Fibromyalgia Treatment

• Mild fibromyalgia can be managed in primary care while those who were not responsive to initial treatment or have significant comorbidities should be referred to a rheumatologist

Goals of Treatment

• To reduce symptoms
• To improve the physical and mental health of patients as well as their quality of life
• To reduce the need for medicine
• To enhance independence

General Principles

• Treatment should be individualized based on the severity of pain, presence of other symptoms or comorbidities and the degree of functional impairment
• Use a multidisciplinary approach and offer individually-tailored strategies that include both pharmacological and non-pharmacological therapies in the management of fibromyalgia
• Medications should be started at very low doses and gradually increased to reach the final dose that is set by the patient, based on efficacy and side effects
• Patients should be encouraged to identify specific goals regarding health status also with quality of life at the initiation of treatment, with re-evaluation of goals during the follow-up
• Patients with poor response to standard regimens are advised to include physical activity and psychotherapy in their management

Combination Therapy

• Patients with fibromyalgia experience multiple symptoms that may benefit from several different drugs that have different mechanisms of action and may preferentially benefit 1 symptom domain over another
• Recommended for patients who are unresponsive to monotherapy
• Selection of agents is based on patient's tolerance, drug availability, present comorbidities and cost
• Combination therapy should involve drugs with different mechanisms of action
• To ensure safe combination, it is important to know the potential drug-drug interactions
• Combination therapy is best introduced sequentially so that patient can gain a sense of effectiveness of 1 drug and adjust to adverse effects that may be more prominent initially and then diminish or resolve before introducing a second drug

Outcome Measures

• A comprehensive assessment of symptom severity (eg pain, fatigue, sleep quality, anxiety, depression), physical function, and psychosocial status is the key status and outcome variables in fibromyalgia
• Eg visual analog scales (VAS) for pain, fibromyalgia impact questionnaire (FIQ) that measures physical function, work status, depression, anxiety, pain, fatigue and well being during the preceding week

Tricyclic Antidepressants (TCAs)

• Considered as initial therapy in patients with fibromyalgia
• Have the strongest evidence for medication efficacy in the treatment of fibromyalgia, particularly Amitriptyline
• Recommended as nighttime medication
• Use is limited by a lack of uniform effectiveness and relatively high frequency of side effects
  • Efficacy of the drugs may decrease over time in some patients

• Has a strong evidence for medication efficacy in the treatment of fibromyalgia
• Blocks neuronal reuptake of noradrenaline and serotonin thus increasing synaptic concentration of serotonin and/or norepinephrine in the central nervous system
• Indirect comparison in meta-analyses demonstrated greater efficacy of Amitriptyline in the treatment of fibromyalgia than for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs)

• An analog of the neurotransmitter gamma aminobutyric acid; it binds to the alpha₂-delta subunit resulting in modulation of Ca channels and reduction in the release of several neurotransmitters, including glutamate, norepinephrine, serotonin, dopamine and substance P
• Recommended to be started with the lowest possible dose

Gabapentin

• Clinically effective in the treatment of fibromyalgia
• Alternative to Pregabalin
• Studies show great reductions in level and response to pain, sleep improvement, and overall impact of fibromyalgia after treatment

Pregabalin

• Approved for the treatment of patients with fibromyalgia
• Considered an alternative in patients who are not responsive or intolerant to Amitriptyline and patients with more sleeping problems
• Based on meta-analysis, Pregabalin was found to be superior than placebo and Milnacipran in providing pain relief
• Provides significant improvements in sleep quality, fatigue and health-related quality of life

Cyclobenzaprine

• Has a strong evidence for medication efficacy in the treatment of fibromyalgia
• Alternative medication to Amitriptyline
• Officially classified as a centrally-acting skeletal muscle relaxant but shares similar structural properties with tricyclic antidepressants (TCAs)
  
  • It acts on the brain stem, decreasing the tonic-somatic motor activities

• Relaxes tense muscles leading to pain relief and facilitates sleep

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

• May be used as adjuncts for analgesia when combined with TCAs
• There is no evidence of their effectiveness when used alone in the treatment of fibromyalgia

Opioids

• Strong opioids are generally not recommended
• Should only be considered for moderate to severe pain unresponsive to conventional treatment and only after all other pharmacological and non-pharmacological therapies have been exhausted

Pramipexole

• It is a nonergot-derivative dopamine receptor agonist
• Pramipexole provides greater improvement in the mean pain score after 14 weeks of study; however, higher doses were used than many patients can tolerate
  
  • Hence, further study is needed to evaluate the efficacy and safety of Pramipexole
  • Its use may be limited in patients refractory to multiple approved or better established medications

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• These agents have greater neuroreceptor selectivity; considered more potent and are better tolerated than older TCAs

Duloxetine

• Approved for the treatment of fibromyalgia in several countries
• Highly selective inhibitor of serotonin (5-HT) reuptake
• Significantly reduces pain severity and improves global assessments
  
  • Majority of its impact on pain was a direct effect

• Also improves mental fatigue but not general fatigue
• Based on meta-analysis, Duloxetine was found to be superior than placebo and  Milnacipran in providing pain relief
• Based on a pivotal study, it was shown that Duloxetine neither helped nor hindered sleep quality
• Best tolerated in the morning

Milnacipran

• Approved for the treatment of fibromyalgia in some countries
• Has mild N-methyl-D-aspartate inhibitor properties
• Reduces pain and improves global status and physical function in patients with fibromyalgia
• May be used as an initial therapy in patients who have exhaustion
• Alternative to Duloxetine in patients with severe fatigue in addition to pain
• Similar to Duloxetine, Milnacipran does not interfere with sleep nor does it help with sleep

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Considered to have less impact in alleviating pain of fibromyalgia than TCAs or the newer SNRIs, although they may be helpful for clinical domains like fatigue or mood disorder

Fluoxetine

• There is moderate evidence of the efficacy in the treatment of fibromyalgia
• Based on a flexible placebo-controlled dose study, Fluoxetine demonstrated improvement on FIQ score as well as subscores for pain, fatigue and depression

Tramadol

• Inhibits reuptake of norepinephrine and serotonin, and enhances serotonin release
  
  • Alters perception and response to pain by binding to mu-opiate receptors in the central nervous system

• Provides effective pain relief either alone or in combination with Paracetamol
• Based on a large randomized controlled trial, VAS for pain was decreased, pain relief was improved and pain threshold was reduced after treatment with Tramadol
• Should be used with caution due to possibility of typical opiate withdrawal symptoms after discontinuation and the risk of abuse and dependence

Tropisetron

• A potent selective and competitive antagonist of 5HT₃ receptors
• Reduces pain and improves function in fibromyalgia
• Has analgesic effect based on small trials of fibromyalgia patients in a bell-shaped curve dose effect

Combination Therapies

SNRI plus Anticonvulsant

• Significant pain reduction and global improvement with the addition of Milnacipran in patients with suboptimal response to Pregabalin
• Combination of Duloxetine and Pregabalin demonstrated significant improvement in clinical outcomes including pain, sleep and function compared to monotherapy

SSRI plus TCA

• Combination of Fluoxetine and Amitriptyline was noted to have better outcome measures compared to either drug alone
  
  • Same results were noted in the combination of Fluoxetine and Cyclobenzaprine over a 12-week period

Other Agents

• Corticosteroids are useful only as management for coexisting inflammatory processes
• Cannabinoids (eg Nabilone, Dronabinol) may be considered for fibromyalgia patients who are greatly affected by lack or disturbance of sleep

• Involves a systematic and strategic approach
• An individualized treatment program is recommended

• Recommended as the first intervention among the treatment strategies for fibromyalgia patients
• Goal is to make a gradual move toward functional independence and fitness
• All modes of exercise can be modified based on the severity of fibromyalgia and presence of comorbidities
• Aerobic type is usually recommended versus resistance and flexibility type
• Involves changing the patient's mindset and a need to adopt for a slower paced life
  • Stress the importance of pacing, to limit exacerbations which triggers patient's discontinuation to program
  • Advice for interventions of single exercise (aerobic training, strength training, flexibility training) or >1 type of exercise
• Based on systematic review of controlled trials, low impact aerobic exercise was found to have beneficial effects on aerobic performance, pain and pressure thresholds over tender point sites in those subjects who received aerobic exercise training
• Studies have shown that aerobic exercise in warm pools seems to be as beneficial as land-based aerobic exercise, with additional benefits in mood and sleep duration
• The type and intensity of exercise program should be individualized
  • Optimal cardiovascular fitness training requires a minimum of 30 minutes of aerobic exercise 2-3x/week
• There is an increasing evidence for the beneficial effects of strength training
  • Strength training 2x/week is encouraged
• Advise patients to avoid pain by stretching to the point of resistance, not to the point of pain
  • Recommended especially for patients with joint hypermobility
• Effective exercise can be done individually or in a group
  • Type of exercise is largely determined by patient preference and access to group classes and warm-water pools; pool exercise classes should not be confused with swimming

• Based on recent reviews on flexibility training (eg yoga, pilates, T’ai Chi), the results showed improvement in pain, function and quality of life but adherence to the program is recommended
• Qigong and T’ai Chi offer some promise of efficacy but more rigorous assessment is needed for these to be considered an evidence-based treatment for fibromyalgia
• Acupuncture could be a complementary treatment, but needs further studies due to conflicting evidence of efficacy for fibromyalgia 
• Slow-paced/relaxing, self-chosen, familiar and highly pleasant music may help provide analgesia and improve functional mobility
• Hydrotherapy may be of benefit for the treatment of pain, health status, and tender point counts and mitigates symptoms as well to improve function
• Manual therapy (eg massage therapy and joint manipulation) has been shown to be beneficial

Psychological and Behavioral Therapies

• Course of treatment will usually last for 5-20 sessions, with each session lasting >30-60 minutes
• There is good evidence to support the beneficial effect of psychological therapies, particularly cognitive behavioral therapy (CBT)
  • Suggested as an adjunct to drug therapy
  • CBT is the combination of cognitive therapy to modify maladaptive thoughts and behavioral therapy to increase adaptive behavior
  • The goal of CBT is to increase self-management, which includes moving patients toward more adaptive beliefs regarding their ability to control fibromyalgia symptoms, resulting in increased functioning
• Based on a meta-analysis, a number of psychological measures provided a statistically significant, but small to medium effect on short- and long-term pain reduction in patients with fibromyalgia
  
  • All psychological methods were comparably effective in decreasing depression and pain severity
  • It was concluded that patients with fibromyalgia should be treated with combination methods that include psychological interventions as a major component, such as high-dose CBT with relaxation/biofeedback

• Other methods that may be helpful include educational interventions, relaxation training, activity pacing, guided imagery, written emotional disclosure, distraction strategies

Physical Therapy and Modalities

• Diffuse and regional pain is improved by strategies like sauna, hot baths and showers, hot mud, and massage; however, excessive dependence on these physical modalities may confound patient’s efforts to attain self-efficacy for pain control
• Trigger-point injection, chiropractic manipulation and myofascial release may be well accepted by patients but these modalities have questionable efficacy

Transcranial Direct Current Stimulation

• Makes use of weak direct current for 20 minutes into the brain via electrodes placed on the cranium in order to modify brain activity
• Daily use improves pain and physical function in patients with fibromyalgia
• Direct stimulation to the primary motor cortex was associated with reduced arousals, improved sleep efficiency, and improvement of symptoms of fibromyalgia

Repetitive Transcranial Magnetic Stimulation

• Applies magnetic waves to the cranium
• Daily use for 30 minutes improves sleep efficiency, reduced arousals and improvement in symptoms
• Meta-analysis demonstrated benefit for fibromyalgia but further studies are needed to confirm it's effectiveness

Other Therapies

• There has been mixed or limited evidence for efficacy of hypnotherapy, mineral springs or salt baths (balneotherapy)