Older updates from June 2008 to the end of 2009
29th December 2009
A new study to be published in the journal Anaesthesia and Analgesia concluded that the synthetic cannabinoid nabilone (Cesamet p. 246) was superior to the more traditionally used amitriptyline (Elavil, pp. 113-114) in treating sleeping problems in fibromyalgia. Neither drug improved pain, mood or quality of life, however.
2nd December 2009
Unfortunately the FDA has sent a complete response letter to Hemispherx Biopharma's rintolimod (Ampligen, pp. 222-223) new drug application (NDA) rejecting to approve it. The FDA wants the company to conduct more studies to prove both the efficacy and safety of Ampligen. They're particularly concerned about the possibility that Ampligen could cause autoimmune diseases or heart problems. Now the company must conduct those studies and submit a new NDA, likely pushing the possible approval of Ampligen to 2011 at the soonest.
In other news on the approval front, the European equivalent of the FDA, EMEA, recently rejected milnacipran (Ixel/Savella pp. 124-125) as a treatment for fibromyalgia. This is not particularly problematic, as milnacipran is already widely available in Europe as the antidepressant Ixel and can still be prescribed for fibromyalgia, but it does pose an interesting question: why has the EMEA rejected extending the indication of all the three medications that the FDA has approved for treatment of fibromyalgia?
10th October 2009
The news has been buzzing about the study connecting the retrovirus XMRV to CFS/ME. But what does this finding really mean? Maija Haavisto wrote an article to answer the questions. She is not keen on the idea of antiretroviral drugs (unless someone shows them curative) with so many effective and safer treatments around.
Contrary to the results of the lidocaine study mentioned in the 10th March update, a study presented as a poster in EFIC's Pain in Europe VI conference did not find the combination of lidocaine and the tricyclic antidepressant amitriptyline (Elavil, pp. 113-114) more effective in the treatment of fibromyalgia than amitriptyline alone. The 240 mg dose of lidocaine appears to have been adequate, unless the patients were very heavy, but a possible reason for the failure of this normally very effective treatment is that lidocaine works by blocking sodium channels and this may also be the primary pain relieving effect of amitriptyline. Perhaps they should have used a different treatment (such as an SNRI) for the comparison). The short abstract-like poster did not include any comparison of side effects.
21st September 2009
A new study presented at the 22nd European College of Neuropsychopharmacology (ECNP) Congress found the drug ropinirole (Requip, p. 160) helpful in reducing the symptoms of fibromyalgia in patients already taking at least one medication. Ropinirole reduced scores on pain, sleep and anxiety/depression scales. However, the drug also caused side effects, especially nausea/vomiting. 10 of the 28 patients withdrew from the study prematurely, six of them citing the side effects. Previously one preliminary paper has been published on ropinirole in fibromyalgia, but it was back in 2003.
Two recent phase III studies found a 14-day course the nonsystemic antibiotic rifaximin (Xifaxan, pp. 93-94) helpful for non-constipation irritable bowel syndrome (IBS). Rifaximin has been used in the treatment of IBS when there is suspicion of small intestinal bacterial overgrowth of SIBO (also known as dysbiosis of the gut), because it can reduce the amount of harmful bacteria in the gastrointestinal tract without being absorbed into the body. Salix Pharmaceuticals, the company producing rifaximin, plans to submit a new drug application (NDA) of this use to the FDA in 2010.
6th July 2009
Some new CFS/ME research of value has been published. In February this page reported that a new U.S. clinical trial is trying rituximab (Rituxan) for CFS/ME. Now a new case series published in the journal BMC Neurology describes three patients who experienced improvement (from mild to major) in their CFS/ME symptoms from this immunosuppressant. Two of the three were also tried on methotrexate, an older chemotherapy drug used as a less selective immunosuppressant and one of the two benefited from this treatment. While these findings sound promising, immunostimulants are generally a much safer treatment for CFS/ME (as well as autoimmune diseases) without the need to worry about cancer, opportunistic infections or other serious complications.
Aa Belgian research group (including Kenny Meirleir) compared the intestinal flora of 108 CFS/ME patients to that of 155 healthy controls. A significant increase in the number of some lactic acid producing bacteria (Enterococci and Streptococci) was found in the patient group. The abstract from the journal In Vivo notes that "Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications." It might give more weight to the use of certain antibiotics like rifaximin (pp. 93-94) to treat dysbiosis of the gut in CFS/ME. The implications of this study on probiotic treatment are unknown. Previous studies on the gut flora of CFS/ME patients have found a deficiency of bifidobacteria.
Another study, from Neuropsychiatric Disease and Treatment, posits that the fatigue and other neuropsychiatric symptoms in CFS/ME and other neurological diseases may stem from autoimmunity affecting some important neuropeptides, causing "leakiness" of the blood-brain barrier. They suggest the PDE4 inhibitor drug rolipram as a potential treatment. It is not currently on the market anywhere, but other PDE4 inhibitors like pentoxifylline (pp. 181-182) and ibudilast (p. 277), could be used. PDE4 inhibitors have been studied in e.g. depression and multiple sclerosis, but they usually cause too many side effects and most have been discontinued before ever being marketed, ibudilast being a notable exception. The article also lists the antidepressant imipramine (p. 115) as a potential treatment for this autoimmune blood-brain barrier disturbance.
27th May 2009
Another intriguing new fibromyalgia study is to be published in Clinical Rheumatology. It is about tegaserod (Zelnorm), a drug used in the treatment of irritable bowel syndrome (IBS). The study found that patients with both fibromyalgia and IBS experienced a significant decrease in fibromyalgia symptoms, such as pain and tender point count, when taking tegaserod for their IBS. Tegaserod is a (partial) agonist of the 5-HT4 serotonin receptor. Previously many studies have found antagonists of the 5-HT3 serotonin receptor (granisetron, ondansetron and tropisetron, pp. 259-260) which are primarily used as antiemetics (for nausea caused by chemotherapy) to be helpful in both IBS and fibromyalgia, but this was the first study evaluating a drug acting on the 5-HT4 receptor.
Unfortunately the 5-HT3 antagonists are extremely expensive while tegaserod has been withdrawn from the market in the U.S. (and most other markets?) due to concerns over possibly increased cardiovascular risk. Several other 5-HT4 agonist drugs exist besides tegaserod, but most of them have either been withdrawn as well, are only in clinical trials or have many other pharmacological properties (like the antiemetic metoclopramide). Cisapride (Prepulsid) might be a viable option, but it too is only available in Australia and some European, Asian and South American countries.
7th May 2009
In a new study published in the journal In Vivo parvovirus B19 DNA was detected from the gastrointestinal mucosa of 40% of CFS/ME patients but only 15% of controls. This isn't the first study to implicate the role of parvovirus B19 in CFS/ME, but still the results are somewhat surprising. There are no specific antiviral treatments against parvovirus B19, but intravenous immunoglobulin (Reviving the Broken Marionette, pp. 207-208) has been reported to be curative in some cases of CFS/ME caused by parvovirus B19.
The results of the first study of low dose naltrexone (LDN, pp. 214-215) for fibromyalgia were finally released. Maija Haavisto considers LDN the best treatment for both fibromyalgia and CFS/ME. In the small placebo-controlled study, to be published in the journal Pain Medicine, LDN produced very significant improvement in pain and fatigue compared with placebo. The researchers at Stanford university are currently conducting a study of LDN for juvenile fibromyalgia - great news, as there very few studies of treating fibromyalgia in children have been done.
Another interesting new study published in the Journal of Pain has found that in low doses the beta blocker propranolol (Inderal, p. 176), commonly prescribed for palpitations, anxiety and migraine prevention, can significantly reduce pain from both fibromyalgia and temporomandibular joint disorder (TMJ/TMD). Because propranolol is a very common drug, fibro/TMD patients should not have much difficulty getting a prescription, if they want to try it out themselves (the research is preliminary, but low doses of propranolol are unlikely to cause major side effects).
10th March 2009
More new research about IV treatments. A study to be published in the journal Clinical Rheumatology found intravenous lidocaine (Reviving the Broken Marionette pp. 67-68) effective for fibromyalgia and the efficacy was maintained 30 days after the last infusion (most likely much longer, but they only tested at 30 days). This was, however, an open-label study (not placebo-controlled), but lidocaine is difficult to administer blindly anyway, even as an IV infusion. Hopefully this study will lead to bigger future studies and to increased use of IV lidocaine as a treatment for fibromyalgia.
4th March 2009
A new placebo-controlled study about the intravenous nutrient therapy Myers' cocktail (p. 249) in the treatment of fibromyalgia has been published. The treatment resulted in marked improvement in all parameters, but because the study was fairly small and the placebo group also improved, the treatment effect was not statistically significant. It should be noted that the "placebo" was an intravenous infusion of Ringer's lactate, which may not be a true placebo, as intravenous saline infusions (pp. 250-251) are helpful for many patients with CFS/ME. CFS/ME specialist David Bell has even voiced an opinion that blood volume expansion may explain the efficacy of many therapies given as IV infusions.
22nd February 2009
The pharmaceutical company UCB has announced the results of two studies relevant to people with CFS/ME and fibromyalgia. Unfortunately this time the results were disappointing. The results of neither the phase IIa study of lacosamide for migraine prophylaxis (prevention) nor phase IIa study of rotigotine for fibromyalgia reached statistical significance for their primary endpoints. This does not mean that these medications are now deemed completely ineffective for these purposes, but they were less effective than thought and there will probably be no phase III studies. Lacosamide (Vimpat) is an anticonvulsant recently approved in the U.S. which has been in successful clinical trials for fibromyalgia. Rotigotine (Neupro, p. 164) is a dopaminergic drug only available as a patch.
On the CFS/ME front, the final decision date for the FDA approval of Ampligen (pp. 222-223) was postponed by three months, from February 25th to May 25th. By this date we should find out whether the FDA will approve Ampligen as the first drug indicated for the treatment of CFS/ME.
An interesting U.S. clinical trial will be trying the monoclonal antibody rituximab (Rituxan) as a treatment of CFS/ME. It is used in illnesses characterized by excess of B cells, including some autoimmune diseases, lymphoma and leukemia. It is an immunosuppressant and patients with evidence of viral infection are not allowed in the study, which is rather peculiar when the illness studied is generally considered to be a chronic viral infection, as is the case of CFS/ME.
16th January 2009
Here's the news that have been expected: milnacipran (pp. 124-125) was approved by the FDA for the treatment of fibromyalgia, to be sold with the brand name Savella. This is now the third drug approved for the treatment of FM in the U.S., and the first one to be approved without a previous indication (milnacipran is an SNRI antidepressant like duloxetine (Cymbalta, p. 124) and has been used to treat depression in Europe, but has not been approved as an antidepressant in the U.S.) Milnacipran may be better tolerated than Cymbalta, and at least here in Europe it is also very inexpensive.
The next drug approved for fibromyalgia will probably be sodium oxybate (Xyrem, p. 32). Another new study recently vouched for its efficacy and tolerability in this use.
30th December 2008
A large new study about the SNRI antidepressant milnacipran in fibromyalgia (Ixel, pp. 124-125) involving over 1,000 patients has been published in Clinical Therapeutics. Milnacipran was found to reduce pain significantly already after one week. It also helped fatigue and functionality. About 20% of those taking milnacipran and 10% of the placebo group dropped out prematurely due to side effects. This study makes it likely that milnacipran will soon be approved by the FDA for fibromyalgia (it is not yet available in the U.S., but is used for depression in many European countries).
23rd November 2008
An interesting new analgesic tapentadol has been approved by the FDA. Tapentadol is an opioid painkiller somewhat similar to tramadol (Ultram, p. 58), but instead of increasing the reuptake of serotonin and norepinephrine (noradrenaline), it only increases the reuptake of norepinephrine. This may make it better tolerated than tramadol for some people. It should be a good painkiller for those with fibromyalgia, and probably for CFS/ME as well.
In other news levetiracetam (Keppra, p. 82) should now (or soon) be available as a generic drug. This is very good, as levetiracetam may be the best tolerated anticonvulsant, but in large doses it has tended to get quite expensive. Also granisetron (pp. 259-260) is now available as a transdermal patch with the brand name Sancuso.
30th October 2008
FDA has approved lacosamide (Vimpat) for the treatment of partial-onset seizures, a type of epilepsy. This is great news for patients with fibromyalgia, as well, as lacosamide has been found to be effective in fibromyalgia (see the entry for 25th June) and it could be prescribed for FM off-label. It could also be helpful for people with CFS/ME. Lacosamide was approved for the EU market a few weeks ago.
Lacosamide has a novel mode of action, meaning that no other drug works the same way. Thus it could help those who haven't benefited from other treatments - even though it is fairly unlikely that someone would not benefit from any other treatments but lacosamide, considering there are over 250 medications that can be used to treat fibromyalgia and CFS/ME. On the other hand, as many anticonvulsants are widely used in the treatment of chronic pain, doctors may be more likely to prescribe lacosamide for fibromyalgia patients, compared to more "experimental" treatments.
28th October 2008
It has been quiet on the research front, hence the lack of updates. There is one recent case report of interest, published in the Journal of Musculoskeletal Pain. A patient who had both fibromyalgia and ADHD and whose pain had not responded to several therapies responded "dramatically" to atomoxetine (Strattera, p. 126), with 60% reduction in fibromyalgia pain and marked improvement of her functional status.
Many important CFS/ME and fibromyalgia drugs are still waiting approval from FDA and/or EMEA, the European Medicines Agency. EMEA recently decided to recommend European approval of the sleep aid eszopiclone, which is to be sold as Lunivia in Europe (p. 26). However, EMEA also rejected to extend the indication of duloxetine (Cymbalta, p. 124) for the treatment of fibromyalgia, even though the FDA has already approved duloxetine for this indication. Obviously duloxetine can still be prescribed for fibromyalgia (and CFS/ME) off-label in Europe.
19th August 2008
A new paper published in the journal Medical Hypotheses suggests iodine deficiency as a possible cause of subclinical hypothyroidism which may underlie fibromyalgia and other illnesses. There is already evidence that thyroid problems may be behind a subset of fibromyalgia cases (see pages 198-200 in Reviving the Broken Marionette) and iodine deficiency might be a causative factor. Please note that this is not a scientific study, only a paper describing the hypothesis. You should discuss any possible iodine supplementation with your doctor.
In other, slightly more worrisome news, a recent study suggests some sleeping pills, particularly the "Z drugs" and ramelteon (pp. 31-32), as possible carcinogens (the possible carcinogenicity of zopiclone is actually discussed in the book on page 26). It is peculiar if ramelteon turns out to be carcinogenic, as it binds to melatonin receptors and there is a wealth of evidence that melatonin has anticancer properties. There is no clear-cut evidence that these drugs cause cancer, but if you are worried you may want to bring it up with your physician. Melatonin remains a safe choice, but like all drugs it is not for everyone. Reviving the Broken Marionette also reviews dozens of other drugs than can help insomnia and other sleep disorders.
25th June 2008
There are good news for fibromites again (it looks like we are on a roll here!). A phase IIa trial found the novel anticonvulsant lacosamide effective for fibromyalgia. The drug was also found "very well tolerated." Lacosamide is not included in Reviving the Broken Marionette, because it has not yet been approved anywhere. FDA and the European Medicines Agency are currently reviewing the company's new drug application and the drug could be approved for use in partial-onset seizures (a type of epilepsy) and diabetic neuropathy in the near future, with the trade name Vimpat.
Before lacosamide can be officially approved for fibromyalgia it needs to go through more trials and it would take until the end of next year at the earliest before it could receive approval for this indication. Of course, even if it is not approved for fibromyalgia, doctors can still prescribe it off-label for fibromyalgia (and CFS/ME) once it is approved for use in another condition. If/when lacosamide is approved, more information about it will be posted here.
18th June 2008
The SNRI antidepressant duloxetine (Cymbalta, p. 124) has been approved as a fibromyalgia treatment by the FDA, making it the second drug approved for this purpose after pregabalin (Lyrica, pp. 78-79) - just like predicted in the book. This is obviously good news, though it does not mean that duloxetine is actually a better drug for fibromyalgia than e.g. the other SNRI antidepressants venlafaxine (Effexor, pp. 123-124) and milnacipran (Ixel, pp. 124-125). It only means that the manufacturer wanted to invest in the appropriate studies to gain FDA approval for this use, which isn't cheap at all.
It remains to be seen whether the third officially approved drug will be sodium oxybate (Xyrem, p. 32), milnacipran, flupirtine (Effirma, p. 64) or something else. The FDA is still considering Hemispherx Biopharma's NDA for Ampligen (pp. 215-216) as the first official CFS/ME treatment.
15th June 2008
An interesting new study will be published in European Journal of Internal Medicine titled "Efficacy of Raloxifen in treatment of fibromyalgia in menopausal women." In the study ralofixene was found superior to placebo. It improved both pain and fatigue. Raloxifene is a selective estrogen receptor modulator (SERM) and is, of course, featured in the book (p. 280), but this is the first study done of its use for fibromyalgia (no studies in CFS/ME have been done).