic force’ that can devastate its victims’ lives and even lead to suicide.”

 

 

Liebeskind continues, “It appears that the dictum ‘pain does not kill,’ sometimes invoked to justify ignoring pain complaints, may be dangerously wrong.”

 

Pain mediates immune function

 

Importantly

 

  Opioids mediate the suppressive effect of stress on natural killer cells,

 

 published in 1984, immune system.

 

Alcohol increases tumor progression, 1992, immune system.

 

It used to be news.

He did not live to see change.

 

People just want to go on doing what they’re doing.

They want business as usual.

 

 

After 1991, we saw the great discoveries of neuroinflammation, pioneered by Linda Watkins, PhD, the early understanding of the innate immune system, its involvement in chronic pain and depression, and a few weeks ago, a British team showed neuroinflammation in teens with early signs of schizophrenia and DNA markers.

 

 

Major Depression has the same neuro-inflammation found in chronic pain, often responding to same medications, in particular glial modulators – immune modulators. Now, perhaps early schizophrenia will respond to glial modulators, reducing inflammation seen on scan in teens, before they become homeless and burned out by antipsychotic drugs

 

Inflammation out of control destroys neurons

 

Fire on the brain

 

 

We must be the change we wish to see

 

It’s not just the Bern. It’s been starting. Forces are finally coming together. We want change. It’s been too much. Too long.

 

We won’t take it anymore.

 

I figure if I tell you about it, you might just mention it to someone to pass it on. That is all. One small action may lead to change. Activate inputs to the NIH strategic plan.

 

 

~ Action needed ~

 

Prices of drugs becoming unaffordable

No new drugs for pain or major depression

Research to repurpose existing drugs

Expose the politics destroying our compounding pharmacies

 

Above all

The #1

Major Priority:

Request NIH to solicit priority call for research on

Glial modulators of the

Innate immune system

 

 

Why?

 

Glia modulate

chronic pain, major depression

and almost every known disease

 

Glia are your innate immune system

 

Inflammation kills

 

 

 

 Stress kills. Inflammation kills.

 

 

Pain kills

 

In the 1970’s, Professor Liebeskind and an Israeli team at UCLA injected cancer cells to two groups of rats that had sham surgery. Cancer spread much faster and killed far sooner in the group with poor treatment of surgical pain.

 

 

~ Pain kills ~

 

He lectured all over the country

 

Forty five years ago

 

 

I’m gonna be dead before I see this country do anything but unaffordable opioids and the magical ineffective trio of gabapentin, Lyrica, Cymbalta to treat chronic pain. The devastating, blind, nationwide emphasis does nothing to address the cause: inflammation, the innate immune system gone wild.


 

 

Innate immune system in action

 

Untreated pain suppresses the hormone systems too.

 

Untreated depression – same inflammation kills lives.

 

Where’s the money?

 

We are the change we wish to see. It’s pitiful I am so lazy. Suddenly, too late, we may need something, but, aha, no new drugs in the pipeline.

 

 

 

~ Make a joyful cry to NIH ~

 

They are soliciting input from professional societies

 

If your condition has failed all known drugs for pain or major depression, then make a joyful cry to NIH, now, before they give away all that nice new $$$$$money$$$$$.

 

 

Follow and join

 

American Pain Society

 

 

International Association for Pain

celebrating 40 years of pain research

 

 

Reflex Sympathetic Dystrophy Syndrome Association

help for CRPS/RSD  

 

 

 

The key to CRPS/RSD pain will apply to all forms of chronic pain, in particular the most difficult form, neuropathic pain. RSDSA funds research into all forms of chronic pain, not only Complex Regional Pain Syndrome (CRPS/RSD). Their scientific board members are not funded by opioid money.

 

 

 

Exactly

what is the annual cost of care

as fraction of GDP

for the growing population of Americans on opioids

for one year, for lifetime?

 

 

People are dying from prescription opioids and those who need them find they don’t work well enough. Prescriptions opioid costs must be a huge fraction of the medical costs in the United States GDP. You are required  to see a doctor every single month each year, often lifelong, just for one opioid, 12 months a year x 30 years x tens of millions of people and increasing – a growth industry. Not even counting $600 a day for the opioid, what the cost of monthly visits for 30 years? Not counting the army of DEA, FDA, CDC agents watching the opioids like a hawk. We all have to be sharp, addiction is growing. Addiction aside, deaths from prescription opioids are shaking up the CDC forcing urgent change this coming month.

 

 

 

Opioids do not work well for chronic pain

We need better

It’s not just the $600/day price

They just don’t work

 

 

donate

 

 

Raise a joyful noise at NIH now or write back at us readers with comments and better suggestions. Tell others what you’d like to see. Which politicians do you know would be most interested in this at national levels and organizations?

 

You may never see this change unless you do it now. Other forces will get this new money.

 

 

Turning point now

May not return

 

 

We are at a turning point and we will fail to catch the sail that’s coming fast to carry all research money in their shiny big stem cell direction. They never look back.

 

 

There is so many medications we can use today, FDA approved drugs that can be re-purposed and applied to recent cutting edge science. Someone must pay to do the work to study this.

 

 

Re-purpose old drugs

 

 

Stanford just showed a popular generic drug improved recovery of stroke paralysis in mice to begin at 3 days rather than 30. Old drug, new purpose, of course more years of testing to confirm in humans. Brilliant team applying new science.

 

 

Request
NIH to solicit a

Special Invitation

for 30 good protocols to

repurpose old drugs

 

 

Hundreds of old drugs, already approved, could be involved in mechanisms we have recently learned about. Speak up or money will go to shiny new stem cells. None for chronic pain or major depression. No company will find this profitable – it must be funded by NIH. A popular generic sleeping pill can bring astonishing return from stroke paralysis.

 

 

Congress has not opened this new money to NIH in many long years. How often will there be extra money?

 

 

donate

 

 

Lawrence A. Tabak, D.D.S., Ph.D.
Principal Deputy Director, NIH, solicits you to

Review the NIH Strategic Initiative Plan and their

Request for Information (RFI) and the NIH website

and provide your feedback via the RFI Submission site

 

 

This is for “stakeholder organizations (e.g., patient advocacy groups, professional societies) to submit a single response reflective of the views of the organization/membership as a whole. We also will be hosting webinars to gather additional input. These webinars will be held in early to mid-August.

 

 

 

Be the change you wish to see

Donate to those organizations

to solicit the change you wish to be

 

 

 

Happy New Year

Rejoice!

There’s money at NIH

 

 

 

 

 

 

The material on this site is for informational purposes only.

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

Relevant comments are welcome.

If any questions, please schedule an appointment with my office.

This site is not for email.

~~~~~

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

 

 

 

 

Analgesic Response to Ketamine Linked to Circulating microRNA in Complex Regional Pain Syndrome


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Analgesic Response to Intravenous Ketamine

Is Linked to a Circulating microRNA Signature

in Female Patients

With Complex Regional Pain Syndrome

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The ability to measure Micro RNS’s (miRNA) in blood looks like it may become an important tool someday once it is available for the clinic. It could be used to predict if your condition will respond to various medications.

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MicroRNAs are emerging as important modulators of various psychiatric (schizophrenia, bipolar disorder) and neurological conditions including pain, epilepsy, cognitive dysfunction, neuronal development, structure and function. “MicroRNAs are small, non-coding RNAs that act as post-transcriptional regulators of gene expression.  miRNA’s can be affected by morphine and affected by other drugs. It is hoped that complex clinical phenotypes may be profiled in assays of peripheral blood and may predict response to treatment such as in this study. Ketamine is given for selected patients that have failed to respond to standard treatment.

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This research was published in Pain, June 2015, by Professor Schwartzman’s group at Drexel University. Seven of his patients with Complex Regional Pain Syndrome were ketamine responders and 6 were poor responders. They note that, “Although [ketamine] treatment is generally effective, approximately 30% of patients have an inadequate response to ketamine.”

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“Stability in circulation and dysregulation in disease state are 2 features making extracellular miRNAs useful candidates for biomarker discovery. Alterations in miRNA profiles have been reported for rheumatoid arthritis and systemic lupus erythematosus as well as for painful conditions such as irritable bowel syndrome, chronic bladder syndrome, endometriosis, and migraine. Cerebrospinal fluid from patients with fibromyalgia showed differential expression of 9 miRNAs.”

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Quoting directly from the article:

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Highlights

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•We studied ketamine treatment–induced miRNA alterations in blood from patients with CRPS.
•Differential miRNA expression was observed in whole blood before and after treatment.
•Before therapy, 33 miRNAs differed between responders and poor responders.
•Lower pretreatment levels of miR-548d-5p may contribute to higher UDP-GT activity.
•Circulating miRNAs can be potential biomarkers in predicting treatment response.

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From the Abstract

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Investigation of the mechanistic significance of hsa-miR-548d-5p downregulation in poor responders showed that this miRNA can downregulate UDP-glucuronosyltransferase UGT1A1 mRNA. Poor responders had a higher conjugated/unconjugated bilirubin ratio, indicating increased UGT1A1 activity. We propose that lower pretreatment levels of miR-548d-5p may result in higher UDP-GT activity, leading to higher levels of inactive glucuronide conjugates, thereby minimizing the therapeutic efficacy of ketamine in poor responders.

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Perspective

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This study suggests the usefulness of circulating miRNAs as potential biomarkers. Assessing miRNA signatures before and after treatment demonstrated miRNA alterations from therapy; differences in miRNA signature in responders and poor responders before therapy indicate prognostic value. Mechanistic studies on altered miRNAs can provide new insights on disease.

 

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From the Discussion

.

Ketamine is also considered to be the prototype for a new generation of glutamate- based antidepressants that can alleviate depression within hours of treatment. Several biological measures have been explored to characterize treatment response and to gain insight into mechanisms underlying the rapid antidepressant effects of ketamine. A plasma metabolomics study in patients with bipolar depression suggested that the basal mitochondrial b-oxidation of fatty acids differed between responders and nonresponders to ketamine. Other studies have shown differences in baseline plasma concentrations of D-serine, serum levels of interleukin 6, and plasma levels of Shank3, a postsynaptic density protein involved in NMDA receptor tethering and dendritic spine rearrangement.

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Differences in the ability to metabolize ketamine because of interindividual differences and pharmacogenetic factors have been proposed to contribute to the varied responses to ketamine therapy and its clinical outcome. Similar conclusions have been drawn for patients with depression; plasma from patients with treatment- resistant bipolar depression who had undergone a single 40-minute infusion of a subanesthetic dose of ketamine showed that although NK is an initial metabolite, it is not the major circulating metabolite. This again suggests that other downstream metabolites of ketamine may play a role in the pharmacological effects of the drug. It is also known that (2S,6S)-hydroxynorketamine is an active and selective inhibitor of the a7 subtype of the nicotinic acetylcholine receptor; this activity was shown to contribute to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. We postulate that in patients with CRPS, 1 factor contributing to resistance is an altered pharmacokinetic profile produced by enhanced elimination of active metabolites downstream of NK, which is mediated by hsa-miR-548d-5p. However, because we have relied on indirect evidence of a higher percentage of direct/indirect bilirubin in poor responders, indicating increased UDP-GT enzyme activity, additional studies investigating hydroxynorketamine and its downstream metabolites along with their glucuronide conjugates in plasma and urine will provide direct evidence for the role of miR-548d-5p in mediating response to ketamine therapy in responders and poor responders.

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They noted a significant difference in body weight between responders and nonresponders (heavier), but not in duration of disease and analgesic response to ketamine. Toward that end, they will publish separately upon

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… investigating the link between miR-34a, which showed 28-fold reduction in poor responders relative to responders (Table 2), and the neuroendocrine system….

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From the Conclusion

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Our studies showed that miR-548d-5p can regulate UDP-GT but not CYP3A4, suggesting that UDP-GT activity in responders and poor responders may be mediated by differences in the level of circulating miR-548d-5p. Lower levels of miR-548d-5p in poor responders before treatment could result in higher UDP-GT activity, leading to the production of more inactive glucuronide conjugates and faster elimination of active ketamine metabolites downstream of NK. Thus, the levels of hsa-miR-548d-5p could minimize the therapeutic efficacy of ketamine and pain relief. Differences in miRNA signature can thus provide molecular insights distinguishing responders from poor responders. High failure rates of drugs targeted to treat neuropathic pain warrant changes in approaches. Studies targeting well-defined patient populations for clinical trials will play a crucial in developing drugs that may be efficacious in a subset of patients. Extending this approach to other treatment and outcome assessments might permit stratification of patients for maximal therapeutic outcome.

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How frustrating it is for patients and family who must cope with an intractable condition such as pain or Bipolar Disorder or treatment resistant Major Depression that has failed all commonly prescribed medications. For all of them, we need changes in approach.

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“High failure rates of drugs targeted

to treat neuropathic pain

warrant changes in approaches.”

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Perhaps scientists reading this would comment upon how it may relate to tolerance as it differentially occurs in those receiving intermittent ketamine vs continuous intravenous infusion.

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Dysregulation of miRNA’s has been shown in psychiatric disorders including depression and schozophrenia, neurodevelopmental disorders, cognitive dysfunction,  epilepsy, chronic pain states with implication for the cause and treatment of these disorders.

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Research targeting miRNA’s as novel treatment for depression has shown that chronic fluoxetine, repeated electroconvulsive shock therapy, and acute ketamine have the capacity to alter hippocampal miRNA levels.

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It is hoped these tests may be available someday clinically as the cost of off-label treatment not covered by insurance is a great burden for those already disabled by intractable pain or treatment resistant depression.

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PUBLIC WARNING

warning reprinted with permission of Demitri Papolos, MD
.
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.
.
It is not legal for me to provide medical advice without an examination.

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

~~
This site is not for email and not for appointments.

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

~~~~~

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

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Please ignore the ads below. They are not from me.

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Intranasal Ketamine in Major Depressive Disorder


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Physicians at Icahn School of Medicine at Mount Sinai, New York, studied intranasal ketamine in 18 patients with Major Depressive Disorder, published in 2014:

.

A Randomized Controlled Trial of

Intranasal Ketamine in Major Depressive Disorder

.


Conclusions

.

“This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.”

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I have previously posted more detail on this study. They report a significant antidepressant effect occurred as early as 40 minutes in some. I have seen some respond in seconds. But the dose is unique and specific to each person and there is no response until that dose is reached.

.

~~~

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It is hoped that more studies will be funded, though that seems unlikely since congress slashed the NIH budget in 2010 by the unthinkable 30%, never done in history.

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Entire generations of scientists are now lost forever.

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Ketamine Safety

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Ketamine is one of the safest medications I have prescribed in 40 years of medicine. And I meticulously obtain laboratory studies at least twice a year to verify any potential harm as it has been reported in addicts that it may affect bladder, kidney, liver or biliary system. I first prescribed ketamine about 14 years ago for intractable pain rated 10 on a scale of 10 for 30 years; and prescribed ketamine since Spring 2012 for Major Depression. For years I searched to find a spray with a metered dosing system. Thus since late 2011, intranasal has been the delivery I find most useful. When given as nasal spray or under the tongue, not swallowed, it goes straight to the bloodstream, bypassing the liver, and works for depression because the liver does not convert it to a different metabolite.

.

Nevertheless, it is important to stress that ketamine must be monitored for any possible adverse effects including toxicity and/or addiction. I require long distance patients to be followed by a psychiatrist or psychologist regularly while on ketamine. So far, my returning patients have been stable for years.

.

Further, when given by the nasal or sublingual route, I do not see the side effects that my anesthesiology colleagues see after I.V. infusion. I’ve been in board meetings with some of the finest anesthsiology pain specialists in the country sharing and comparing experience. I don’t see those complications. But that is what is published and I.V. is how it is given in the few centers where ketamine is used for treatment of Major Depression or Bipolar Depression.

.

Ketamine is a short acting medication whether it is given I.V. or nasally or under the tongue. But it is quite bitter and most prefer nasal delivery.  Review the case study of the professional who traveled out of state once or twice weekly for one year to receive I.V. ketamine. She had failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. She now does very well on a small dose every 48 hours given nasally. In the same post, I reported the patient with Juvenile Bipolar Disorder, Fear of Harm phenotype whose profound thermoregulatory abnormalities respond in seconds to ketamine, with a very small dose of 10 mg nasal spray every 3 days. That’s it! Temperature responds in seconds, and the depression responds in 10 minutes in her case.

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Unfortunately research protocols require the study of fixed dosages in order to be a cost effective study for one sample size at one dose to be even slightly meaningful, even then 18 patients studied at Mt. Sinai is a small study at the one dose they used.

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The principle that I have always used is “start low, go slow.” That allows for the discovery that some large men may require the tiniest dose and some tiny 90 pound seniors may require some of the largest doses I’ve seen. It cannot be predicted by body weight. Anesthesiologists generally think in terms of mg/kg body weight, for example the 0.5 mg/kg I.V. generally used for depression. But ketamine’s dosage variance is unrelated to weight. That likely explains why some develop frightening symptoms when given IV, and others do not respond. One size does not fit all. That method either under-doses or overdoses.

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There are case reports on this website giving examples of some individuals I have seen with Major Depressive Disorder. One man is unusual in needing a small dose only every 6 to 8 weeks, but most use the nasal spray daily or every second or third day. I suspect that after initially starting ketamine on a daily basis for one or two weeks, the frequency of dosing may be lowered to every two or three days. Less is more.

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Professor David Feifel at UCSD guesstimates that ketamine helps 70% of persons with Major Depression. I think that’s a fair statement given that we are unlikely even to see the unknown number who remain at home, forever feeling they are unable to leave their confinement. We know that effects of ketamine are blocked in mice that are deficient in BDNF. We may speculate that when ketamine fails in persons with Major Depression, that may be due to lack of BDNF. We know exercise helps Major Depression and exercise increases BDNF. Much more research is needed.

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The use of ketamine is essentially a first line drug for Complex Regional Pain Syndrome (CRPS). That may never be said in publications, but that has been the case for years in persons with CRPS who have failed all other medications. I specialize in CRPS, a form of neuropathic pain that leads to suicide more often than any other pain syndrome.

.

For pain, intranasal ketamine is far shorter lasting, typically three hours, rarely six. And requires doses far higher than for Major Depression or Bipolar Depression. Even then, when used for pain six times daily in very high doses, it has proven to be profoundly safe with few if any side effects that last less than half an hour, if present at all.

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.

Inflammation

.

The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussed here. The study of ketamine has taken on new life with the discovery that it profoundly lowers pro-inflammatory cytokines produced by microglia. Inflammatory cytokines have been shown to be elevated in chronic pain and in Major Depression. That is why I feel it is important to prescribe adjuncts that also lower inflammatory cytokines. And patients with Major Depression and Bipolar Depression have reported the adjuncts make ketamine stronger and last longer. Some don’t even need ketamine after awhile, but remain on the adjuncts.

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Ketamine is not a cure and I find it is best used with adjunct medication. In my experience, ketamine and adjunct medications are likely to help as long as prior to treatment, patients are still able to function, to work at least somewhat. I do have 4 patients in the last four years who have not left their home or their bed for many years, and they failed to respond. Sadly, one older woman had to be institutionalized for life, her melancholic depression was so deep. When ketamine is even partially effective, I have patients who had been too fatigued to work before treatment, yet who are able to return to graduate school for a PhD and do well for years on a stable dose. It is immensely rewarding to be a part of this unique therapy, to see them regain life and function after years of misery and disability.

 

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.

Studies

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S-Ketamine

.

It is my hope to be able to compare S-ketamine, that is not yet FDA approved, with the racemic* ketamine that we now have, that was FDA approved in 1970 in high dose as an anesthetic. Obviously we do not use high anesthetic doses for control of pain or Major Depression. I understand unfortunately that when clinical studies are completed, S-ketamine will be available only in emergency departments.

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*Racemic means the molecule has equal amounts of left and right-handed enantiomers (mirror images) of a chiral molecule (meaning, you cannot superimpose the left hand with the right hand. They mirror but do not superimpose). Thus both left and right racemic ketamine mixture has been FDA approved, but the S-ketamine, the left sided molecule is considered a different drug, and must be FDA approved.

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Without FDA approval, ketamine can be studied with FDA permission that provides an Investigational New Drug (IND) application.

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Given the lack of funding for almost any research in this country, I would consider doing a patient-funded study if patients showed interest. It would be modeled on the intranasal study published in the Mt. Sinai study, above, i.e. short term, randomized, double blind, placebo controlled.

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It is reported that S-ketamine may be more effective with fewer side effects. This must be proven and cannot be taken at face value without several studies. Shockingly, some publications in recent years have been fabricated and woven into mythology.

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Finally, ketamine is off-label for pain and for major depression.

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Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

..

“Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.”

.

 

.
PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
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.

.

.

.

.

.

.

The material on this site is for informational purposes only.
.
It is not legal for me to provide medical advice without an examination.

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

~~

This site is not for email and not for appointments.

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

 

~~~~~

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

.

Please ignore the ads below. They are not from me.

.

.

.

 

 

Ketamine – small doses work in depression and bipolar disorder


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Everyone is very edgy right now with depression. Media is sensationalizing, which is the worst thing to do. I even hesitate to write this now.

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Ketamine really does work

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Small doses may be all that’s needed. Even large doses are safe.

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Two Cases

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I hate to play on emotion that is strong right now, but Robin Williams might be alive today if his doctors prescribed ketamine nasal spray.

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Every one, doctors and patients alike, worry about ketamine. It sells newspaper headlines and distorted media coverage that then overtakes the life saving stories of its profound safety when used under good medical supervision. Experience helps.

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Two cases from yesterday and today really must be shared. These two patients would not be alive today if they did not have ketamine nasal spray for their depression.

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I don’t mean to say every one will respond to these extremely tiny doses, but it’s always exciting to hear the effective dose is simply so small.

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These details would make good case reports if time permitted, but there is never enough time. I wanted simply to say a few things now because these two patients were seen.

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**1**

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In May 2014, saw a fifty-ish woman who is now responding to 20 mg (4 nasal sprays) given as one dose every 48 hours. She has been treated at well known university psychiatry departments, failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. Received IV ketamine once or twice weekly for one year before I saw her.

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Diagnoses:  dysthymia as long as she can remember, and 25 years of Major Depressive Disorder, PTSD, anxiety, etc. Olympic level athlete —

.

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**2**

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Second patient now in late teens, Juvenile Bipolar Disorder/Fear of Harm phenotype, profound thermoregulatory changes respond in seconds to ketamine, dose of 10 mg nasal spray every 3 days. That’s it! Temperature responds in seconds, and the depression responds in 10 minutes in her case. She was so violent before treatment that she had been hospitalized 7 times in 2-1/2 years. Doing very very well. And the low dose naltrexone, by the way, is involved in thermoregulation.

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I should mention, no side effects whatsoever. I have never seen toxicity. I watch kidney and bladder function meticulously, and patients with massive pain on very high doses have never had any organ toxicity.

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NEURO-INFLAMMATION AND GLIA – brain on fire.

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I mention Olympic athlete because so many people I see with Complex Regional Pain Syndrome – the pain that so often leads to suicide, seems to occur more often in top level athletes, either state or national level, professional or sponsored in their teens. Yes, they occur in others, but there is a striking predominance in athletes for unknown reasons.

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Glia are triggered by trauma, then they become activated and produce pro-inflammatory cytokines. Inflammation is out of balance. Ketamine profoundly reduces the pro-inflammatory cytokines, and so does low dose naltrexone. I write about these mechanisms with more frequency that anything else. This is what we must address – the brain is essentially “on fire.” And this inflammation, these pro-inflammatory cytokines, are involved in almost every known disease: Alzheimer’s disease, Parkinson’s disease, ALS, chronic pain, major depressive disorder, cancer, autoimmune disease, and atheroscloerosis.

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Inflammation kills. Unfortunately this new research on glia and inflammatory diseases, these diseases could be called gliopathies, all based on new research since the turn of the century. We now know glia are your innate immune system in brain and spinal cord. They need a balance the anti-inflammatory cytokines with the pro-inflammatory cytokines. Inflammation may be lifesaving when you have caught a virus, but not as a steady diet. Give the brain a break or it leads to hyperexcitable glutamate that triggers calcium flooding into the neuron, cell death, brain atrophy and memory loss. Seen in people with Major Depression and those with chronic low back pain.

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Do doctors know about the innate immune system? or the receptor that won the Nobel Prize 2 and 1/2 years ago? or glia?

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Answer: no.

..

Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

..

Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

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Dr. Papolos’ video on treatment points out, ketamine nasal spray is off-label

for Bipolar Disorder. And I add, ketamine is off-label for pain and for major depression.

He posts this:

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PUBLIC WARNING

.

Public Warning: 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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“Off label” means it is FDA approved for another purpose, but he prescribes it for Juvenile Bipolar Disorder. I would add that in qualified hands, ketamine is one of the safest medications we have in our formulary.

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More later, as time permits.

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PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
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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.

 

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~~~~~

The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

.

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

.

.

.

.

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Do You Have Depression? Are you the one who runs into snow wearing shorts?


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.Th

Since you were a baby, thermoregulation may be the source of the problem

that triggers your depression or the depression of someone you know.

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You may be a candidate for a research study if you have other key characteristics.

Treatment may help.

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Contact the Juvenile Bipolar Research Foundation.

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OR

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Demitri Papolos, MD, is the psychiatrist who, in collaboration with many others, has discovered that body temperature appears to be at the origin of this condition:

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Juvenile Bipolar Disorder, Fear of Harm phenotype.

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Dr. Papolos has written many publications and has published a book, with Janice Papolos, describing this serious disorder. “The Papoloses were the first to sound a national alarm about the dangers of using antidepressant and stimulant drugs with this population of children.”

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Either the link to Dr. Papolos or the Research Foundation, above, can give you further information on treatment.

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Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

..

Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

.

.

.

Dr. Papolos’ video on treatment points out ketamine nasal spray is off-label

for Bipolar Disorder and he posts this

.

PUBLIC WARNING

.

Public Warning: 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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“Off label” means it is FDA approved for another purpose, but he prescribes it for Juvenile Bipolar Disorder. I would add that in qualified hands, ketamine is one of the safest medications we have in our formulary.

..

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I am not affiliated with Dr. Papolos, but wish to call attention to the dedicated academic work they have been doing for this devastating mood disorder. .

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Of interest, thermoregulation appears to be modulated by low dose naltrexone (LDN).

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It has been anecdotally reported to relieve heat intolerance in persons with Multiple Sclerosis.

I have seen a response with Juvenile Bipolar Disorder/Fear of Harm, and

severe postmenopausal hot flashes were completely reversed by LDN.

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Naltrexone blocks the TLR4 receptor. There is a strong literature on TLR4 and temperature regulation. This raises the interesting question whether anyone has done objective studies to show that low dose naltrexone may be modulating temperature in patients. If you have experience with this, please add your comments below.

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~~~~~

The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

.

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

 

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Ketamine Inhaler – Bipolar Child NPR – Review of Ketamine for Depression


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NPR reported yesterday on the beneficial effects of ketamine for depression, this time reporting on a ketamine inhaler prescribed by Demitri Papolos, MD.

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Dr. Papolos is Associate Professor of Clinical Psychiatry at the Albert Einstein College of Medicine and Director of Research of the Juvenile Bipolar Research Foundation.

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He “is one of a handful of psychiatrists in the world who began to see and to speak out about the possible deleterious effects of antidepressants and stimulants in the population of children within the bipolar spectrum.”

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This NPR report described a syndrome Dr. Papolos has identified of Bipolar children & adolescents consumed by fear. They described a boy who had extreme attacks of rage for decades, and horrific violent nightmares.

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The boy had attempted suicide at age 5. He was hospitalized in a psychiatric unit at age 12 and strapped down in a padded room, terrified. He failed many medications for years, some made him worse, and he was literally never able to complete a meal at table with the family without flying off in a rage or someone leaving.

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in 2010, the boy tried Dr. “Papolos’ ketamine treatment. He says he’ll remember the day for the rest of his life. ‘I think we did two puffs, and I remember I sat up and I just started laughing,’ he says. Then his mother picks up the story: ‘You said you had an internal feeling of calm that you had never had before in your life. And when we came home that night, that was the first night that we ever all had dinner at the table without somebody leaving.'”

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This boy, George McCann, now at age 22 is finally able to begin a more normal life. He needs the medication only every third day. “Papolos has treated about 60 young people with ketamine so far and says all but two have had dramatic responses.”

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“The number of patients treated so far is small, and the approach is so new it hasn’t been tested by other researchers yet. Papolos says he’s hoping a study he published late last year will help persuade other researchers to try the drug on other children.”

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“In the meantime, George McCann continues to inhale a prescribed dose of ketamine every third day. The fear and anger that once dominated his life are gone, he says, adding that his mind is free now to work….”

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The relief with ketamine from the prison of mood disorders is deeply important. Severe mood disorders such as Major Depression and Bipolar Disorder can destroy the lives of patients and their loved ones. At worst, they can be lethal.

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A review of published cases of intravenous ketamine for depression asks : “Ketamine for depression: where do we go from here?

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I think the answer is we need to simplify the method of treatment using inhaled ketamine and begin to give their lives back to the patients we see. It is one of the safest medications I have ever prescribed. It does not cause weight gain or loss. It does not cause sexual dysfunction. And although it may increase sedation when used in combination with other sedating medications, at the low doses needed to treat mood disorders, I do not see ketamine interfere with other medication.

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Ketamine can relieve depression from one second to the next. And this young man needs the medication every third day. Is that too much to ask to gain a life?

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The material on this site is for informational purposes only, and is not a substitute for

medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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

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