Tegretol carbamazepine a safe option

One of the older but still more frequently prescribed drugs that is still used to treat peripheral neuropathy, is Carbamazepine (Tegretol). It's a well-known anti-seizure drug but has recently come under scrutiny regarding its interaction with certain HIV anti-retrovirals, especially Prezista (see here). Now, while I accept that reading every leaflet accompanying drugs can scare the life out of you and even if the side effects below are a worst case scenario, this drug information from drugs.com (see link below) shows that there are quite a few other considerations to bear in mind before taking Tegretol. I'm not an expert so concede that there may be very good reasons but question as to why it is still being promoted by the manufacturer and widely prescribed by doctors, when the potential side effects are so patently unpleasant and for certain HIV-patients, so dangerous?

Tegretol
Generic Name: carbamazepine (oral) (kar ba MAZ e peen) Brand Names: Carbatrol, Epitol, Equetro, TEGretol, TEGretol XR

What is Tegretol?

Tegretol (carbamazepine) is an anticonvulsant. It works by decreasing nerve impulses that cause seizures and pain.
Tegretol is used to treat seizures and nerve pain such as trigeminal neuralgia and diabetic neuropathy. Carbamazepine is also used to treat bipolar disorder.
Tegretol may also be used for purposes not listed in this medication guide.

Important information about Tegretol

Tegretol may cause severe or life-threatening skin rash, especially in people of Asian ancestry. Your doctor may recommend a blood test before you start the medication to determine your risk of this skin reaction. Seek emergency medical attention if you have a fever, sore throat, headache and skin pain, followed by a red or purple skin rash that spreads and causes blistering and peeling.

You should not take Tegretol if you have a history of bone marrow suppression, if you are also taking nefazodone, or if you are allergic to an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), desipramine (Norpramin), imipramine (Tofranil), or nortriptyline (Pamelor).

Tegretol may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking Tegretol for seizures. Do not start or stop taking Tegretol during pregnancy without your doctor's advice.

Do not use Tegretol if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days.

Before you take Tegretol, tell your doctor if you have heart disease, high blood pressure, high cholesterol, liver or kidney disease, glaucoma, a thyroid disorder, lupus, porphyria, or a history of mental illness or psychosis.

You may have thoughts about suicide while taking Tegretol. Your doctor will need to check you at regular visits. Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

There are many other drugs that can interact with Tegretol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Do not stop using Tegretol without first talking to your doctor, even if you feel fine. You may have increased seizures or unpleasant withdrawal symptoms if you stop using Tegretol suddenly.

Before taking Tegretol

Do not use Tegretol if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. You should not take Tegretol if you are allergic to carbamazepine, or if you have:
•a history of bone marrow suppression
•if you are also taking nefazodone; or
•if you are allergic to an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), desipramine (Norpramin), imipramine (Tofranil), or nortriptyline (Pamelor).

Tegretol may cause severe or life-threatening skin rash, especially in people of Asian ancestry. Your doctor may recommend a blood test before you start the medication to determine your risk of this skin reaction.

To make sure you can safely take Tegretol, tell your doctor if you have any of these other conditions:
•heart disease, high blood pressure, high cholesterol or triglycerides;
•liver or kidney disease;
•glaucoma;
•a thyroid disorder;
•lupus;
•porphyria; or
•a history of mental illness or psychosis.

Patients of Asian ancestry may have a higher risk of developing a rare but serious skin reaction to Tegretol. Your doctor may recommend a blood test before you start the medication to determine your risk of this skin reaction.

You may have thoughts about suicide while taking Tegretol. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

FDA pregnancy category D. Tegretol may cause harm to an unborn baby. Do not start taking Tegretol without telling your doctor if you are pregnant or planning to become pregnant. Use effective birth control while you are taking this medicine. Although Tegretol may harm an unborn baby, having a seizure during pregnancy could harm both mother and baby. If you become pregnant while taking Tegretol, do not stop taking the medicine without your doctor's advice. Seizure control is very important during pregnancy. The benefit of preventing seizures may outweigh any risks posed by taking Tegretol. Follow your doctor's instructions about taking this medicine while you are pregnant.

Carbamazepine can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using Tegretol. Carbamazepine can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking Tegretol.

How should I take Tegretol?

Take Tegretol exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.

Do not crush, chew, or break an extended-release Tegretol tablet. Swallow the pill whole. Breaking the pill would cause too much of the drug to be released at one time.

Shake the Tegretol oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

It may take up to 4 weeks before your symptoms improve. Keep using the medication as directed and call your doctor promptly if this medicine seems to stop working as well in preventing your seizures. Tegretol can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.

To be sure Tegretol is not causing harmful effects, your blood cells and kidney function may need to be tested often. Do not miss any follow up visits to your doctor for blood or urine tests. Your doctor may also recommend having your eyes checked regularly while you are taking this medicine.

Do not stop using Tegretol without first talking to your doctor, even if you feel fine. You may have increased seizures or unpleasant withdrawal symptoms if you stop using this medicine suddenly. Wear a medical alert tag or carry an ID card stating that you take Tegretol. Any medical care provider who treats you should know that you take seizure medication.

Store this medicine at room temperature away from moisture, heat, and light.

What should I avoid while taking Tegretol?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid drinking alcohol. It can increase some of the side effects of Tegretol, and can also increase your risk of seizures.

Avoid exposure to sunlight or tanning beds. Tegretol can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Grapefruit and grapefruit juice may interact with Tegretol and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Tegretol side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Tegretol: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have a serious side effect such as:
•pale skin, feeling light-headed, rapid heart rate, trouble concentrating;
•fever, chills, sore throat, mouth and throat ulcers;
•easy bruising or bleeding, severe tingling, numbness, pain, muscle weakness;
•confusion, agitation, vision problems, hallucinations;
•feeling short of breath, swelling of your ankles or feet;
•urinating less than usual;
•jaundice (yellowing of the skin or eyes); or
•severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious Tegretol side effects may include:
•feeling dizzy, drowsy, or unsteady;
•nausea, vomiting, diarrhea, constipation, stomach pain;
•headache, ringing in your ears;
•dry mouth, swollen tongue; or
•joint or muscle pain, leg cramps.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Tegretol?

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, other seizure medicines, and medicine for depression or anxiety can add to sleepiness caused by Tegretol. Tell your doctor if you regularly use any of these other medicines.

This list is not complete and there are many other drugs that can interact with Tegretol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

http://www.drugs.com/tegretol.html

Milnacipran Savella An Option For Neuropathic Pain

Today's post from prohealth.com (see link below) looks at the effectiveness of Milnacipran (brand names Savella, Ixel) in treating pain stemming from various neuropathic conditions; in this case concentrating on fibromyalgia but including peripheral neuropathy in most of its forms. You may not have heard of Savella because it's certainly not as widely prescribed as other serotonin–norepinephrine reuptake inhibitors (SNRI) like Duloxetine (Cymbalta) but from reading this article and appraisal, it certainly seems to be a viable alternative. This is especially true if you consider that they claim that there are far fewer mood disorders as side effects and as many patients on other anti-depressants will testify; that's a mighty big plus. This thorough article looks at the reasons why these medications are prescribed for nerve pain and the story of Savella itself. It's interesting to see how getting the process of approval from the American FDA works. As with any neuropathy treatment however; what works for some doesn't work for others, therefore these drugs should always be regarded as being alternatives for each other and if one group doesn't work for you, you move on to something else.

Fibromyalgia – The Savella Story
By Cort Johnson • www.ProHealth.com • September 7, 2015

Milnacipran (brand names: Savella, Ixel) is the third and last drug the FDA approved for the treatment of fibromyalgia in the United States. The fourth serotonin–norepinephrine reuptake inhibitor (SNRI), to be introduced in the U.S., Savella stops the reuptake of serotonin and norepinephrine in the nerves synapses – making more of those neurotransmitters available to the central nervous system. Savella is the most “balanced” SNRI in that it increases serotonin and norepinephrine equally. Unlike other SNRI’s it does not affect dopamine levels.

SNRI’s are usually considered antidepressants (although they are also often used to treat anxiety, obsessive compulsive disorder and ADHD) but two SNRI’s, Savella and Cymbalta (Duloexetine) have also been shown to be effective in treating chronic pain in some patients without mood disorders.

Several kinds of antidepressants (including TCA’s), in fact, are now commonly used to treat many kinds of pain including arthritis, central pain syndrome, fibromyalgia, low back pain, migraines, nerve damage from diabetes (diabetic neuropathy), and nerve damage from shingles (postherpetic neuralgia). Lower doses than used in depression are usually sufficient.

Pain Modulation

Different nerve pathways in the central nervous system can promote or inhibit pain. Reduced activity of the pain inhibition circuits appears to be the major problem in FM. The pain reducing circuits originating in the brainstem are loaded with neurons that respond to serotonin and norepinephrine. By increasing serotonin or norepinephrine levels, antidepressants may be reinvigorating the pain inhibiting circuits in the brainstem – thus lowering pain levels.

Antidepressants may also block receptors (histamine, NMDA, a-adrenergic) involved in pain processing, effect ion channel activity, (weakly) stimulate opioid receptors and may even affect immune regulation. Some recent animal model evidence suggests that Savella and similar drugs may enhance the effectiveness of microglial inhibitors such as minocycline.

It’s possible, even likely, that nerve pain and depression have an overlapping pathophysiology. Similar neurotransmitters, HPA axis, autonomic nervous system and immune alterations can be found in each.

The Savella Fibromyalgia Story

Savella has been the least of the big three drugs for FM. Cymbalta has been FDA approved for six conditions in the U.S., Lyrica for four and Savella for only one. Cymbalta is expected to challenge Lyrica for the top FM drug in sales, with Savella far, far behind.

Savella’s approval record is rather mixed, as well. Savella is FDA approved for treating fibromyalgia but not depression. Rather confusingly, it is not approved for fibromyalgia in Europe but is widely used for depression. It is approved for treating FM in Australia.

One of the advantages of getting FDA approval for a drug is that the drug tends to get more study. Since 2009, Savella has sparked numerous studies, with increasing studies in the last couple of years.

A 2010 review indicated that Savella can be effective in managing pain and improving fatigue and cognitive dysfunction as well as depression.

Side effects were limiting, however, with almost 25% of patients dropping out of clinical trials because of them. (Twelve percent of patients taking the placebo dropped out.)

One milnacipran review noted that most side effects vanish after a week or two and that slowly uptitrating the drug helps. The doctors recommended starting with 12.5 mg once daily in the morning for one week, then increasing to 25 mg once daily in the morning for 2 weeks, and then 50 mg once daily in the morning. In some patients they may add a evening dose.

Because milnacipran is the only FDA approved FM treatment shown to improve symptoms of fatigue and cognitive dysfunction in phase 3 clinical trials, they recommended using it in patients with brain-fog problems. They also noted that “many patients who have previously failed to respond to either of the other two indicated medications can have an excellent therapeutic response to milnacipran.”

A 2012 Cochrane Review, however, was not quite as enthusiastic. It stated that the drug does provide moderate pain relief (30% reduction) in about 40% of patients, but that placebo provided about a similar reduction to about 30% of patients. (The placebo response rate in chronic pain tends to be high. A later analysis found that almost 20% of FM patients on placebo in 18 studies experienced a 50% in reduction in pain.) In contrast to placebo, though, studies indicate that milnacipran (or Savella or Ibex) does appear to maintain its effectiveness long term.

A 2012 study found that the presence or absence of depression had little effect on milnacipran’s effectiveness in FM; i.e., the drug was effective or not independent of whether a patient was suffering from depression. Milnacipran was also associated with some weight loss (in a rather overweight FM population) over two years of treatment.

A long term analysis of 3,000 FM patients over 11 years, however, found that the FDA approved drugs for FM provided little extra benefit compared to past treatments (NSAID’s and opioids). Interestingly, as the FDA drugs came on line, opioid use in FM continued to increase; almost 50% of FM patients were using mild to strong opioids (mostly mild) by the end of the study. As the use of tricyclic antidepressants such as amitriptyline dropped (27-15%), the proportion of patients who were using Lyrica or the FDA approved antidepressants by the end of the study rose dramatically (about 40%). The new drugs increased costs for the patients, but study found that the clinical benefits of the new drugs were limited with 2-5% reductions in pain and no increases in functionality.

A large three-year study, however, found that 70% of FM patients on milnacipran reported themselves “much improved” or “very much improved.”

Meanwhile a quite small study found no significant differences in pain reduction or cognitive improvement between milnacipran and placebo. The home of the NIH institute for FM, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) got into the act by funding a CBT/milnacipran study that found “moderate benefits” to combining the two therapies.

Doctors had earlier reported that milnacipran was often effective in some FM patients who didn’t do well on other FM drugs. That report was largely borne out in a 2013 study that found that 33% of patients who did not respond to duloxetine (Cymbalta) were classified as responders to Savella.

By 2013 the drug industry was clearly tiring of meta-analyses finding rather low clinical benefits to their drugs. Researchers associated with major drug companies penned a review suggesting that these analyses “do not always tell the full story” and that some benefits had been missed.

A large 2013 study continued the push-back from the drug industry. A large study lead by an Eli Lily researcher found that patients using FDA approved drugs or tricyclic antidepressants reported “satisfaction with overall treatment and their fibromyalgia medication (46.0% and 42.8%, respectively)”. They also reported “modest improvements” and high rates of medication use.

Attempts to broaden the reach of milnacipran ensued. It proved to be helpful in reducing the frequency of migraine and headache, two common issues in FM, in a 2014 study. A 2014 analysis of three studies found that milnacipran did indeed improve fatigue significantly (30% reduction in fatigue) in about 15-20% of patients. A meta-analysis, however, suggested Savella was no better than placebo at reducing neuropathic pain.

Finally, the first pediatric study of milnacipran in FM had mixed results. The trial – co-authored by Lucinda Bateman – suggested the drug may improve symptoms of FM in kids at about the same rate as it does in adults, but the authors had so much difficulty enrolling pediatric patients that the trial was halted early.

Targeting Patients That Benefit – the Next Step

People with FM have had mixed results on Savella. That’s true for all FDA approved drugs for FM (and probably for all the recommended treatments for it). Lyrica, in particular, has a bad reputation for side effects – including the dreaded weight gain. (For Savella nausea seems to be the biggest problem.)

Realizing they have a PR problem, drug companies are trying to fine-tune who they are giving their drugs to. A recent study “Is the efficacy of Milnacipran predictable?” may be a harbinger of what’s to come. An analysis of three large trials revealed that one subset of FM patient benefited the most from Savella. It found that FM patients with high pain intensity, low anxiety or catastrophizing,
absence of major sleeping problems’ and significant physical limitations in the daily life did best. It suggested that if you have significant levels of anxiety (or catastrophizing), relatively low levels of pain and major sleeping issues you’re probably not going to benefit much from Savella. On the other hand, if you can get your anxiety and sleep under control – you might.

There are no magic bullets for FM but a 30-40% reduction in pain is nothing to sneeze at. People with fibromyalgia trying Savella might want to do two things

Consider whether you fit the above group

if you don’t, take steps to alleviate any of the above factors that might keep you from benefiting from Savella. 
Use the very slow ramp up period suggested by the doctors (see above) 

About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort's and other bloggers' work at Health Rising.

http://www.prohealth.com/library/showarticle.cfm?libid=21248

Is Virtual Reality Hypnotherapy A Treatment Option For Neuropathic Pain

Today's post from tandfonline.com (see link below) is a fascinating subject and of possible value for neuropathy patients looking for potential future options regarding their own treatment. It concerns a case study of a patient who has already undergone multiple standard neuropathy treatments without success and contacted one of the authors with a view to trying Virtual Reality Hypnotherapy. Her fascinating story and experiences are shown below and open up the possibility of sophisticated hypnosis being a very useful and possibly standard tool in the treatment of nerve pain in the future. As always, it's assumed cost will be a determining factor.

Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report 
Brent J. Oneal, David R. Patterson, Maryam Soltani, Aubriana Teeley, and Mark P. Jensen1,2 Volume 56, Issue 4, 2008

The publisher's final edited version of this article is available at Int J Clin Exp Hypn

See other articles in PMC that cite the published article.

Abstract

This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions.

Hypnotic analgesia has become an increasingly important aspect in the treatment of clinical and experimental pain (Lang et al., 2000; Montgomery, DuHamel; Redd, 2000) and has been used on virtually every type of pain (Patterson; Jensen, 2003). Patterson and Jensen reviewed 29 randomized, controlled studies of hypnotic analgesia and concluded that (a) the evidence supporting the efficacy of hypnotic analgesia is strong, and (b) hypnotizability is usually related to outcome in studies that measure this variable. With respect to the importance of hypnotizability, one potential strategy for increasing the impact of hypnosis is to make hypnotic induction less effortful. We hypothesized that by providing visual stimuli for a patient during hypnosis treatment and giving the patient an illusion of “sinking into a virtual world,” the induction would require less concentration and mental effort from the patient and therefore might be more effective than standard hypnosis. As Patterson, Tininenko, Schmidt, and Sharar (2004) posited, using computer-generated stimuli to capture and to guide the patient's attention may not only make the induction less effortful but also more widely available, given that such a treatment would not require the presence of a clinician trained in hypnosis.

Although there have been few attempts to apply computer-generated hypnosis to clinical situations, results from a recent study on procedural pain revealed that hypnosis delivered through immersive virtual reality (VR) was very effective in reducing patients' reported pain and anxiety and may have reduced the need for opioid analgesics (Patterson, Wiechman, Jensen, Sharar, 2006). Immersive VR hypnosis (VRH) isolates patients from the outside world. With VR, patients have the illusion of going inside the three-dimensional computer-generated environment. Because VR is designed to be a highly attention-grabbing experience, it reduces the amount of attention available to process pain and instead maximizes the person's ability to narrowly focus on a hypnotic induction thereby facilitating dissociation of pain. The goal of creating VRH was to develop a three-dimensional, immersive virtual reality technology that could guide the patient through the same steps that are used when hypnosis is induced through an interpersonal process.

While there is a recent interest in using VR as a medium for hypnosis, this application is relatively new and has primarily been applied to acute procedural pain. The purpose of this case study was to expand the use of VRH to the treatment of a patient with chronic neuropathic pain, and, to our knowledge, it is the first research of its kind. In addition, in the present study, we were able to compare the results of the current trial of VRH to the results of a previous trial of standard hypnosis (non-VR) treatment that was conducted with the patient a few years earlier by one of the investigators. We hypothesized that this patient would have a significant reduction in pain and achieve a greater and longer lasting reduction in pain with VRH than standard (non-VR) hypnosis.

Case History

The patient was a 36-year-old female with a 5-year history of C4 tetraplegia and upper extremity neuropathic pain. She had no psychiatric history and was otherwise healthy. Approximately 5 years prior to the initiation of VRH treatment, she was injured as the passenger in a motor vehicle crash and spent close to 4 months in a major regional trauma center. Since that time, she has participated in both inpatient and outpatient rehabilitation and has worked closely with medical staff through a major regional multidisciplinary pain clinic. She described her pain as a constant burning sensation along the lateral aspects of her shoulders, medial arms, and proximal/anterior forearms, which was worse in her left arm. She was unable to wear clothes with sleeves as those garments increased her pain. She was also unable to be outdoors when there was any wind or precipitation due to her pain. In addition, her pain was very sensitive to temperature, and if the temperature was more than a few degrees above or below 73° F, her pain intensified. Finally, she also reported significant sleep difficulties secondary to her pain.

She has tried many treatments for pain management over the years, including multiple medications, physical therapy, massage therapy, acupuncture, Tibetan sound therapy, meditation, and electrical stimulation. Also, as noted above, she participated in a clinical trial of standard (non-VR) self-hypnosis training (Jensen et al., 2005, 2008). She reported that all of those treatments had been relatively unhelpful in the reduction of her pain.

Regarding past medications, this patient has tried over 15 medications to help her with pain management, including oxycodone, methadone, oxcarbazepine (Trileptal), venlafaxine (Effexor), diazepam (Valium), lorazepam (Ativan), pregabalin, mexiletine, and triazolam. She used to meet with her physician through the multidisciplinary pain clinic once every 3 weeks for pain management. However, for the year prior to the time that this study began, she had been meeting with that professional about once every 2 months.

During this study, the patient was taking the following medications: Diazepam 5 mg SID for sleep and pain; oxcarbazepine 300 mg SID for pain; trazodone 100–150 mg SID for sleep; mexiletine 150 mg BID for pain; venlafaxine 150 mg in am/75 mg in pm for pain; and tolterodine (Detrol LA) 4 mg SID for treatment of an overactive bladder.

Procedure

The patient became known to us after she contacted one of the authors with an interest in virtual reality distraction after hearing about this in the media. She was told that virtual reality distraction is not well suited for chronic pain but also that we could provide virtual reality hypnosis to see if this might be of benefit for her. The first two authors met with the patient to explain the study and VRH treatment. She consented to participate. The measures and data collection procedures for this study were very similar to those used in a previous trial of standard hypnosis (Jensen et al., 2005). Baseline and follow-up data was obtained from the patient by telephone interview. In order to determine the longer-term effects of having participated in VRH, the patient was asked to take a hiatus from treatment for a 1-month period. During that time one of the authors contacted her on a weekly basis by telephone to assess her comfort with the treatment hiatus and she was told that at any time during the break, if her pain became too intense, she was welcome to return to VRH sooner than the 1-month timeframe. Session logs were completed with the patient before and after each VRH session. The treatment outcome measures analyzed for this case report included average pain intensity and pain unpleasantness, as well as amount of time (in hours) the patient experienced a reduction or absence of pain between treatment sessions. The patient was also administered the Stanford Hypnotic Clinical Scale (SHCS; Morgan; Hilgard, 1978–1979) in order to assess level of hypnotizability.

The patient participated in a total of 33 VRH treatment sessions over the course of 6-months. All sessions occurred in a private office at a regional trauma medical center in Seattle, Washington. All sessions involved the patient receiving an audio recording of a hypnotic induction, suggestions for pain relief, and then alerting while drifting through a three-dimensional computer-generated virtual world called SnowWorld (See Patterson, Tininenko, Schmidt, Sharar, 2004; Patterson et al., 2006 for details of SnowWorld). Between sessions, the patient was encouraged to practice self-hypnosis regularly by using the compact disc that was given to her with the audio of the VRH protocol. In other words, she could listen to the audio version of the hypnosis at home, but did not have the visual stimuli available during the at-home practice sessions. She was also asked to complete daily diaries of her pain, unpleasantness, and frequency of home practice throughout the 6-months of treatment. She e-mailed the diaries to the first author of this article.

The VRH program began by having the patient hovering at the top of the snow canyon while an audiotape of the hypnotist's voice prepared the patient for what she would experience during the virtual hypnosis. After approximately 6 minutes of instruction, she began a 6-minute descent in the “snowy” 3-D canyon and she experienced herself as floating by numbers (1 through 10, in order) and was instructed to deepen her relaxation as she passed by each number. At number 10, she was told that she was in her most relaxed state and had descended deep into the canyon. At that point, she experienced herself hovering above the lake and was given about 18 minutes of audio posthypnotic suggestions. That was followed by approximately 10 minutes of alerting as she ascended back up the “snowy” 3-D canyon and floated by numbers (10 through 1, in order).

The Nature of Hypnotic Suggestions

Although the exact transcript of the hypnotic suggestions is too long to report, we will provide examples of the content. First, there was an introduction to the lake. The lake was described to the patient, and she was encouraged to become increasingly absorbed in the scene and to let her body relax. Then the program addressed her mind and how it could be a tremendous resource to help her feel safe and comfortable. The next section discussed how pain affects her life. An example of this dialogue is, “Part of you knows what it takes to feel more comfortable, to allow you to heal faster. It is there, it's just that it only comes to you, to your awareness, during certain times of your life, and what you realize is that this part of your mind is going to become present in your life during this time of healing, or during the time when you are undergoing pain.” The following segment dealt with asking the patient to imagine a time before the trauma. She was then instructed to recall images from a time in the past when she had positive experiences and to remember how comfortable she felt then.

After she was asked to recall positive images and experiences from her past, she was directed to move forward in time and to continue to see positive images of herself functioning well. She was told that images from the past and from the future should start to have a strong connection. Then the patient was given suggestions for sleeping better through the night, and it was also suggested that any exercises she engages in would become easier. It was recommended that she change the experience of her pain to a sense of coolness or numbness, or even forget about it altogether. She was also guided that as her pain improved she would find the ability to continue doing things that make her feel better, such as increasing her movement and participating more in life. The lake segment concluded by giving the patient a chance to engage in any other experiences or images that she might like to have, or to give herself positive suggestions of her own. She was then provided a period of silence for her to do that. The final suggestion focused on the fact that her comfort would be far greater when she took off the VR helmet than it was before she started the session.

Outcome Measures

The outcome measures analyzed for this study included pre- to posttreatment through 1-month follow-up of average pain intensity and pain unpleasantness. These outcome measures were the two that demonstrated significant effects in the original hypnosis only (non-VR) study that this patient previously participated in (Jensen et al., 2005). Both outcome domains were assessed at each outcome assessment point by contacting the patient four times within a 7-day window, and asking her to rate her usual pain intensity and pain unpleasantness over the past 24 hours on 0 (no pain; not bad at all) to 10 (the most intense pain sensation imaginable; the most intense bad feeling possible for me) Numerical Rating Scales. The four ratings for each outcome domain were then combined into composite measures of average pain intensity and pain unpleasantness.

In addition, the patient rated pain intensity and unpleasantness before and after each VRH session, using the same 0 to 10 Numerical Rating Scales described. These ratings were averaged into separate composite scores. That is, the pre- and postsession pain intensity and pain unpleasantness ratings were averaged for both the first 10 sessions and also all 33 sessions of VRH. Developing the composite scores from the first 10 sessions of VRH allowed for a direct comparison between VRH and the standard (non-VR) hypnosis trial, which included 10 sessions of treatment. The final outcome measure was the amount of time (in hours) that the patient experienced a reduction or absence of pain between treatment sessions. In the same manner as described above, these ratings were averaged into separate composite scores (VRH-33 sessions, VRH-first 10 sessions, standard hypnosis-10 sessions).

Outcome Data

Relative to the pretreatment baseline, the patient's ratings of average pain intensity and pain unpleasantness were not significantly different from her posttreatment or 1-month follow-up ratings. This outcome was similar for both the current VRH study as well as the hypnosis (non-VR) study that was conducted in 2004–2005. See Table 1 for the patient's average pain intensity and pain unpleasantness ratings pre/posttreatment as well as at 1-month follow-up for both the VRH and hypnosis (non-VR) treatments. In other words, VRH did not create lasting changes in the patient's pain perception.



Table 1


Means and SDs of Average Intensity of Pain and Pain Unpleasantness at Pretreatment, Posttreatment, and 1-Month Fallow-Up for VRH and Hypnosis Treatments

However, when investigating pain levels immediately after treatment, the patient's average pain intensity levels and pain unpleasantness ratings from pre- to posttreatment session, there was a 36% reduction in her average pain intensity and a 33% reduction in her average pain unpleasantness from pre- to post-VRH (see Table 2). As explained above, in order to directly compare the VRH and hypnosis (non-VR) ratings, the first 10 sessions of the VRH treatment were compared to the 10 sessions of hypnosis (non-VR) treatment that this patient had previously completed. See Table 2 for a depiction of the VRH 10-session and the hypnosis (non-VR) 10-session ratings. This patient reported an average of 25% pain intensity reduction and 20% pain unpleasantness reduction over the course of the first 10 sessions of VRH, compared to an average of 7% pain intensity reduction and 15% pain unpleasantness reduction over the course of the 10-session hypnosis (non-VR) treatment.



Table 2

Means and SDs of Presession to Postsession Intensity of Pain and Unpleasantness of Pain for 33-Sessions of Virtual Reality Hypnosis (VRH33), 10-Sessions of Virtual Reality Hypnosis (VRH10), and 10-Sessions of Hypnosis (Hyp10)

With respect to the duration of pain decrease between treatment sessions, this patient reported an average of 12.21 hours of pain reduction and 3.86 hours of being pain free over the course of the 33 sessions of VRH treatment. For the first 10 sessions of the VRH treatment she reported an average of 8.5 hours of pain reduction and 4.3 hours of being pain free, compared to an average of 1 hour of pain reduction and 0 hours of being pain free over the course of the 10-session hypnosis (non-VR) treatment (See Table 3).




Table 3

Means and SDs of the Duration (in Hours) of No Pain and Reduced Pain Throughout the Course of 33-Sessions of Virtual Reality Hypnosis (VRH33), 10-Sessions of Virtual Reality Hypnosis (VRH10), and 10-Sessions of Hypnosis (Hyp10)

Finally, on the Stanford Hypnotic Clinical Scale (Morgan; Hilgard, 1978–1979), the patient received a score of 2, placing her in the low to low-moderate range of hypnotizability.

Discussion
 
This report represents our first attempt to apply immersive virtual reality hypnosis to treat chronic neuropathic pain in a woman with a spinal cord injury who had not responded to any form of prior treatment. The patient's subjective ratings of pain intensity and pain unpleasantness showed an immediate reduction that averaged 36% and 33%, respectively, from pre- to post-VRH treatment. In addition, the amount of time that this patient experienced no pain or a reduction of pain over the course of the 33 VRH-treatment sessions averaged 3.86 and 12.21 hours, respectively. Furthermore, when compared to hypnosis alone (non-VR), this patient experienced a greater reduction in pain intensity and pain unpleasantness as well as longer lasting freedom from pain throughout the course of treatment with VRH.

The fact that this patient's pretreatment ratings of pain intensity and pain unpleasantness were not significantly different from her posttreatment and 1-month follow-up ratings of pain intensity and pain unpleasantness suggests that VRH treatment was helpful for her on a time-limited basis, that is, on average, 12.1 hours. The relatively short-lived effect of VRH in this patient's case is consistent with recent research suggesting that although hypnosis may not “cure” a person's chronic pain, it can be an important part of a person's plan to manage chronic pain on a daily basis (Jensen et al., 2008). In other words, hypnosis can provide many patients with a means of coping with pain, much like they might use medications (that also provide only short-term relief), but without the negative side-effects of those medications. In fact, research suggests that hypnosis can provide many beneficial “side effects” (e.g., improved well-being, improved sense of control over pain, improved sleep, etc.) that can contribute to a patient's quality of life over and above its effects on pain (Jensen et al., 2006).

Thus, even though some patients (about between 20%–30%, cf. Jensen et al., 2008) with chronic pain can experience substantial and long-term reductions in average daily pain following hypnosis treatment, many more patients than this report some relief of pain via hypnosis, view it as helpful and continue to use it up to 12 months following treatment. Therefore, although the patient in this case report was not “cured” of her pain, which would have been surprising given the refractory nature of it, she did achieve meaningful benefits through the use of VRH that lasted for many hours. Furthermore, while overall pain measurements did not change substantially, observation of means suggests that the directions of changes were in the direction anticipated. Specifically, overall ratings went down during the treatment period rather than baseline and then increased again during the month with no treatment.

The findings that this patient, who has suffered from severe and chronic neuropathic pain for over 5 years and has tried a myriad of other interventions, including over 15 medication trials, achieved a significant and lasting reduction in her pain throughout the course of VRH treatment is extremely promising. It was interesting that the patient went through the efforts to come to the hospital for months; given her spinal cord injury this was logistically difficult for her. It was also noteworthy that she reported that she benefited more from the induction when it was paired to the visual stimuli, rather than presented simply through audiotape. She also chose to resume treatment after a 1-month no-treatment period requested by the investigators. During one of the final VRH sessions before the treatment hiatus, this patient indicated that over time she was learning how to control her pain better, largely due to the experience that she has received through virtual reality hypnosis.

It was also noteworthy that the patient scored low on a scale measuring hypnotizability. Although the Stanford Hypnotic Clinical Scale is a screening measure, it has been reported to have good correlations with the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C; Bryant, Guthrie, Moulds, Nixon, and; Felmingham, 2003). The fact that the patient had a good response to the virtual reality hypnosis with a relatively low hypnotizability score is encouraging to us. Our hope is that this technology will be most useful to patients that do not have a high level of hypnotizability. Specifically, it may be that providing attention-grabbing stimuli that matches the suggestions may help patients become more absorbed in the process when this does not come naturally.

We maintain that this patient's chronic neuropathic pain is a challenging clinical problem with no easy solution. This report is provided after 6-months of treatment, with an empirical hiatus of no treatment. Our hope is that with repeated treatment, the pain relief experienced by the patient will last for greater, and hopefully more extensive, periods of time.

There are several limitations to this case report. As with a study of this design, we are not controlling for historical factors that might have influenced the patient's pain perception; randomized controlled studies are necessary to control such extraneous variables. One of the biggest threats to validity is not knowing if the patient reported pain reductions simply to please the investigators. However, we should note that she was willing to report no reductions in pain over several periods during the study. Further, although historical confounds are always a consideration, it is difficult to argue that the drops in pain that occurred over almost all of the 33 treatments were attributable to anything other than the intervention. The activity required to travel to the hospital was more likely to exacerbate than to reduce pain in itself. Finally, this technology used in the intervention was novel and has not yet been refined for use. In spite of these drawbacks, however, we view the pain reductions that occurred with VRH, especially in light of previous poor response to other treatments, as promising and indicate that additional investigation of virtual reality hypnosis for chronic pain is warranted.

Footnotes

1This article was supported by grants from the National Institutes of Health (R01 GM42725-09A1 and R01AR054115-01A1) as well as with gifts or grants from the Paul Allen Foundation, Scan Design by Inger and Jens Bruun Foundation, Gustavus and Louise Pffiefer Research Foundation, and other private donors. The software expertise necessary to design the immersive virtual reality delivery system was provided by Hunter Hoffman, Ph.D., at the University of Washington Human Interface Technology Lab as well as Ari Hollander at Imprintit.com.

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References

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http://www.tandfonline.com/doi/abs/10.1080/00207140802255534?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U5_rnbFqQUM

Transdermal Buprenorphine A Safe Option For Nerve Pain

Today's post from diabetes.co.uk (see link below) is once again aimed at diabetics with neuropathy but applies to all those suffering from neuropathic pain. At first it seems promising, in these days of opioid hysteria. It suggests that a new opiate medication called transdermal buprenorphine, (a patch for the skin) can reduce neuropathic pain. However, if you look carefully at the study results, the numbers are so small as to hardly prove anything. It's good to see someone sensibly promoting the benefits of opioids to those living with chronic pain, especially when the rest of the media seems set on dismissing them as threats to the moral fibre of all nations but in this case, it may be advisable to wait until many more study results are released, over much wider and larger study groups, before getting too excited. Certainly worth remembering for the future and maybe later discussing with your neurologist.

Opioid medication shown to be effective on painful diabetic neuropathy
 Benedict Jephcote Fri, 22 Jul 2016

A type of opioid medication can ease the effects of pain as a result of diabetic neuropathy (nerve damage), a study has found.

A research team in Australia say the opioid pain medication, can help people who have moderate to severe diabetic peripheral neuropathic pain (DPNP).

DPNP is the name given to nerve damage which is caused by high blood sugar over a number of years and is one of the most common complications associated with diabetes. If left untreated it can lead to numbness, loss of sensation, and sometimes pain in feet, legs, or hands.

The study involved 186 people with type 1 or type 2 diabetes and stable glycemic control, who had been experiencing DPNP for at least six months.

They were split into two groups and were randomly given buprenorphine or placebo patches. Their pain levels and other symptoms of DPNP were logged in a daily patient diary and during clinic visits.

A high number of participants did not complete the trial, with 56 in the buprenorphine group dropping out and 69 people who were using the placebos.

Researchers said nausea and vomiting were the main reasons for early withdrawal in those who were testing the medication.

For those who remained, 86.3 per cent of the buprenorphine group experienced a 30 per cent reduction in pain after 12 weeks. By comparison, 56.6 per cent of the placebo group experienced this level of pain reduction.

The researchers wrote: "Transdermal buprenorphine, when tolerated, is an effective therapy for DPNP and provides another option to manage this challenging painful condition.

"Nausea and constipation need to be managed proactively to optimise treatment outcomes."

The study was led by Dr Richard W Simpson from Box Hill Hospital and Dr John H Wlodarczyk from Consulting Services in New Lambton, New South Wales, Australia. The study was published in the Diabetes Care journal and was supported by the manufacturers of the buprenorphine patch, Mundipharma.

http://www.diabetes.co.uk/News/2016/Jul/Opioid-medication-shown-to-be-effective-on-painful-diabetic-neuropathy-94646857.html

Marijuana Chewing Gum May Be An Option For Neuropathic Pain

Today's short post from news.morningstar.com (see link below) announces the arrival of cannabis chewing gum as an alternative to smoked or vaporised cannabis for pain relief. if and when it is apporved and developed to the right strengths for slow release cannabis, it could prove to be a very valuable option for people who can't smoke cannabis, or inhale it via various mechanisms. Chewing gum may be an acceptable means of delivering cannabinoids without the unpleasantness normally associated with smoking. Ironically, it can be equated to nicotine chewing gum which is used to help people stop smoking. This short article is aimed at MS sufferers but it applies to all people who suffer chronic nerve pain and other symptoms and could be an important development in the field of pain control.

MS patients may someday find relief in marijuana chewing gum
By Kathleen Burke, MarketWatch 8-17-15 11:06

Marijuana-infused gum enters clinical trials

Patients can smoke it, eat it and soon, they may be able to chew it.

Cannabis-focused biotech company AXIM Biotechnologies (AXIM) last week said it launched clinical trials on humans for medical cannabis chewing gum as a treatment for multiple sclerosis. The gum, MedChew RX, contains 5 milligrams of cannabidiol -- a non-psychoactive component of cannabis -- and 5 milligrams of THC -- a psychoactive cannabinoid.

Medical marijuana chewing gum "should allow for predictable and controlled release of the active ingredients," George Anastassov, chief executive of AXIM, said in a statement. It should not be socially stigmatizing, should have a pleasant taste and consistency and no undesirable side effects, he added. "Chewing gum meets all these criteria."

AXIM already has a cannabinoid chewing gum product, known as CanChew, on the market, however it does not contain THC and does not offer any medical claims.

The psychoactive component of THC is an effective way to treat patients with degenerative diseases, in addition to the medicinal properties of cannabidiol, which can be used to treat neurological conditions such as epilepsy. Additionally, the act of chewing helps preserve cognition and memory, as well as promotes overall oral health, Anastassov told MarketWatch.

While the current trials of the gum are only for MS patients, Anastassov says Axim hopes to expand the range of conditions it can be prescribed for.

"For multiple sclerosis, the market for treatment is quite large," Anastassov says. "Eventually, we will try to enlarge the conditions for this medication, such as pain." (More than 2.3 million people are affected by MS globally, according to the National Multiple Sclerosis Society.)

He says pain is one of the most predominant symptoms patients of a wide variety of diseases including MS suffer from globally, and there have been few game-changing drugs in the pharmaceutical market to help treat it.

There is no cure for MS, but current treatments work to speed recovery from attacks, slow the disease's progression and manage symptoms, according to the Mayo Clinic. The most common treatments used to manage symptoms are physical therapy, muscle relaxants and medications to reduce fatigue, depression and pain.

The Phase 1 trial of the gum is slated to begin in the second quarter of 2016. Though medical marijuana is legal in 23 states and the District of Columbia, it is classified on the federal level as a schedule I drug, which gives it the same illegal status as heroin and LSD and is considered to have no accepted medical use.

While the FDA has yet to approve any product containing cannabis, it has approved Marinol -- which contains dronabinol, a synthesized form of THC -- for anorexia, chemotherapy and AIDS patients. The FDA's website says it will continue to assess the effectiveness of marijuana for medical use, and will work with companies on medical cannabis research.

If the gum is approved by the FDA, it could be available in all 50 states, even if they have not legalized medical marijuana. "That's why we're going through the FDA," Anastassov says. "There's no ambiguity as to where it's legal."

-Kathleen Burke; 415-439-6400; AskNewswires@dowjones.com

http://news.morningstar.com/all/market-watch/TDJNMW20150817248/ms-patients-may-someday-find-relief-in-marijuana
-chewing-gum.aspx#.VdL9RQJMOlA.twitter