Ketamine’s antidepressive effects
tied to opioid system in brain
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click above name to go directly to the website for this dharma teaching – it will be easier to read.
.http://www.judithragir.org/2014/01/exhaling-and-dissolving/
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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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In a new analysis published Wednesday in the journal Scientific Reports, UC San Diego researchers said millions of FDA side effect records reveal that people who took ketamine for pain relief reported lower rates of depression.
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“The occurrence of complaints about depression dropped in half after ketamine administration,” said UC San Diego Skaggs School of Pharmacy professor Ruben Abagyan, who led the study.
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The researchers focussed on the FDA’s Adverse Effect Reporting System, a database that tracks negative side effects among people who take various drugs. But the researchers were not primarily interested in bad outcomes.
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Instead, they looked for a positive outcome: declining rates of depression among people taking drugs not typically thought of as antidepressants.
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They found signs that other common drugs — including Botox, a pain reliever called diclofenac and the antibiotic minocycline — also reduced depression among patients in the FDA database.
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[minocycline is a glial modulator and it can prevent CRPS from spreading.]
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University of Miami psychiatry professor Charles Nemeroff wrote that the study was, “very interesting.”
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“The findings are of considerable interest. However the interpretation of the findings are key,” he wrote, saying it will be important to understand whether ketamine is directly treating depression or simply relieving pain, which can indirectly help people experience less depression.
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The UC San Diego researchers said they controlled for this variable by comparing people who took ketamine with those who took other pain medications. They said they still found a larger drop in depression among those who took ketamine.
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HIGHER BLOOD LEVELS OF CAFFEINE CORRELATED WITH LESS INFLAMMATION
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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.
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.
CONCLUSIONS: This study suggests that ketamine is effective in treatment-resistant bipolar depression and may reduce suicidal ideation and anhedonia.
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snip
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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.
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!
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Quoting from the New York Times today, a subject often encountered daily, so rarely discussed in the media. My own colleagues cannot afford health insurance deductibles, let alone the average person who is not a medical professional. Five compounding pharmacies have closed in the last few months! Compounded medications are no longer covered! My patients cannot afford the insurance denials for medications, and how are we practicing medicine when each visit must be taken up with prior authorizations? No wonder the cost of medical care has gone up. What do we do for chronic pain or treatment resistant depression when our people have failed all drugs? Research funding never seems to go toward pain or depression.
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Re “Many Say High Deductibles Make Their Health Law Insurance All but Useless” (news article, Nov. 15):
My self-employed husband and I have found ourselves in this predicament: affordable health care premiums but a prohibitive $5,000 yearly deductible.
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Truly accessible health care cannot be achieved when insurance companies are the primary beneficiaries of policies and when those who are “insured” still cannot afford to see a doctor.
SUSAN A. McGREGOR
North Kingstown, R.I.
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To the Editor:
Your article does a good job of describing cost-shifting from insurance companies to medical consumers but doesn’t explore the issue of risk-shifting.
People pay insurance companies premiums to take on risk. Insurance companies try to avoid as much risk as they can. High deductibles and co-payments are just part of the risk-shifting.
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Other strategies being used include narrow networks of doctors and hospitals, denial of access to high-quality and often high-cost specialists, questioning and limitation of access to expensive drugs, questioning and limiting high-cost testing, and even offering free health club memberships to screen out those with high-cost disabilities.
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At a health insurance fair in San Francisco earlier this month, participants selected from various plans offered through the Affordable Care Act. Credit Jim Wilson/The New York Times
This process is about a lot more than high deductibles. But the end result is that good people are not getting the care they thought that they paid for. And the political leaders of both major parties approve these hassle factors — as our courts do — in the name of preserving America’s global competitiveness.
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BRANT S. MITTLER
San Antonio
The writer is a cardiologist and a lawyer.
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To the Editor:
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So at the end of the day, health care is no more affordable than it was before Obamacare was enacted! Why should we be surprised?
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Several decades ago, in an effort to promote “wellness,” we saw an increasing trend to encourage people to visit their doctor more regularly and more often, by offering plans that covered basic health maintenance costs. State regulations demanded coverage of some services, and the Affordable Care Act only added to the list that must now be provided without cost to the user.
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Insurance in the traditional sense provides coverage for the unforeseen event. In health care, that would be serious injury and catastrophic disease. What we have today is what the insurance industry refers to as “trading dollars.”
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Imagine if car insurance covered all basic services to reduce the risk of future damage, like oil changes, new brakes and even periodic visits to the car wash. We would see huge increases in the cost of car insurance, although we would also see policies that are offered at low premiums but with high deductibles and high co-payments.
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MICHAEL A. SMITH
Wells, Me.
The writer is a retired equity research analyst who covered the insurance industry.
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To the Editor:
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Your article about high deductibles in health insurance was accurate as far as it went, but a complete discussion of the benefits of health insurance coverage would have included the fact that insurers negotiate substantially reduced payments for in-network medical services for the insured.
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I have a high-deductible policy, but the payments I have to make to an in-network provider are usually only 40 to 50 percent of what I would have paid if I had been uninsured.
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An emergency room physicians’ bill here on my desk lists $632 as the charge, for which the insurer’s negotiated rate was $273.27, a 57 percent discount.
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My high-deductible health insurance policy is a membership in a huge discount medical services program. This is an important consideration that should be discussed more openly. The uninsured, by paying full freight, are subsidizing health care for those of us who are insured.
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DAVID MAIER
Richmond, Va.”
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FDA mandated that manufacturers of extended release opioids fund the conferences.
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Andrew Gelman, statistician at Columbia University and writer for the Washington Post, argues in his blog against the rate being higher at all. His conclusion: “…death rates among middle-aged non-Hispanic whites in the U.S. slightly increased, even while corresponding death rates in other countries declined by about 30%.”
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30 mg Oxymorphone (Opana) use not recommended
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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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Please ignore the ads below. They are not from me.
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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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Please ignore the ads below. They are not from me.
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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.
~~~~~
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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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.
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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Glia are key players in a number of nervous system disorders. Besides releasing glial and neuronal signaling molecules directed to cellular homeostasis, glia respond also to pro-inflammatory signals released from immune-related cells, with the mast cell being of particular interest. A proposed mast cell-glia communication may open new perspectives for designing therapies to target neuroinflammation by differentially modulating activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be upregulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N-acylethanolamines, whose principal family members are the endocannabinoid N-arachidonoylethanolamine (anandamide), and its congeners N-stearoylethanolamine, N-oleoylethanolamine, and N-palmitoylethanolamine (PEA). A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: PEA is produced and hydrolyzed by microglia, it downmodulates mast cell activation, it increases in glutamate-treated neocortical neurons ex vivo and in injured cortex, and PEA levels increase in the spinal cord of mice with chronic relapsing experimental allergic encephalomyelitis. Applied exogenously, PEA has proven efficacious in mast cell-mediated experimental models of acute and neurogenic inflammation. This fatty acid amide possesses also neuroprotective effects, for example, in a model of spinal cord trauma, in a delayed post-glutamate paradigm of excitotoxic death, and against amyloid β-peptide-induced learning and memory impairment in mice. These actions may be mediated by PEA acting through “receptor pleiotropism,” i.e., both direct and indirect interactions of PEA with different receptor targets, e.g., cannabinoid CB2 and peroxisome proliferator-activated receptor-alpha.
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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.
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For My Home Page, click here: Welcome to my Weblog on Pain Management!
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Psychiatrists from Mt. Sinai in New York this month have published the first randomized controlled trial of intranasal ketamine showing it is safe, well tolerated, and rapidly effective in treating symptoms of depression in persons with Major Depressive Disorder.
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This is a small study of 18 patients with treatment resistant depression showing a significant antidepressant effect occurred as early as 40 minutes in some. 44% responded after 24 hours compared to 6% placebo. Ketamine was significantly different from placebo at 40 minutes, 240 minutes, and 48 hours, but not separable from placebo at 72 hours or 7 days thought they were still better. And ketamine was significant at improving anxiety symptoms at 24 hours. There were no clinically significant changes in heart rate or blood pressure and all changes resolved in four hours. “No serious adverse events occurred.”
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“Intranasal ketamine was well tolerated with only very minimal increases in dissociation, psychosis-like symptoms or hemodynamic parameters.” They felt these very minimal behavioral side effects and insignificant changes in blood pressure and pulse were consistent with the lower blood levels of ketamine compared to the higher doses used in studies of IV ketamine. Bioavailability via intranasal route is reported to range from 25% to 50%.
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Their sample had an average of 4.1 ± 3.9 treatment failures, compared to 5.7 and 5.1 in previous studies – those required a minimum of 2 to 3 treatment failures to enroll. Other clinical characteristics did not differ including “duration of illness, length of current depressive episode, and history of ECT.” They allowed ongoing treatment of psychotropic medication.
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They chose a 50 mg dose based on a previous study and on the dose used in persons with a chronic pain disorder (Daniel Carr, et al 2004). It is a lower dose than the 0.5 mg/kg dosage commonly given intravenously. They point out one limitation of the study was the use of the single dose and a standardized protocol, which did not allow them to study optimal dosing. Future study is needed to address optimal dosing, relapse prevention and scheduling of treatment.
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The minimal side effects shown in their study correlates well with my experience. I find the effective dose of ketamine is idiosyncratic. That means it is unpredictable and specific only to that individual. Large males may need only the smallest dose, and tiny elderly females may require far higher doses. That may account for the higher response rate that I believe I am seeing, however, I have not tracked percentage of responders. I have not seen toxicity in years of prescribing either for intractable pain or treatment resistant depression. Importantly, in my opinion, relapse prevention must address not only different neurotransmitters but also neuroinflammation, pro-inflammatory cytokines.
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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.
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For My Home Page, click here: Welcome to my Weblog on Pain Management!
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Clin Rheumatol. 2014 Feb 15. [Epub ahead of print]
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.
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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.
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For My Home Page, click here: Welcome to my Weblog on Pain Management!
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