Fibromyalgia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Fibromyalgia (FM) can be managed but not cured. The goals of treatment are to manage the core symptoms of FM by reducing pain levels, improving the quality of life and function, improving sleep quality and reducing fatigue, improving physical and mental health, and improving cognitive function.[122] Treatment should include both non-pharmacological and pharmacological therapies, alone or in combination, which is individualised to the patient and involves a multidisciplinary team.[122]

There is evidence to suggest that symptoms of FM differ between male and female patients with fibromyalgia.[5][6][123] The efficacy and safety of pharmacological and non-pharmacological interventions for fibromyalgia have not been adequately evaluated in men as most clinical trials have predominantly enrolled women. More research is needed to understand the sex-specific aspects of fibromyalgia and to optimise its diagnosis and treatment in both men and women. See Case history (Other presentations).

All patients benefit from non-pharmacological therapy with pharmacological interventions introduced using a stepwise approach. However, patients with very severe symptoms may require both non-pharmacological and pharmacological therapies as initial treatment.

Individualised treatment

In practice, before starting treatment, it is useful to assess patients with the revised fibromyalgia impact questionnaire (FIQR).[124] While primarily a research tool, this instrument assesses disease impact over three domains (function, overall impact, and symptoms) and probably gives a better reflection on symptom impact (minimal, moderate, and severe).

FIQR disease severity scores that can be used in practice are:[125]

Remission ≤30
Mild severity >30 and ≤45
Moderate severity >45 and ≤65
Severe severity >65

The initial score can guide how aggressive initial therapy should be (patient education for mild severity vs. multidisciplinary therapy for more severe impact) and also gives more of an 'objective' way to follow response to therapy as most patients are mainly focused on pain early in the treatment course. It also can help less experienced clinicians following patients long-term.

Non-pharmacological therapies

Non-pharmacological therapies are the cornerstone to the management of fibromyalgia, but they are often underutilised in clinical practice. [ ] There is strong evidence that demonstrates short-term positive effects of non-pharmacological conservative therapies in people with fibromyalgia. Multimodal conservative therapies also could provide benefits in the medium- and long-term.[126]

Patient education and self-management

Once diagnosed with fibromyalgia, patient education is considered to be the first step in self-management, which can be effective in improving physical function and reducing pain in the short- and long-term for fibromyalgia.[127][128][129] See Patient discussions.

Randomised controlled trial evidence has demonstrated that a self-management patient education programme for fibromyalgia syndrome improved disease and treatment-specific knowledge at discharge (6-12 months), subjective knowledge, pain-related control, self-monitoring and insight, communication about disease, action planning for physical activity and treatment satisfaction for inpatients with fibromyalgia, compared with usual care education in inpatient rehabilitation.[130]

There is growing evidence that patients who are obese present with more severe symptoms of fibromyalgia and lower levels of quality of life, and that a higher weight negatively impacts treatment outcomes.[123][131][132][133] Therefore, weight management should be encouraged in patients with fibromyalgia.[133]

Physical activity

Any exercise regimens undertaken should be individualised to the patient. In practice, patients should be warned that pain and fatigue may transiently worsen as they begin to exercise. This can be mitigated by 'starting low, going slow' (progressively increasing intensity/duration over weeks to months), but short bursts of high intensity exercise may suit some patients. Reasonable goals include 2-3 sessions of aerobic exercise (lasting 20-30 minutes each) and 2-3 sessions of resistance training (≥8 repetitions per exercise), recognising that not all patients can achieve this goal. Some patients may experience prolonged post-activity exhaustion/malaise and may benefit from activity pacing, akin to recommendations for patients with chronic fatigue syndrome/myalgic encephalitis. See Myalgic encephalomyelitis (Chronic fatigue syndrome).

Many patients would likely benefit from a referral to physiotherapy to discuss low-impact exercises.

Many types of physical activity that combine exercise and relaxation have been shown to be helpful at reducing pain, anxiety, depression, and fatigue, and at improving sleep quality, functional capacity, and quality of life.[122][134][135][136][137][138][139][140][141][142][143] [ ] [ ]

One meta-analysis proposes that the mechanism of pain should be considered when considering exercise interventions for patients with fibromyalgia. They suggest that moderate intensity global exercises performed for a long period of treatment may benefit patients with nociplastic pain predominance, and focused and intense exercises for a short period of treatment should be performed in patients with nociceptive pain predominance.[144]

Psychological interventions

Evidence has demonstrated the efficacy of cognitive behavioural therapy (CBT) to reduce symptoms of chronic pain.[122][145] One Cochrane review concluded that CBT has a small or very small beneficial effect, compared with control interventions, at reducing pain, disability, and distress caused by chronic pain in adult patients with chronic pain.[145]

A subsequent systematic review of psychological interventions for women with fibromyalgia (including CBT and behavioural therapy, coping strategies training, mindfulness, acceptance and commitment treatment, hypnosis, meditation, music therapy, short-term psychodynamic psychotherapy, and writing emotions) reported that the majority of psychological interventions improved the quality of life and reduced the symptoms of fibromyalgia in women.[146]

Internet-based programmes incorporating education, CBT, biofeedback, and exercise can be effective in fibromyalgia, particularly for those patients unable to access personal or group provision of CBT.[147]

Pharmacological therapies

Pharmacological therapy is, at best, modestly effective in a minority of patients. One network meta-analysis concluded that the benefits of pharmacological treatment in patients with fibromyalgia are of questionable clinical relevance.[148] There is strong evidence that demonstrates the positive effects of non-pharmacological conservative therapies in the short-term in patients with fibromyalgia, and that multimodal conservative therapies could provide benefits in the medium- and long-term.[126] This should not deter treatment with pharmacological therapy, but demonstrates the importance of non-pharmacological and multimodal treatments.

Treatment choice and stepwise titration

Choice of pharmacological treatment should be guided by individual patient symptoms. For example, a serotonin-noradrenaline reuptake inhibitor (SNRI) is a good first choice when the patient suffers from comorbid depression or fatigue, whereas a gabapentinoid may be preferred when the individual is experiencing significant comorbid sleep issues.

In practice, pharmacological treatment may be initiated with a subtherapeutic dose to look for signs of adverse effects. The medication is then slowly titrated up (usually over weeks) to a minimum target dose. If symptoms improve, titration up to the maximum dose, or the maximum tolerated dose may be considered. If a suboptimal response is achieved or dose titration is limited by adverse effects, a combination of two or more different drug classes (e.g., an SNRI with a gabapentinoid, or an SNRI with a tricyclic antidepressant) could be trialled.[149][150][151] The aim is to use the lowest dose which gives the best therapeutic outcomes with minimal adverse effects (most trials report a 30% reduction in pain intensity). This is quite objective and is usually determined with the patient. Medications should be taken for a minimum of 12 months; however, they are often taken longer. Treatment should be withdrawn if a patient develops intolerable adverse effects, or if no improvement of symptoms is seen after at least 3 months.

Tricyclic antidepressants

Meta-analyses suggest that a meaningful clinical response can be expected in about 30% of patients with fibromyalgia treated with tricyclic antidepressants.[152][153][154] However, there is no good evidence showing extension of benefit beyond 8 weeks.[155] If no benefit is seen after a trial of 6 weeks, the medication can be stopped. If the medication was initially effective but seems to have decreased efficacy, it can be temporarily discontinued and restarted.

Examples of drugs within this class include amitriptyline and cyclobenzaprine (a skeletal muscle relaxant with a similar structure to amitriptyline that has similar effects to tricyclic antidepressants). Amitriptyline is often used in preference over cyclobenzaprine due to its additional benefit on mood and lower risk of adverse effects.

The anticholinergic adverse effects of tricyclic antidepressants often limit their tolerability, especially in older patients; however, one benefit is that they can improve sleep.

SNRIs

The SNRIs duloxetine and milnacipran are effective in the treatment of fibromyalgia.[122][156] Both SNRIs have been shown to reduce weekly pain scores in patients with fibromyalgia compared with placebo.[157][158][159][160][161][162] [ ] Duloxetine and milnacipran are both approved for the treatment of fibromyalgia.

Duloxetine has demonstrated comparable efficacy for the treatment of fibromyalgia compared with amitriptyline, only differing due to patient symptom profile, that is high-quality evidence suggests that duloxetine is more effective for patients experiencing mood disorders.[163] One long-term safety study reported a 50% reduction in pain in 40% of women treated with duloxetine, with a favourable risk/benefit profile for at least 12 months for the management of fibromyalgia.[164]

Tolerability of these drugs can be increased by warning patients of the risk of nausea and assuring them that in most cases this is transient, and by starting the drug at a low dose and increasing the dose slowly. Gastrointestinal distress, hyperhydrosis, and headache are the most commonly reported adverse effects with milnacipran.[158][162][165] The most common adverse effects of duloxetine are nausea and headache.[166][167]

Gabapentinoids

The efficacy of pregabalin has been demonstrated extensively, and it is approved for the treatment of fibromyalgia.[168] [ ] Gabapentin is similarly effective, but it is not approved for the management of this condition and has less evidence to support its use.[169]

These drugs have analgesic properties as well as anxiolytic and anticonvulsant activity.[170] Meta-analyses support use of either of these agents, reporting pain reduction, improved sleep, and improved health-related quality of life.[171][172] [ ] [ ]

In practice, the adverse effects of gabapentin increase as the dose increases, while the adverse effect profile of pregabalin is more linear, allowing the patient to tolerate a higher dose. The less frequent dosing of pregabalin may also be preferred.

Combination treatment

Often patients will benefit from a combination of two different drug classes used together (e.g., an SNRI with a tricyclic antidepressant, or an SNRI with a gabapentinoid), whereas other patients may respond to only one class of drug.[149][150][151][173] However, in practice, combining all three drug classes is rare.

SNRIs and tricyclic antidepressants may be used together (e.g., the SNRI given in the morning with the tricyclic antidepressant given at night); however, there is a risk of serotonin syndrome (considered rare in clinical practice) associated with using these two drug classes together.

Analgesics

There is no evidence that non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are effective in fibromyalgia, which supports the understanding of the underlying mechanisms of fibromyalgia.[174][175]

Despite the evidence and recommendations against their use, NSAIDs and opioids use in fibromyalgia is widespread.[122]

However, an NSAID may be beneficial in the setting of fibromyalgia with a comorbid condition such as osteoarthritis, where there is ongoing peripheral nociceptive input.

Tramadol, a weak opioid, is recommended as a potential treatment for fibromyalgia.[122] Even though tramadol has demonstrated a positive effect for pain in fibromyalgia when combined with an antidepressant or analgesic, no difference was found for tramadol alone compared with placebo.[176] It should also be noted that the adverse effect profile and long-term misuse potential associated with tramadol treatment are much higher than other pharmacological treatments for fibromyalgia.

There is no evidence that stronger opioids are effective, and they should not be prescribed for long-term use in fibromyalgia. Concern that these patients may be at increased risk of opioid-induced hyperalgesia may be largely anecdotal.

Patients refractory to initial treatment

Some patients, especially those with severe symptoms (i.e., high FIQR score, e.g., 70+) including long-standing symptoms and functional consequences (e.g., disability, compensation), those on high-dose opioids, those with significant psychiatric comorbidities, patients who do not respond to initial treatment, and those who have had multiple 'failed' surgical procedures, will not respond to this approach and will need interdisciplinary care.

Referral

Referral to an appropriate specialist should be individualised depending on the patients symptoms, for example:

Physical therapy: if the general physical activity recommendations are unsuccessful
Occupational therapy: if the patient has significant fatigue, vocational impairment
Psychology: for cognitive behavioural therapy
Psychology/psychiatry: if the patient has moderate to severe depressive symptoms
Rheumatology: if the diagnosis of rheumatological disease is in question
Neurology: if diagnosis of neurological disease is in question
Sleep medicine: if a primary sleep disorder is suspected.

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