Chapter 18 ● Treatment of ME/CFS

Medicine is not only a science; it is also an art. It does not consist of compounding pills and plasters; it deals with the very processes of life, which must be understood before they may be guided.

– Paracelsus, 1531

F I B R O M Y A L G I A – Regarding treatment, the disease presentation, physician specialty and vision of the world, clinical experience, and peculiar perspectives impact the approach. Under conventional Western medicine, for instance, fibromyalgia patients are managed quite differently from other ME|CFS patients.

For rheumatologists, orthopedists, physiatrists, and algologists, fibromyalgia is a chronic painful disease treated with drugs, physiotherapy, and other conventional resources. Still, these are almost always palliative treatments, focusing on the primary symptoms – pain, fatigue, depression, and sleep problems.

Most available treatments result from trial and error; pretty often, everything has been tried, and no therapy consensus has been possible. The extreme susceptibility to drug reactions ME|CFS patients present makes it always dangerous to try new medications. The pharmacologic resources to control symptoms in FMS patients are summarized below:

Steroids?have no place in fibromyalgia therapy; those can be deleterious and rarely prescribed.

Non-steroidal anti-inflammatory?(NSAID) substances such as ibuprofen, diclofenac, nimesulide, naproxen, and others are generally ineffective.

Painkillers.?Among regular pain relievers – except for high-dose dipyrone (Novalgina?), a drug unavailable in the US and that must be carefully given to patients with low blood pressure – are never helpful, not even for mild pain. Aspirin and paracetamol are also ineffective, and higher doses are not recommended for their potential hazards.

Opioids.?Although excessively prescribed, morphine, codeine, oxycodone, other hypnotics and narcotics are not beneficial; most induce dependence and have been just eventually useful for pain control. Countless patients become dependent on those drugs.

Benzodiazepines?have been traditionally given to almost all patients to mitigate anxiety and sleep problems. Drugs such as diazepam (Valium?), lorazepam (Lorax?), and clonazepam (Rivotril? or Klonopin?) may be somewhat valuable for patients with restless leg syndrome or severe sleep problems.

Tricyclic compounds?such as cyclobenzaprine (Flexeril?) and amitriptyline (Elavil? or Triptanol?) ease depression, migraines, and body pain in 40% of patients.

Selective Serotonin Reuptake Inhibitors?(SSRIs) are antidepressants usually prescribed by physicians, especially by rheumatologists, treating FMS. The most often used are fluoxetine [Prozac?]; paroxetine [Paxil? or Aropax?], and sertraline [Zoloft?].

Dual reuptake inhibitors, especially venlafaxine [Effexor?], duloxetine [Cymbalta?], and tramadol [Ultram? or Tramal?], are said to alleviate pain and depression. Tramadol, however, induces nausea in a substantial number of patients demanding antiemetics such as Scopolamine [Transderm SCOP?], Dolasetron [Anzemet?], Granisetron [Kitrill?], meclizine [Antivert?], Palonosetron [Aloxi?], and Ondansetron [Zomax?, Vonau?]; this lat one recently associated to arrhythmias according to FDA. Other drugs such as bromopride, phenothiazines, and substitute benzamides are also frequently used.

Neurontin? (gabapentin) and Lyrica? (pregabalin) represent a relatively new class of anti-epileptics said to be effective in controlling neuropathic pain and paresthesias and improving cognitive disorders. Soon after their debut, these drugs were tried in fibromyalgia and related syndromes, with variable, sometimes favorable results, according to doctors. However, this is not precisely what patients say.?

In 2007, Lyrica? was turned into the first FDA-approved drug for fibromyalgia; one year later, Cymbalta? (duloxetine) became the second. In January 2009, the FDA approved Savella? (milnacipran), the third. Lyrica?, Cymbalta?, and Savella? are said to mitigate pain and improve function and life quality in some fibromyalgia patients. My personal experience with the first and second drugs is not favorable. I see high LDH and liver enzymes in 20% of patients with minimal responses. Lyrica? seems to be preferable over Cymbalta? for the majority of patients who tried both. I never prescribed Savella?.

Collateral effects of Lyrica? include blurred vision, somnolence, ponderal gain, dizziness, trouble concentrating, excessive swelling of the feet and hands, and dry eyes and mouth. Allergic reactions are uncommon. The side effects of Cymbalta? are similar but include nausea, constipation, low appetite, and sweats. The drug may lead to suicidal ideation and behavior.

Savella? was the first and still is the only drug introduced primarily for fibromyalgia. Although not listed as an antidepressant, its mechanism of action is similar to medicines used to treat psychoses and depression. Like duloxetine, but especially on withdrawal, Savella? induces suicidal thoughts. Other undesired effects are dizziness, gastrointestinal complaints and vomiting, palpitations, tachycardia, dry mouth, and high blood pressure.

While pain has a strange behavior in fibromyalgia, the mechanism of action of these drugs remains unknown. Data from research suggest these drugs modulate the release (or actions) of neurotransmitters involved in pain control in the CNS. The drugs mentioned above are approved for adults; safety for breastfeeding is not established.

Cannabinoids.?From patients' perspectives, cannabis-derived medicines are the most effective therapy, confirmed by the related experiences in stuffthatworks.health. Although I have prescribed cannabidiol for some ME|CFS patients, when medical cannabinoids became approved and widely available, I had already finished the research, and most patients had been referred to other physicians. Still, the limited experience with these substances was very favorable.?

Addressing Comorbidities –?Although primary fibromyalgia is common, it is?a?comorbidity in most patients, often affected by other diseases or conditions. Treatment of other issues may harm people with fibromyalgia. Antibiotics, antifungal, antivirals, antineoplastic, cardio and psychoactive, neurological, and other medications may impact symptoms and worsen FMS.

Although not adequately studied, adjuvant and alternative therapies are recommended by some and used by many. These include medications such as melatonin (orally given, 5 to 10 mg at night is hypnotic for some patients). Besides, other treatments based on massotherapy, phytotherapy, myofascial release, psychotherapy, acupuncture, and other treatments have been extensively tried in ME|CFS or fibromyalgia.

Other reasonable recommendations for?fibromyalgia?patients are good habits and nutrition; sleep hygiene; discipline and routines; relaxation and meditation; self-education (such as provided by The National Fibromyalgia Association); and participation in support groups.

In the past, and still today, some advocate Cognitive Behavioral Therapy (CBT) and moderate aerobic training regularly; however, no benefit has been demonstrated for both in fibromyalgia.

The management of the disease is a frustrating experience for physicians and their patients; refractoriness to medications and most forms of therapy is a rule, and disabling symptoms are resistant; nevertheless, some experts claim to achieve reasonable response rates under empiric treatments.

Many healthcare professionals do not believe that ME|CFS is an organic disease, and various approaches to treating it as a psychosomatic condition have been unsuccessful. So far, there is no published gold standard, no consensual treatment protocol, no optimal regimen, or recognized best drugs; regretfully, most patients are just superficially treated, very often without a consistent diagnosis.

Going through the web, I have found an almost infinite number of treatment plans and valuable substances. Besides, anecdotal recommendations, alternative medicine, personal experiences, suggestions, auto-medication, stimuli, tonics, and clinical trials are based on excessive or complex theoretical explanations or inconsistent beliefs. My own previous experiences with most proposed treatments were genuinely disappointing.

Again, though sometimes conflicting with scientists, the information directly obtained from a large cohort of patients and consolidated in a single database provided the most trustworthy information about symptoms and responses to all available treatments. Eight years ago, curetogether.com consolidated this information; before I had the data directly obtained from ME|CFS and FMS victims, let us see what experts have been doing.

Symptoms Relief.?Like for fibromyalgia patients, drugs addressing pain, depression, emotional lability, hypersensitivity, anxiety, and panic are often used in ME|CFS; being essential to consider, however, that all treatments can be in vain. Some claim that symptomatic therapy can backfire on the most affected patients. All painkillers have been prescribed; still, some patients need opiates and local pain blockades. Hospitalization is often necessary. Most large hospitals got Pain Centers; 70% of their patients got ME|CFS-related pain.

As for FMS patients, selective serotonin reuptake inhibitors (SSRIs) are prescribed to control swinging mood and depressive states, with poor results. These drugs include citalopram (Celexa?), escitalopram (Lexapro?), fluoxetine (Prozac?, Prozac Weekly?, and Sarafem?), paroxetine (Paxil?, Paxil CR?, Aropax?, Pexeva?), sertraline (Zoloft?] and the anti-psychotic olanzapine (Symbyax?).

Also, just like for FMS patients, the selective serotonin and norepinephrine reuptake inhibitors (SNRIs), venlafaxine (Effexor?), duloxetine (Cymbalta?), and tramadol (Ultram? and Tramal?) are used for pain and depression. Tramadol induces nausea in a substantial number of patients, requiring antiemetics. For all these drugs, outcomes are rated unacceptable by most patients.

All benzodiazepines have been prescribed for ME|CFS patients, but among those drugs, clonazepam (Rivotril? or Klonopin?) is the most used and probably the most valuable to control anxiety and mitigate insomnia; nevertheless, other substances with hypnotic properties such as melatonin, gabapentin (Neurontin?), and quetiapine are often required. Gabapentin is most used to control neuropathic pain, and its role in ME|CFS pain is not established.

Dietary changes?are generally focused on improving GI affection and reducing inflammation. Elimination of sugars and sweeteners; or removal of food known to worsen symptoms or induce allergy are common approaches. Many advocated soy-enriched diets; some restrict milk and lactose, others restrict animal protein, red meat, or fats; some restrict natural fruits; others impose a tight diet. Nutritional supplementation and digestive enzymes are often prescribed. Salt restriction is claimed to be helpful for those presenting severe headaches. Lactase deficiency is common among ME|CFS and demands lactose restriction. Gluten intolerance imposes blood tests, but a trial of a gluten-free diet is advised for most patients.

Vitamins and antioxidants.?It seems consensual that these are good for most disease victims; many patients are placed in high-dose supplementation with all kinds of vitamins, amino acids, oligo-elements, minerals, and antioxidants such as astaxanthin, racetocopherol, coenzyme Q10, gluthation, astaxantin, omega 3, omega 6, and omega 9.

Exercises.?Most physicians believe moderate activity is necessary; some prescribe unique and detailed exercise regimens. Nevertheless, very few patients believe physical activity improves their clinical condition; some cannot keep on any exercise; most get worse with physical activity.

Antiviral drugs.?All clinically relevant herpesviruses, HSV, VZV, CMV, HHV6, and EBV, have been implicated in ME|CFS. For this reason, acyclovir, valacyclovir, gancyclovir (and even valganciclovir) are prescribed for many patients without benefit. Other antivirals, such as tenofovir and lamivudine, designed for HIV, have been tried under the belief that these drugs could be effective against other retroviruses (such as XMRV) implicated in ME|CFS, but no real benefit was found. Fifteen years ago, a promising experimental drug named ampligen was tried, with no proven results.

Ribavirin, a toxic drug effective against RNA viruses, has been tried in ME|CFS, with no definite results; its combination with interferon did not improve patients said to be infected with coxsackie B virus. However, some patients with real postviral fatigue are often mistakenly diagnosed as ME|CFS, and these patients could achieve some clinical improvement with antivirals, but this is not proven.?

Hormones.?Endocrine dysfunction is said to be extensive and very common, often requiring treatment. When thyroid and other endocrine dysfunctions are suspected or demonstrated, drugs are needed. DHEA has been prescribed for patients with low SDHEA or low testosterone.

Immunomodulators, antibiotics, vaccine boosts, and immunoglobulins?are prescribed for those with recurrent infections.

Diuretics.?According to some, furosemide and acetazolamide help mitigate headaches.

Beyond these measures, countless unusual treatments have been created; formulated sports food, hydrotherapy, magnesium (generally as glycinate, but also magnesium chloride), and many others. Calcium channel blockers have been prescribed for patients with cardiovascular symptoms and hypertension.

Psychoanalysis and psychotherapy?are often needed and prescribed for most patients.

Antineoplastics.?On edge, drugs for cancer have been tried in ME|CFS. Rituximab, a drug that depletes CD20+ B lymphocytes, failed to improve patients.

B E Y O N D.?The most careful physicians demand more for their ME|CFS patients. The disease is so extensive that a more holistic approach is needed, and through this path, it is crucial to focus on the known main disease components:

1. Improve nutrition and immunity

2. Treat infections

3. Control anxiety

4. Recover sleep quality

5. Reduce inflammation

6. Restore intestinal integrity, function, and microbiome

7. Adjust endocrine dysfunction

8. Remove toxins and metals

9. Reduce medicines

Chapter 19 >>