Treatment of fibromyalgia

                               Dr. KS Dhillon

Introduction 

Fibromyalgia is a common, debilitating, and often overlooked, clinical syndrome. It affects about 2% of the population with a peak incidence in middle-aged women (90.6%) [1]. Fibromyalgia overlaps with other functional somatic disorders, such as chronic fatigue syndrome, irritable bowel syndrome, and temporomandibular joint dysfunction [2]. Fibromyalgia commonly co-occurs with anxiety and mood disorders. Research shows that, although functional somatic disorders are related and potentially interact with psychological conditions, they are usually independent [3]. Fibromyalgia is characterised by features of widespread somatic pain and deep tissue tenderness. This results from sensitisation of neural pain pathways [4]. 

The patients can also have a variable combination of sleep disturbance, fatigue, cognitive dysfunction as well as psychological distress. These symptoms can be present despite the absence of objective abnormalities on clinical examination.

There is an incomplete understanding of this syndrome's pathogenesis. There is increasing evidence for a mechanism-based management approach to this syndrome [5,6]. These are likely to be more effective if introduced early, and this makes it important to make an early timely diagnosis. 

Pathophysiology

Fibromyalgia usually develops spontaneously [7]. It is likely to represent a maladaptive, stereotypical, biological response of the body to the cumulative effects of physical or psychological stress in people who are genetically predisposed to it [8]. It is also associated with psychiatric and musculoskeletal disorders, and that leads to poorer outcomes [9,10]. It can also occur after an infection.

The prevalence of fibromyalgia is increased in people with chronic medical disorders [11]. Fibromyalgia is primarily derived from pathophysiology within the central nervous system, where there is disordered sensory processing. There is growing evidence to suggest that fibromyalgia may comprise multiple pathogenetic subsets, including originating partly within the peripheral nervous system [4,12,13]. With time, most cases of fibromyalgia evolve out of persistent regional pain [14].

Diagnosis

The fibromyalgia diagnostic criteria [15] have evolved from the recognition that fibromyalgia is a spectrum disorder, both with regards to spatial distribution of symptoms and pain severity. Diagnosing fibromyalgia can be challenging.

The condition should be considered as a possibility in all patients with persistent musculoskeletal pain, fatigue, or sleep disturbance, especially when such symptoms are out of proportion to the severity of any background chronic illness [16]. 

A practical, validated, self-assessment tool based on the diagnostic criteria has been developed [17] to quantitate the symptoms of fibromyalgia [18,19] (Table 1).

Scores above certain thresholds [19] yield reasonable sensitivity and specificity compared to the original classification criteria [20]. Other disorders that fully explain the patient's symptoms have to be excluded [21]. Examination for deep tissue tenderness, which was required by the old criteria, is now not needed. Investigations are needed to exclude treatable comorbidities and potential differential diagnoses, such as thyroid dysfunction [22].

                 Fibromyalgia survey questionnaire

I. Using the following scale, indicate for each item the level of severity over the past week by checking the appropriate box.

0: No problem

1: Slight or mild problems; generally mild or intermittent

2: Moderate; considerable problems; often present and/or at a moderate level

3: Severe; continuous, life-disturbing problems

Fatigue [ ] 0 [ ] 1 [ ] 2 [ ] 3

Trouble thinking or remembering [ ] 0 [ ] 1 [ ] 2 [ ] 3

Waking up tired (unrefreshed) [ ] 0 [ ] 1 [ ] 2 [ ] 3

II. During the past 6 months have you had any of the following symptoms?

Pain or cramps in the lower abdomen [ ] Yes [ ] No

Depression [ ] Yes [ ] No

Headache [ ] Yes [ ] No

III. Joint/body pain

Please indicate below if you have had pain or tenderness over the past 7 days in each of the areas listed below.

Please make an X in the box if you have had pain or tenderness. Be sure to mark both the right side and left side separately.

[] Shoulder, left [ ] Upper leg, left [ ] Lower back

[ ] Shoulder, right [ ] Upper leg, right [ ] Upper back

[ ] Hip, left [ ] Lower leg, left [ ] Neck

[ ] Hip, right [ ] Lower leg, right

[ ] Upper arm, left [ ] Jaw, left [ ] No pain in any of these areas

[ ] Upper arm, right [ ] Jaw, right

[ ] Lower arm, left [ ] Chest

[ ] Lower arm, right [ ] Abdomen

IV. Overall, were the symptoms listed in I–III above generally present for at least 3 months? [ ] Yes [ ] No

Table 1

Management

Spontaneous recovery usually does not occur. The main aim of treatment is to improve symptoms, function, and quality of life [23]. The treatment is individually tailored. It is multimodal, multidisciplinary, and combines both pharmacological and non-pharmacological approaches [5].

 

Non-pharmacological approach

The medical treatment of fibromyalgia is usually only partially successful [5], hence health professionals need to give their patients sustained support to become active self-managers. This is the most important intervention to enable the patient to live successfully with this debilitating multidimensional disorder.  Self-management skill training is best delivered within a small group setting where education, training, coping skills, and cognitive behavioural approaches are explored [24]. Thereafter, skills can be consolidated by trained peer mentors [25]. For health professionals, an open and patient-centered communication style is recommended [26].

Among non-pharmacological therapies, exercise and psychoeducational approaches have the greatest evidence of efficacy [5]. Biomechanical assessment and subsequent exercise monitoring by a physical therapist is desirable. A referral to a psychologist should be considered in all patients, especially in those who are more psychologically distressed.

Pharmacological approach

Drug therapy has a supportive role in the management of symptoms. Some patients do not tolerate and others do not benefit from drugs. All drugs are started at low doses and gradually the dose is increased. The drugs are used to manage the patient's predominant symptoms such as pain, sleep disturbance, and psychological distress. The drugs are stopped if they provide no benefit.

Antidepressants

Traditionally low-dose amitriptyline has been the first-line drug for treating pain and sleep disturbance in patients with fibromyalgia. The evidence supporting the use of amitriptyline is of low quality. 

A Cochrane Database Systematic  Review by Moore et al [27] showed that there was no first‐tier evidence on the efficacy of amitriptyline in fibromyalgia. There was some second-tier evidence that amitriptyline at 25 or 50 mg daily was better than placebo. About 64% of participants taking amitriptyline had adverse effects. Only about 38% of participants benefited from the use of amitriptyline. About 5% withdrew because of lack of efficacy with amitriptyline. Tolerance development and weight gain limit the use of amitriptyline. 

Serotonin and noradrenaline (norepinephrine) are mediators of descending inhibition in the nervous system. Their concentrations are reduced in patients with fibromyalgia. Hence, it is justified to have a trial of a serotonin noradrenaline reuptake inhibitor. In trials conducted by the manufacturers, there is low-quality evidence that Duloxetine at 60 mg per day is effective in the treatment of fibromyalgia [28].

Milnacipran as well inhibits the reuptake of serotonin and noradrenaline (norepinephrine). It can be used to treat fibromyalgia. The recommended dose is 100 mg daily in divided doses. There is some high-quality evidence which shows that it has modest efficacy [29].

Antiepileptic drugs

In patients with fibromyalgia, the concentrations of the pain facilitatory neurotransmitters glutamate and substance P in the central nervous system are elevated. These transmitters are the targets of gabapentin and pregabalin which have potential pain modulatory, sleep-promoting, and anxiolytic actions. 

A Cochrane Database Systematic  Review by Nurcan Üçeyler et al [30] showed that anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems in patients with fibromyalgia. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide, and levetiracetam in patients with fibromyalgia. 

Other drugs

There is weak evidence that NSAIDs are ineffective in the treatment of patients with fibromyalgia [5]. There is no trial evidence of efficacy for paracetamol used alone. There is preliminary evidence from randomized controlled trials of the efficacy of tramadol [31], pramipexole [32], and memantine [33]. Pure mu-opioid receptor agonists, such as codeine, oxycodone, and fentanyl are contraindicated because of poor clinical response and increased risk of opioid-induced hyperalgesia [31].  

Conclusion

Fibromyalgia can produce profound, multidimensional disability, and multidisciplinary management is required. A systematic, patient-centered approach can produce meaningful improvements in patient's symptoms, function as well as quality of life. Non-pharmacological treatments have an important role to play. Some drugs can complement an active rehabilitation program. There is some evidence for the use of amitriptyline, pregabalin, duloxetine, and milnacipran for the treatment of fibromyalgia. However, not all patients will benefit from these drugs. Patients should be monitored for adverse events resulting from the use of these drugs.

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