New frontiers in fibromyalgia care: A review of current and emerging treatments

Milnacipran and pregabalin are among the pharmacological agents newly available for treating fibromyalgia, alongside non-pharmacological approaches like mindfulness-based stress reduction and aquatic exercise. These developments expand the range of options for improving fibromyalgia care and alleviating symptoms.

Fibromyalgia is a chronic pain disorder mainly affecting women. This debilitating ailment is characterized by widespread pain, tenderness, and fatigue. Even with comprehensive research, its cause remains unclear, and there is no known cure. Its deep impact on daily living highlights the pressing need for effective therapies. Recent advancements offer novel avenues for addressing fibromyalgia.

While pharmacological treatments like antidepressants and muscle relaxants can yield relief, their side effects have led to the development of non-pharmacological approaches. Techniques like cognitive-behavioral therapy (CBT), exercise, acupuncture, and massage therapy have demonstrated promise in mitigating pain and fatigue. Additionally, lifestyle changes like better sleep hygiene and stress management are also fundamental for symptom management.

For fibromyalgia cure, recent advances encompass new pharmacological agents like milnacipran and pregabalin, as well as non-pharmacological approaches like aquatic exercise and mindfulness-based stress reduction (MBSR). These methods have illustrated promising results in attenuating clinical signs and promoting a better quality of life. Healthcare professionals must stay updated on these developments to offer comprehensive, evidence-based care and effectively tackle the complex symptoms of fibromyalgia.

RATIONALE BEHIND RESEARCH

Fibromyalgia is a multifaceted chronic pain syndrome  that greatly affects the quality of life. Its elusive etiology highlights the necessity for efficient therapeutic strategies. Hence, this study was conducted.

OBJECTIVE

The aim was to summarize current therapeutic options for fibromyalgia, highlight recent updates, and evaluate the evidence supporting these advancements. It also aimed to enhance medical care professionals' knowledge and support informed decision-making to yield optimal care.

Literature search

Relevant papers issued between 2000 and 2023 were found by searching databases, including Embase, PubMed, Web of Science, Scopus, and MEDLINE. The following search terms were integrated with Boolean operators: advancements, alternative, complementary, developments, fibromyalgia, innovative, intervention, latest, novel, non-pharmacological, pharmacological, therapy, treatment.

Inclusion criteria

• PICOSTL (population, intervention, comparison, outcomes, study design, timeframe, and language) criteria was tracked, as depicted below:
• Population: Adult individuals (≥ 18 years) suffering from fibromyalgia syndrome (FMS).
• Intervention: Pharmacological and non-pharmacological management strategies for FMS, encompassing dose, frequency, duration, and method of administration.
• Comparison: Research that included a clearly delineated control group, if relevant.
• Outcomes: (a) Primary or secondary endpoints suitable for FMS cure—like quality of life, physical function, pain, or other symptoms connected to FMS, (b) Adverse effects linked with the interventions used.
• Study design: Observational studies, Systematic reviews, Randomized controlled trials.
• Timeframe: Studies issued between 2000 and 2023.
• Language: Studies issued in English.

Exclusion criteria

• Studies with small sample sizes.
• Study designs like case series and case reports.
• Studies devoid of a clear description of the interventions used.
• Studies lacking information on statistical significance or effect sizes.
• Studies that had inadequately defined interventions.
• Studies with unreported key outcomes or undesired events.

Study selection and data extraction

With the assistance of a structured data extraction tool, two reviewers separately retrieved data from the eligible manuscripts. Information on participant characteristics, intervention type, research design, outcome measures, and findings were all incorporated in the data extraction form.

Data and statistical analysis

N/A

Risk of bias and quality assessment

Two separate reviewers scrutinized the integrity of the included research employing suitable tools (for instance, the Joanna Briggs Institute critical appraisal tool and the Cochrane risk of bias tool). In case of discrepancies, a third opinion was requested. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and adhered to referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

The review process was rendered reproducible, transparent, and of high quality. This approach significantly bolstered the review's credibility and validity.

Study outcomes

(a) Primary or secondary outcome measures linked to FMS cure, such as quality of life, physical function, pain, or other FMS-linked symptoms.

(b) Adverse events related to the interventions used.

Outcomes

Study and participant characteristics:

N/A

Study quality:

N/A

Effect of intervention on the outcome:

[1] Current Treatment Strategies for Fibromyalgia: An Overview

• Pharmacological treatments for fibromyalgia include opioids, muscle relaxants, anticonvulsants, analgesics, and antidepressants.
• Analgesics yield short-term relief but aren't ideal for extended duration because of potential deleterious effects. Antidepressants (serotonin reuptake inhibitors [SSRIs], selective serotonin-norepinephrine reuptake inhibitors [SNRIs], and tricyclic antidepressants [TCAs]) help monitor pain-related neurotransmitters. On the other hand, anticonvulsants (gabapentin, pregabalin) diminish nerve activity implicated in pain signaling.
• Muscle relaxants like cyclobenzaprine and tizanidine decrease spasms and encourage relaxation.
• For addressing severe pain, opioids may be used. However, they are discouraged for long-term usage owing to risks of addiction and exacerbation of symptoms.
• Non-pharmacological therapies for fibromyalgia encompass CBT, exercise, sleep care, occupational therapy, hydrotherapy,  transcutaneous electrical nerve stimulation  (TENS), gradual physical activity therapy, psychological therapies, and complementary approaches like nutritional supplements, acupuncture, mind-body therapies, and massage.
• A personalized treatment plan must be developed with healthcare providers on the basis of individual needs.

[2] Advances in Fibromyalgia Treatment: Latest Insights

[a] Pharmacological treatments

1. SNRIs

(a) Milnacipran

• FDA-approved drug for fibromyalgia treatment.
• Effectively addresses multiple symptoms like pain, fatigue, and sleep disturbances.
• Clinical trial unveiled a remarkable attenuation in pain scores than placebo.
• Enhances quality of life and function with a good safety and tolerability record.
• Clauw et al.'s study: Both 100 and 200 mg per day doses of Milnacipran markedly improved pain and other accompanying manifestations.
• Common adverse effects: Nausea and headache (rarely reported).

(b) Duloxetine

• FDA-authorized drug that has demonstrated effectiveness in abating pain, fatigue, and depression.
• Clinical trial presented substantial pain mitigation as opposed to placebo.
• Doses of 60, 90, and 120 mg per day improved fatigue, functioning, mood, pain
• sleep, stiffness, well-being.
• Safe and well-tolerated treatment that boosts function and quality of life of fibromyalgia-affected patients.

2. Anticonvulsants

(a) Pregabalin

• FDA-certified drug that diminishes anxiety, pain, and sleep irregularities.
• Clinical trial illustrated pivotal pain alleviation in comparison with placebo.
• Efficient at 450 mg/day, improving sleep and reducing fatigue.
• Common side effects: Dizziness and somnolence, dose-dependent.
• Boosts patients' functional outcomes and overall well-being.

(b) Mirogabalin

• A novel gabapentinoid for fibromyalgia cure.
• A 2019 study depicted effectiveness in minimizing pain and enhancing sleep quality.
• Common CNS side effects: Somnolence, headache, and dizziness, with dose-dependent incidence.
• Other side effects: Edema, fatigue, constipation, diarrhea, weight gain, and nausea.

(c) Lacosamide

• Exhibited pain-reducing properties in animal research.
• 2012 randomized trial: Lacosamide proved more beneficial than placebo in attenuating pain and improving sleep in fibromyalgia patients.
• Common adverse effects: Tremor, dizziness, vertigo, ataxia, vomiting, balance issues, fatigue, diplopia, and nausea.
• Adverse effects are dose-dependent.
• Further studies are warranted to confirm its potential for fibromyalgia relief.

3. Cannabinoids

• For fibromyalgia care, cannabidiol (CBD) and tetrahydrocannabinol (THC) are being explored as viable options. This is because they engage with the endocannabinoid system, which influences pain, mood, and sleep.
• Habib et al.'s study: THC/CBD spray markedly reduced pain and boosted the quality of sleep.
• Sagy et al.'s study: CBD-rich cannabis extract mitigated pain, anxiety, and low mood in fibromyalgia patients.
• Potential side effects encompass dry mouth, dizziness, and cognitive deficits, requiring close medical monitoring.
• May offer a cost-effective, well-tolerated option, but more research is needed on long-term safety and effectiveness.
• Legal status of cannabinoids varies by jurisdiction; consultation with a clinical practitioner is advised.

4. Tropisetron

• 5-hydroxytryptamine (5-HT3) receptor antagonist.
• Stratz et al. study: Tropisetron proved more efficient as opposed to placebo in alleviating pain, tiredness, and enhancing sleep quality.
• Arnold LM study: Daily 2 mg dose of tropisetron for five days offered pain relief lasting up to two months.

5. Sodium oxybate

• Central nervous system (CNS) depressant.
• Spaeth et al. Study: Sodium oxybate effectively lessened pain, fatigue, and sleep disorders.
• Common adverse effects:  Anxiety, vomiting, nausea, and dizziness.
• Additional long-term analyses are required to examine efficiency and safety.

[b] Non-pharmacological treatments

1. Mind-body interventions

• Mind-body interventions like MBSR aid to improve fibromyalgia symptoms by addressing stress, psychological distress, and nervousness.
• 2022 study: MBSR mitigated pain and fatigue, and boosted quality of life in fibromyalgia sufferers.
• 2012 study: CBT lowered pain, anxiety, emotional distress, and enhanced physical function.
• Further examination is needed to scrutinize the long-term sustainability of these remedies.

2. Exercise therapy

• Exercise therapy, including aerobic and resistance training, leads to improvement in fibromyalgia symptoms by mitigating pain, fatigue, and enhancing physical function.
• 2022 study: Combined aerobic and resistance training lessened pain, fatigue, and improved quality of life.
• Exercise helps ease pain, sleep, and total well-being.
• Low-impact aerobic exercises (walking, swimming, cycling) and strength/stretching exercises benefit muscle strength and flexibility.

3. Acupuncture

• Few studies have documented the utility of acupuncture (insertion of thin needles into specific body points) for pain and quality of life improvement in fibromyalgia patients.
• More assessment is warranted to figure out the most useful acupuncture points and duration of treatment for fibromyalgia cure.

4. TENS

• A non-invasive strategy that employs electrical impulses to control pain signals in nerves.
• In 2015, Noehren et al. conducted a study on the impact of TENS on fibromyalgia patients, finding it to potently improve pain, fatigue, and physical function.

5. Low-level laser therapy (LLLT)

• Employs low-level laser light to decrease inflammation and regulate cellular activity.
• de Carvalho et al. found LLLT valuable in ameliorating pain and lethargy, and boosting life quality in fibromyalgia sufferers.

6. Hydrotherapy

• Uses water for therapeutic purposes, including warm water immersion and aquatic exercise.
• 2006 study: Hydrotherapy successfully reduced pain and fatigue, and improved physical function in fibromyalgia cases.

7. Yoga therapy

• Includes meditation practices, body positions, and respiratory exercises to enhance physical and mental health.
• 2010 study: Yoga therapy effectively alleviated pain, anxiety, and depression, and improved physical function in individuals with fibromyalgia.

8. Music therapy

• Uses music for relaxation and pain management.
• Some studies found it useful in abating discomfort, anxious feelings, and depressive states in those suffering from fibromyalgia.
• More exploration is required to completely comprehend its benefits.

9. Mindfulness-based art therapy

• Combines art-making with mindfulness practices to enhance physical and mental health.
• 2014 study: MBAT effectively reduced discomfort, nervousness, and depressive conditions, and improved life quality in fibromyalgia patients.

10. Tai chi

• Chinese martial art that blends slow and precise movements with meditative practices.
• Wang et al. found that tai chi effectively reduces pain, fatigue, and improves physical function in fibromyalgia cases.

11. Virtual reality distraction therapy

• Uses virtual reality technology to distract from pain and provide relaxation.
• Beneficial for reducing pain, fatigue, anxiety, and depression in fibromyalgia cases.
• Facilitates dynamic balance, aerobic capacity, and quality of life.

12. CBT

• Talk therapy that concentrates on altering unhealthy thoughts and actions for mental well-being.
• Teaches resilience techniques, calming practices, and aids to acknowledge and refute unproductive thoughts.
• Prados et al. found CBT efficient in diminishing worry, pain, emotional instability, and improving well-being in fibromyalgia patients.

13. MBSR

• Combines yoga practice and mindfulness meditation to curtail stress and ameliorate mental and physical health.
• Perez-Aranda et al. found that MBSR effectively lessens pain and fatigue in fibromyalgia-affected people, thereby improving their quality of life.

14. Graded exercise therapy

• A structured exercise program that progressively escalates the degree of physical activity to improve physical function and pain in fibromyalgia-affected individuals.
• Although useful for alleviating symptoms and quality of life, it may cause increased pain in some patients.

15. Occupational therapy

• Helps manage fibromyalgia symptoms and maintain daily activities.
• Therapists assist with energy conservation, improving environments, and adapting activities to combat pain and fatigue.

16. Massage therapy

• Valuable in curtailing pain, stiffness, and fatigue by manipulating soft tissues.

17. Dietary supplements

• Creatine, magnesium, and soy supplements have been studied for their possible advantages in tackling fibromyalgia-related signs.

Fibromyalgia affects millions globally with a complex mix of genetic, environmental, and psychological causes. Diagnosis of this chronic pain ailment is guided by symptoms and the elimination of other conditions. Though it impacts quality of life, a multidisciplinary approach helps manage the condition effectively, allowing patients to lead fulfilling lives. Staying current on treatment strategies is key to optimal care.

This review used clear inclusion criteria and an extensive search strategy to ascertain relevance and thoroughness. It offered valuable clinical insights on the effectiveness and safety of fibromyalgia therapies, with transparency enhanced by detailed methods and adherence to PRISMA guidelines. Studies were critically appraised utilizing the Cochrane tool and GRADE approach, improving reliability, while the inclusion of diverse populations increased generalizability. Registration with PROSPERO further strengthened the review's rigor.  For fibromyalgia management, medications like duloxetine, pregabalin, and milnacipran should be considered for pain alleviation.

Include exercise therapy, like aerobic and resistance training, in the intervention plan. CBT can aid to reduce pain, boost life quality, and relieve mood disorders. Mind-body holistic therapies like tai chi and yoga practices can also relieve pain and boost physical function. Educate patients about fibromyalgia for better outcomes and use a multi-modal, personalized therapeutic approach. Involving patients in decision-making and ensuring early intervention with regular symptom monitoring is fundamental for optimal results. Future research could explore:

• Tianeptine as a potential fibromyalgia cure due to its analgesic effects in animal models.
• Pramipexole, a dopamine agonist, for its influence on sleep, fatigue, and pain in fibromyalgia.
• Agomelatine, a melatonin receptor agonist and serotonin antagonist, for its potential to improve sleep wellness and reduce symptoms like fatigue and pain.
• Sleep improvement strategies like cognitive behavioral therapy for insomnia (CBT-I) and education to assess their efficiency in larger, diverse populations.
• Biofeedback therapy to determine the best treatment parameters and patient characteristics for effectiveness.
• Balneotherapy (a form of hydrotherapy) to explore its influence and ideal therapeutic approach.
• Transcranial magnetic stimulation to find the best parameters (frequency, intensity, and duration of treatment) and understand its mechanisms for ameliorating pain and function.