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Ketamine 0.5% and Amitriptyline 1% for Rosacea?

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Please note: There are no confirmed reports that this treatment for Etythmelalgia works for rosacea. There are a scant few anecdotal reports of using this treatment for rosacea which are collected in this topic (thread). You should find a doctor who is willing to write you a prescription for this and find a compounding pharmacist. You have been forewarned. 

An ointment made by Compounding Pharmacists of Ketamine 0.5% and Amitriptyline 1% in a Lipoderm cream used for Erythomelalgia has been reported by Deansm (scroll below) to improve rosacea.  

"Erythromelalgia is a clinical syndrome characterized by attacks in which the affected limbs become bright red, hot, and excruciatingly painful. The common trigger is heat exposure induced by exercise or increased ambient temperature. As the condition progresses, the limbs become permanently red, hot, and painful....According to various theories, erythromelalgia is a vascular disorder or neuropathic condition. In previous studies, we have shown that both systems are involved, but we do not know which one is affected first. It is plausible that the vascular and neuropathic components differ in each subject depending on the underlying cause....Nonetheless, this strategy offers the flexibility of easy application, no systemic adverse effects, and the possibility of combining it with other treatment options without concern of drug interactions. The combination gel has to be compounded by a pharmacist, which may be a problem for some patients, but it seems to be fairly easy to do and at a much lower cost than for most treatments commonly used."

Erythromelalgia is difficult to diagnose and to treat. For more information

The Cutting Edge
March 2006
Arch Dermatol. 2006;142(3):283-286. doi:10.1001/archderm.142.3.283
Combination Gel of 1% Amitriptyline and 0.5% Ketamine to Treat Refractory Erythromelalgia Pain
A New Treatment Option?
Paola Sandroni, MD, PhD; Mark D. P. Davis, MD

"Ketamine, sold under the brand name Ketalar among others, is a medication mainly used for starting and maintaining anesthesia. It induces a trance-like state while providing pain relief, sedation, and memory loss. Other uses include for chronic pain and for sedation in intensive care." Wikipedia

"Amitriptyline, sold under the brand name Elavil among others, is a medicine used to treat a number of mental illnesses. These include major depressive disorder and anxiety disorder, and less commonly attention deficit hyperactivity disorder and bipolar disorder. Other uses include prevention of migraines, treatment of neuropathic pain such as fibromyalgia and postherpetic neuralgia, and less commonly insomnia. It is in the tricyclic antidepressant (TCA) class and its exact mechanism of action is unclear." Wikipedia

"Pharmaceutical compounding (done in compounding pharmacies) is the creation of a particular pharmaceutical product to fit the unique need of a patient. To do this, compounding pharmacists combine or process appropriate ingredients using various tools. This may be done for medically necessary reasons, such as to change the form of the medication from a solid pill to a liquid, to avoid a non-essential ingredient that the patient is allergic to, or to obtain the exact dose(s) needed or deemed best of particular active pharmaceutical ingredient(s). It may also be done for more optional reasons, such as adding flavors to a medication or otherwise altering taste or texture. Compounding is most routine in the case of intravenous/parenteral medication, typically by hospital pharmacists, but is also offered by privately owned compounding pharmacies and certain retail pharmacies for various forms of medication. Whether routine or rare, intravenous or oral, etc., when a given drug product is made or modified to have characteristics that are specifically prescribed for an individual patient, it is known as "traditional" compounding." Wikipedia

There is a difference between a pharmacist and a compounding pharmacist. Whether your insurance covers a compounding pharmacist is another matter you will need to investigate. A prescription from a medical doctor is required for the compounding pharmacy to make the prescription. The ointment can be any type the pharmacist has available. This is like the old fashioned pharmacist who has a motar and pestal

Motar and Pestal


Wikipedia Commons

Deansm Report Using Ketamine 0.5% and Amitriptyline 1% for Rosacea

"Two months ago the GP I am seeing prescribed me an ointment containing Ketamine 0.5% and Amitriptyline 1%. Withing 3 days of using it twice a day the flushing disappered and my skin is white, the same as it was before Rosacea. It has been the same ever since for the last two months. I can eat, excersie, go out in the sun and nothing will bring on a flush. 
If anyone has this subtye and nothing has worked have a look into this, I have no side affects (the GP said it is very safe as the amount of active ingredients is too low and it's not absored systemically).......The packaging has no branding, it was made in a compounding pharmacy. He said he has found it helpful going back years for patients with Erythromelalgia and it was worth trying for my Rosacea as nothing else worked." Deansm

There are other anecdotal reports using this treatment which are shown in this thread by scrolling down to the December 5 and also the December 28 post listing them. 

 

 

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Sent the following question to the RRDi MAC Members (responses will be in this post): 

RRDi MAC Members, 

What are your thoughts on this treatment for rosacea: 

http://irosacea.org/members/forums/topic/3074-ketamine-05-and-amitriptyline-1-for-rosacea/

Responses

Amitriptyline is sometime used for treatment of migraine. There is an obvious link between certain rosacea features and migraine. 
We have in clinic seen some patients with good efficacy of anti-migraine agents (e.g. triptans) for rosacea. We are just now starting trials on this.

There may be a similar mode of action, at least for the amitriptyline.

Best

Alexander Egeberg, MD PhD

Gentofte Hospital
Department of Dermatology and Allergy
Kildegårdsvej 28
2900 Hellerup
Denmark 

--------------------------------------------

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Found one other anecdotal report, Despotic_Monarch, who reports, "The only thing out of 25 or so drugs/medications that worked is a cream base that contains... Ampitriptyline 1.0%/ Ketamine 0.5% cream in a 1 to 1 ratio. In just one week I went from being a tomato to a piece of paper and finally my skin can heal. If you are suffering from Rosacea this might be an amazing/safe treatment for you! Please see your derm."

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"Conclusions: A majority of patients with erythromelalgia (75%) reported improvement in pain with topical application of a compounded amitriptyline-ketamine formulation. The medication was well tolerated."

Neurology, Mayo Clinic
Topical amitriptyline combined with ketamine for the treatment of erythromelalgia: A retrospective study of 36 patients at mayo clinic
Timothy J. Poterucha, Sinead L. Murphy, Mark D P Davis, Paola Sandroni, Richard H. Rho, Roger A. Warndahl, William T. Weiss

JDD, March 2013 | Volume 12 | Issue 3 | Original Article | 308 | Copyright © 2013

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A similar compounding numbing cream that contains ketamine 5%, amitriptyline 2%, clonidine 0.2%, gabapentin 5% in a base of lipoderm has been reported by Elanor Linsel for dysautonomia. 

"The dysasthesia can be very disturbing for many patients and improved with amytriptyline or gabapentin." 

Rosacea: Choosing Among the Topical and Systemic Therapeutic Options
As the field of therapies available for rosacea has expanded, clinicians must weigh the topical and oral treatment options on a case-by-case basis
By Mark Bechtel, MD and Ann Bechtel, BSN, Practical Dermatology

 

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"Pharmaceutical companies are working to bring the combination to market, but it’s not yet available commercially, so Mayo Clinic dermatologists have their pharmacists compound it in two strengths – 2% amitriptyline and either 0.5% or 5% ketamine – using Lipoderm cream as the base, according to Dr. Davis. Patients apply the mixture three times daily. Why it works isn’t clear; the drugs have different and perhaps synergistic effects on skin pain.....Of more than 1,000 Mayo Clinic patients who have tried the combination, "I’d say less than 1% has told me that they’ve ever had a side effect," he said. "I’ve had just two or three patients tell me they’ve gotten nightmares," a known effect of ketamine. "This is a product that has great promise," he noted."

Dermatology News
Creams and patches can replace narcotics for skin pain
Publish date: December 4, 2013
M. Alexander Otto  Frontline Medical News

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"At this point, twice daily applications of topical 2% amitriptyline compounded with 0.5% ketamine in an organogel were added to the patient’s treatment regimen. The gel was initially applied only to the skin surrounding the affected area, but as the erosions healed the gel was applied to the area of herpetic infection."

Amitriptyline/Ketamine as Therapy for Neuropathic Pruritus and Pain Secondary to Herpes Zoster
JDD, February 2015 | Volume 14 | Issue 2 | Original Article | 115 | Copyright © 2015
John R. Griffin MD and Mark D.P. Davis MD

Topical gel combo decreases severe pruritus, pain in shingles-related case
Dermatology Times, March 16, 2015 By Bill Gillette

"In conclusion, this randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination of both in the treatment of neuro- pathic pain revealed no differences between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia."

Anesthesiology 2005; 103:140 – 6 © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain SyndromesA Randomized, Double-blind, Placebo-controlled Trial
Mary E. Lynch, M.D., F.R.C.P.C., Alexander J. Clark, M.D., F.R.C.P.C., Jana Sawynok, Ph.D.,‡ Michael J. L. Sullivan, Ph.D.

"This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial."

Clin J Pain. 2003 Sep-Oct;19(5):323-8.
A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain.
Lynch ME, Clark AJ, Sawynok J.

"This study demonstrates that topical 2% amitriptyline/1% ketamine, given over 6-12 months, is associated with long-term perceived analgesic effectiveness in treatment of neuropathic pain. Antidepressants and ketamine both produce multiple pharmacologic effects that may contribute to peripheral analgesia; such actions include block of peripheral N-methyl-D-aspartate receptors, local anesthetic properties, and interactions with adenosine systems."

J Pain. 2005 Oct;6(10):644-9.
Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study.
Lynch ME1, Clark AJ, Sawynok J, Sullivan MJ.

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Neuropathy & Neuralgia Therapies
Local Anesthetics, Gabapentin, Ketamine, Amitiptyline
❧ Bind to Na+, K+ and Ca2+ channels in damaged nerves to suppress abnormal spontaneous activity
❧ Disrupt G protein coupling to produce anti- inflammatory effects
❧ Typical usage has been shown to be safe and without serious adverse effects
❧ Consider surface area
Flores et al Rev Bras Anestesiol 2012;62(2):244-52, Shipton Anesthesiol Res Pract 2012:546409, Drugdex Evaluations [Internet]. Cited April 2012

Compounded Specialty Prescriptions in Women’s Primary Care
Natalie Gustafson, PharmD
Director of Pharmacy at Lloyd Center Compounding Pharmacy & Pacific Compounds Pharmacy
July 20, 2014
 

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Amitriptyline

Ketamine

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PainFree-IBU Fast Gel
• Ketamine 10%.......NMDA Blocker, Analgesic
• Gabapentin 4%..............Nerve Blocker
• Ibuprofen 10%...............Anti inflammatory
• Diclofenac 4%................Anti inflammatory
• Amitriptyline 1%.............Nerve Blocker
• Cyclobenzaprine 2%..... Muscle Relaxant
• Apply 0.5-1.0ml 3-4 x daily
• Use 1-4 drops on the affected area either alone or after the PLO gels. Response is in 1-2 minutes.

The Lost Art of Compounding June 18, 2010, Tom Schnorr, RPh, CCN
Apothecary Shop Pharmacy

 

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"In conclusion, this randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination of both in the treatment of neuro- pathic pain revealed no differences between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia."

Anesthesiology 2005; 103:140 – 6 © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain SyndromesA Randomized, Double-blind, Placebo-controlled Trial
Mary E. Lynch, M.D., F.R.C.P.C., Alexander J. Clark, M.D., F.R.C.P.C., Jana Sawynok, Ph.D.,‡ Michael J. L. Sullivan, Ph.D.

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Under Pharmacology, the (.5%) ketamine (and 1% amitriptyline) (mixing in a 1 to 1 ratio) compounds with either a base gel such as Lipoderm or cream such as pluronic lecithin organogel. The article notes that the Lipoderm administers the ketamine quicker and with better absorption.

Is Topical Ketamine Ready For Prime Time?
A literature review reveals limited evidence of efficacy, but larger studies are needed.
By Joseph Rabi, MD

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Other anecdotal reports using this treatment for rosacea

"To give a quick update, I have been using the compound cream 2x daily so far (started last Thursday evening, only four applications thus far), and I have no doubt that it is already helping my skin." BVokey post #s 82, 85, 90 and more

"The only thing out of 25 or so drugs/medications that worked is a cream base that contains... Ampitriptyline 1.0%/ Ketamine 0.5% cream in a 1 to 1 ratio. In just one week I went from being a tomato to a piece of paper and finally my skin can heal. If you are suffering from Rosacea this might be an amazing/safe treatment for you! Please see your derm." charles delacruz

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