Fibromyalgia - Emerging treatments | BMJ Best Practice US

Central neurostimulatory therapies (device therapy)

An exciting development in the pain field that is being partially led by work in fibromyalgia (FM) is the explosion of interest and knowledge in the use of central neurostimulatory therapies in fibromyalgia and related conditions.[175][176] [ ] [ ] These therapies, which include transcranial direct current stimulation and magnetic stimulation, may reduce pain and improve a number of other domains in fibromyalgia; in some cases, the effect of therapy has lasted well after the cessation of treatment.[177][178][179][180] Further research is needed.

Low-dose naltrexone

When used at lower doses, naltrexone (an opioid antagonist) is thought to paradoxically decrease pain due to an increase in the release of endogenous opioids. It may also have anti-inflammatory properties. One systematic review concluded that low-dose naltrexone may be an alternative treatment for patients with chronic pain conditions.[181] One small randomized, double blind, placebo-controlled, crossover trial included in the review specifically for fibromyalgia patients, reported that low-dose naltrexone significantly reduced pain compared with placebo.[182]

Cannabinoids

Although there are no cannabinoids approved for use in chronic pain in the US, this class of drugs has displayed efficacy in both fibromyalgia and other chronic pain conditions.[183] Evidence from subsequent systematic reviews found insufficient, high-quality evidence of benefit for medical cannabis in patients with fibromyalgia; however, emerging data suggest a positive effect.[184][185][186][187] There is uncertainty regarding the optimal dose and ideal cannabidiol (CBD)/tetrahydrocannabinol (THC) ratios.

Ketamine infusions

In addition to the serotoninergic and noradrenergic neurotransmitter systems, the glutaminergic system is also clearly involved in fibromyalgia and more broadly in pain sensation, as evidenced by the fact that an intravenous ketamine infusion seems to be predictive of subsequent responsiveness to dextromethorphan in fibromyalgia but is not efficacious itself as long-term therapy.[188]

Memantine

The efficacy of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is being assessed for the treatment of chronic pain in patients with FM. One systematic review reports that evidence regarding the use of memantine for chronic pain is limited and uncertain.[189] Despite its potential, pain relief achieved in clinical studies is small and is associated with an increase in dizziness; therefore, no clear recommendations can be made about its routine clinical use until larger and more definitive studies are conducted.[189]

Selective serotonin-reuptake inhibitors (SSRIs)

Studies have found varying effects of SSRIs on pain in patients with FM, suggesting that the benefits of selective-norepinephrine reuptake inhibitors (SNRIs) might be derived from the increased norepinephrine rather than serotonin. SSRIs are not recommended for treatment of pain, sleep disturbance, or fatigue in the EULAR guidelines.There have, however, been reports that using an SSRI together with a tricyclic antidepressant can be helpful in fibromyalgia.[147]

Esreboxetine

A highly selective norepinephrine reuptake inhibitor that has been studied in preclinical pain models and is being investigated for use in fibromyalgia. A blinded, placebo-controlled study of 267 patients showed that the esreboxetine group had statistically significant improvement compared with placebo with respect to weekly average pain, and that more patients in the treatment group reported a >30% pain reduction (37.6% vs. 22.4%). Improvements were also seen in quality of life and functional measures.[190]

Mirtazapine

Mirtazapine, a tetracyclic antidepressant, has been demonstrated a clinically relevant reduction in pain (30% or greater), reduction of mean pain intensity, and sleep problems compared with placebo in adults with fibromyalgia.[191] Somnolence, weight gain, and elevated alanine aminotransferase were more frequent with mirtazapine than placebo.[191]

Melatonin

Melatonin, a neurohormone, has been shown to have several positive effects on patients with FM, including improvement of sleep quality, pain, and disease impact.[192] Compared with other agents such as duloxetine, no major adverse events were reported following treatment with melatonin consumption.[192] Further research is needed

Transcutaneous electrical nerve stimulation (TENS)

One Cochrane review concluded that there is insufficient high-quality evidence to support or refute the use of transcutaneous electrical nerve stimulation (TENS) for fibromyalgia.[193] One subsequent randomized controlled trial (RCT) reported that in women with fibromyalgia who were on a stable medication regimen, 4 weeks of active TENS significantly improved movement evoked pain compared with placebo TENS or no TENS.[194]

Vagus nerve stimulation (VNS)

One phase 1/2 proof of concept trial in patients with treatment refractory fibromyalgia reported that of the 12 patients that completed the trial, five patients achieved the efficacy measure (a composite measure; reduction in pain, improvement of overall wellness, and physical function) at 3 months, with two patients attaining the secondary outcome of no longer experiencing the widespread pain or tenderness criteria necessary for the diagnosis of fibromyalgia.[195] The effect appeared to increase over time, with additional patients attaining both criteria at 11 months.

Acupuncture

A review of randomized trials of traditional Chinese medicine (TCM) treatment for fibromyalgia (including not only acupuncture but also TCM modalities of herbal medication and cupping) suggested that these therapies seem to be effective, but trials are limited by insufficient methodologic rigor.[196] A subsequent systematic review reported that invasive techniques (including acupuncture and dry needling) significantly decreased pain, improved the pain pressure threshold and quality of life.[197] One Cochrane review found that the use of electroacupuncture might be more effective than manual acupuncture (not involving electrostimulation).[198]

Biofeedback

Derangement of the autonomic nervous system has been proposed to account for some of the symptomatology in patients with fibromyalgia. Heart rate variability (HRV) biofeedback training, which teaches the patient to breathe at a resonant frequency, can help decrease sympathetic overdrive and perhaps reduce pain. There is a very small amount of evidence to suggest that there was decrease in pain and depression and increase in functioning after 10 weekly sessions of HRV biofeedback training.[199] Electromyography (EMG) biofeedback has been shown to be modestly helpful in decreasing pain in a small study of poor design.[200] Further research is warranted.

Herbal/supplement medications

Some evidence suggests potential benefit from magnesium, L-carnitine, coenzyme Q10, and S-adenosylmethionine, although firm conclusions cannot yet be drawn on the benefits of these or other supplements.[201][202][203]

Homeopathy

One systematic review of trials on homoeopathy for symptom reduction in fibromyalgia found three placebo-controlled randomized controlled trials that suggested benefit from the use of homeopathy, although more research is needed.[204]

Hydrotherapy

More commonly used in European countries, hydrotherapy, or the use of water for therapeutic purposes, has been studied for fibromyalgia in small trials. Balneotherapy (bathing in warm or cold medicinal water or mud) or spa therapy (bathing in mineral water) are forms of hydrotherapy. A meta-analysis found studies of hydrotherapy in fibromyalgia to be of small size and poor quality, but suggested that hydrotherapy may result in modest short-term reductions in pain for patients with fibromyalgia.[205] A further review of hydrology treatment concluded that evidence is limited and further clinical trials are needed for each relevant application.[206]

Manual therapies

There is moderate evidence for massage therapy and limited evidence of poor quality for spinal manipulation to help patients with fibromyalgia.[207][208][209][210]

Qi Gong

Qi Gong is a martial art therapy that is part of traditional Chinese medicine. Little evidence is available, but in one study patients demonstrated dramatic reductions in pain and improvements in functioning.[211]