Because new research is constantly coming out, new medications are approved and sometimes old ones are withdrawn from the market, this page will include any updates and possible corrections to Reviving the Broken Marionette. The numbers in parentheses after the name of the medication refer to the page numbers in the book that discuss the drug.

If you have noticed an error in the book or are aware of any new data that has come out since its publication, please contact the author at book@brokenmarionettebook.com. Please list any sources for your information. You will be credited for the information, but only if you specifically request to.

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23rd April 2012

A new double-blind, placebo-controlled study of Ampligen (now named rintolimod, pp. 215-216) was published in PLoS One. In it Ampligen was tested speficially in "severe cases of chronic fatigue syndrome" and was found fairly effective and well-tolerated.

Many new fibromyalgia studies have been published, though nothing groundbreaking. A double-blinded placebo-controlled study published in Arthritis and Rheumatism found esreboxetine (an analogue of Reboxetine/Edronax, pp. 125-126) effective for fibromyalgia pain, with no significant differences among tested doses. Physical functioning, however, did not improve.

A new study was published on sodium oxybate (Xyrem, pp. ) for fibromyalgia in Annals of Rheumatic Diseases. Like the several previous studies it found that Xyrem both reduced pain and improved sleep quality compared to placebo. Another thoroughly tested but expensive fibromyalgia treatment, growth hormone (pp. 203-204), was again found effective in a new study, published in Pain.

In a study published in Rheumatology International oral magnesium citrate was also found effective for fibromyalgia, reducing tender points and depression. When it was combined with amitriptyline (Elavil, pp. 113-114) it was found even more effective.

30th October 2011

The XMRV issue is a real mess and I won't be touching it in this update, since I've never felt the presence or absence of XMRV (or another retrovirus) as a causative or non-causative agent affects current treatment in any way.

The new study, the second of its kind, of rituximab (Rituxan) for CFS/ME (published in PLoS ONE) has gathered a lot of press, but I feel it is a step in the exactly wrong direction. The best CFS/ME treatments are all immunostimulants. Immunosuppressants may appear to help, but only worsen the underlying immune dysfunction in the long run. (The same goes for autoimmune diseases, too.)

The first study on the muscle relaxant cyclobenzaprine (Flexeril, pp. 35-36) on fibromyalgia will be published in Journal of Rheumatology. Cyclobenzaprine resembles tricyclic antidepressants and has widely been used in fibromyalgia. In the study it improved sleep and reduced pain, tenderness, fatigue and depression compared to placebo. A new study, in BMC Musculoskeletal Disorders, found another antidepressant traditional used in fibromyalgia, trazodone, useful for pain, sleep and depression, especially when combined with pregabalin. A study in Open Rheumatology Journal found that pregabalin (Lyrica) helped many patients who weren't helped by several other medications - including the older and cheaper, but very similar anticonvulsant gabapentin (Neurontin). This is interesting because it is the first paper attempting to show that pregabalin may actually in some ways be superior to gabapentin - or at least they may help different people (perhaps gabapentin could help some people not helped by pregabalin).

There is also a new study of melatonin published in the Journal of Pineal Research, which found melatonin (pp. 30-31) either alone or combined with fluoxetine (Prozac, pp. 119-120) effective for treating fibromyalgia.

9th February 2011

New study published in the Open Rheumatology Journal on pregabalin (Lyrica, pp. 78-79) found it effective for "treatment-refractory" fibromyalgia patients. What makes this result interesting that these patients had already received tricyclic antidepressant, other medications - and gabapentin (Neurontin. pp. 77-78) which is extremely similar to pregabalin. As such it suggests that patients who have not benefited from Lyrica can still benefit from Neurontin.

26th December 2010

There are some new fibromyalgia and CFS/ME treatment studies. A study to be published in European Neuropsychopharmacology compared the antipsychotic amisulpride (Solian, p. 139) and the antidepressant fluoxetine (Prozac, pp. 119-120) in non-depressed CFS/ME patients. Amisulpride was found much more effective while interestingly it did not improve mood or anxiety, perhaps because the participants were not depressed. Both drugs were equally well tolerated. This is the first study done of amisulpride (which despite being an antidepressant is frequently used for depression as well) in either CFS/ME or fibromyalgia. Amisulpride is not available in the United States or Canada.

In a study published in Journal of Pineal Research melatonin (Transzone, pp. 30-31) by itself or in combination with fluoxetine was compared to fluoxetine alone in the treatment of fibromyalgia and was found effective (however, the abstract is not very specific and the full text is not available).

1st December 2010

The (dextro)propoxyphene-containing painkillers Darvon and Darvocet (pp. 57) have been pulled from market in the U.S. because their risks were considered to outweigh its benefits. (Dextro)propoxyphene had already been withdrawn in the European union for the same reasons. They used to be prescribed for fibromyalgia quite frequently, but are considered to have low efficacy and high risks compared to other narcotic painkillers. Another fibromyalgia/CFS/ME drug whose use has recently been limited is modafinil (Provigil, pp. 161-162), the use of which the European Medicines Agency has decided to restrict to narcolepsy. Thus depending on the legistlation it may now be illegal (or at least difficult) to prescribe modafinil for fatigue in CFS/ME and fibromyalgia in some European countries.

New XMRV studies continue to be reported in conferences and hopefully also published soon. Some yet-to-be-published data suggests that rintolimod (Ampligen, pp. 222-223) may be more effective in patients who are XMRV-positive than those who are XMRV-negative - which is curious considering Ampligen has also demonstrated activity against herpesviruses.

The first study of esreboxetine (S-reboxetine) which is essentially the same drug as reboxetine (Edronax, pp. 125-126) for fibromyalgia was published in Clinical Therapeutics. Reboxetine is an antidepressant which only affects norepinephrine (noradrenaline) reuptake. It is not considered a very effective drug for depression, but in this study it was moderately helpful for pain, fatigue and functionality. The study was randomized, double-blind and placebo-controlled with a fairly large number of patients, but only lasted for eight weeks, which somewhat diminishes its usefulness.

Somewhat peculiarly a recent study published in Rheumatology (Oxford) found that eight weeks of hormone replacement therapy (HRT) with transdermal estradiol (estrogen, pp. 200-201) did not improve pain in postmenopausal women with fibromyalgia. Estrogenic drugs are generally thought to be helpful in fibromyalgia and are sometimes used even in premenopausal patients.

There is a new double-blinded placebo-controlled study on dolasetron (Anzemet) in European Journal of Pain which found it effective for pain, but improvement in other symptoms failed to reach statistical significance. That dolasetron may help fibromyalgia is not very surprising, considering that the other 5-HT3 antagonists (granisetron, ondansetron and tropisetron, pp. 259-260) have already been shown to be effective.

28th September 2010

The XMRV debate is still raging, with several new negative studies published, but also strong positive research emerging. No one knows the full role of XMRV in CFS/ME (or other diseases yet), but the WPI and some other institutions are doing their best to crack the puzzle. In the meanwhile, XMRV or not, we still have dozens of effective treatments.

A new study of the use of trazodone (Desyrel, pp. 131-132) in fibromyalgia has been published in BMC Musculoskeletal Disorders. This antidepressant has been used to treat CFS/ME and fibromyalgia for a long time, even though it is known not to be an effective analgesic like many antidepressants, but it often improves sleep. This study showed a good effect on sleep and also some effect in general symptomalogy, anxiety and depression. Unexpectedly tachycardia (rapid heartbeat) was the most frequently reported side effect.

Diabetes drug rosiglitazone (Avandia, p. 275) has been withdrawn from market in Europe and its use will be severely restricted in the United States due to increased risk of cardiovascular events. The very similar drug pioglitazone (Actos, 275) can be used in its place. These drugs are sometimes (not often) used to treat autoimmune diseases and to reduce the side effects of antibacterial treatment in chronic infections.

12th January 2010

There has been a lot of buzz on the CFS/ME front. A British research group could not replicate WPI's XMRV findings, which led some people to dismiss them (and CFS/ME as a whole) as humbug. Simon Wessely who fronts the group has dedicated his life to "proving" that CFS/ME is a psychiatric/psychosomatic illness and the "diagnostic criteria" he uses in his studies makes it certain that actual CFS/ME patients cannot participate. Also, even if the study was done on real CFS/ME patients, it could merely show that a) they are not doing lab work correctly (as WPI suspects) or that b) XMRV is not nearly as common in Europe as it is in the U.S., and that in Europe CFS/ME is mainly caused by other viruses. Luckily, several other research groups are doing XMRV research as well and we will have real, trustworthy data about XMRV's role in CFS/ME soon.

In another new twist a Japanese research group claims to have a possible new blood test for CFS/ME. What makes this peculiar is that they claim people with CFS/ME have significantly elevated levels of a protein called alpha-MSH in their blood. While there is no published research about this, several doctors have claimed the contrary: that alpha-MSH levels are unusually low in CFS/ME. There is even a patent suggesting MSH (which is not commercially available) as a treatment for CFS/ME. Again, more research will be needed to see who is right, but it looks like the different doctors have been looking at different illnesses or different subgroups of CFS/ME.

A study published in Psychiatry Investigation found the cholinergic drug galantamine (Reminyl, p. 238) moderately helpful for CFS/ME. It also lowered DHEA levels, which in study were found to be elevated in the CFS/ME population. Curiously most previous studies have found DHEA levels in CFS/ME to be low and this hormone is also commonly used as a treatment for CFS/ME (pp. 202-203). This is not the first study to evaluate galantamine in CFS/ME; of the previous studies one got good results and the other one did not, but it was using very low doses.

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