Fibromyalgia is a multifactorial chronic pain syndrome that can be bewildering and frustrating; it is rewarding for both patients and physicians to manage it well. Fibromyalgia affects approximately 2% to 4% of the population. While older research suggested the ratio of women to men affected is about 7 to 1, it is likely much lower due to evolving diagnostic criteria.1 This article aims to briefly review the evidence for nonpharmacologic and pharmacologic management of this condition.
Methods
This article brings together the evidence from a series of Tools for Practice articles. Tools for Practice articles answer a specific clinical question by searching PubMed and the Cochrane Database of Systematic Reviews, focusing on systematic reviews (SRs) of randomized controlled trials (RCTs). RCTs are searched in addition to SRs for 2 reasons: 1) if fewer than 2 SRs are found or 2) if the most recent SRs are more than 2 to 5 years old, more recent RCTs would be sought. When data are limited, a search of SRs of observational studies is considered. When available, meta-analyses of SRs are often prioritized, unless important methodologic issues exist. Data are extracted into a Microsoft Excel file and checked by a second reviewer. Response rates and responder analyses (eg, the proportion of people with 30% or greater improvement in pain) are preferred outcomes for ease of understanding the effects of the interventions.2 Tools for Practice articles are published after independent peer review.
Diagnosis of fibromyalgia
The diagnosis of fibromyalgia does not require specialist referral. The initial differential diagnosis is broad and a careful history and physical examination look for signs of inflammation, neurologic deficits, and hypermobility. Tender points are no longer used and the American College of Rheumatology uses the Widespread Pain Index (WPI) and Symptom Severity Score (SSS; both can be downloaded from the Royal College of Physicians: https://www.rcp.ac.uk/improving-care/resources/the-diagnosis-of-fibromyalgia-syndrome) to establish whether the clinical picture fits fibromyalgia.1 Initial blood testing includes complete blood count, thyrotropin level, C-reactive protein level, and celiac disease screening. Guided by history and physical examination findings, particularly if there is ambiguity in the clinical picture (ie, low scores on the WPI and SSS), other testing might include liver function; iron studies; magnesium, phosphate, and calcium levels; ferritin level; human immunodeficiency virus testing; or hepatitis screening. Antinuclear antibody testing is not recommended as a screening test.3
Approaches to management
Exercise. The Canadian fibromyalgia guideline states a cornerstone of treatment is to encourage patients to choose a graduated exercise program.4
SRs have evaluated aerobic, aquatic, resistance, and mixed exercise compared to usual care.5 RCTs report pain and fatigue scores, as well as overall function (most commonly with the Fibromyalgia Impact Questionnaire [FIQ]) on 0-to-100 scales, with higher scores related to worse symptoms. A minimally clinically important difference is considered about 10 to 15 points.6 RCTs did not report responder analyses.
Aerobic: Sessions were typically 2 to 3 per week with outcomes reported 6 to 24 weeks later.5 There were 3 SRs with 4 to 17 RCTs and 202 to 1095 patients. Compared to control participants, pain improved by about 11 points, fatigue improved about 6 points, and FIQ score improved about 8 points.
Aquatic: Sessions were 1 to 4 sessions per week for 4 to 32 weeks.5 There were 2 SRs of 6 to 16 RCTs including 271 to 881 patients. Compared to control participants, pain improved by 7 points, FIQ score improved by 5 points, and fatigue showed no difference.
Resistance: Sessions were about 2 per week for 8 to 21 weeks.5 There were 3 SRs with 9 to 11 RCTs including 443 to 839 patients. Compared to control participants, pain improved by 10 points, FIQ score improved by 19 points, and fatigue was uninterpretable based on reporting of standard mean differences rather than direct comparisons using the same scale.
Combined exercise: The exercise comprised a minimum 2 of aerobic, aquatic, resistance, or stretching sessions, with 2 to 3 sessions per week for 12 weeks.5 There were 2 SRs with 11 to 29 RCTs including 523 to 2088 patients. Compared to control participants, combined exercise improved pain by 6 points, fatigue by 13 points, and FIQ score by 7 points (Table 1).5
Exercise and symptom score improvements: Improvement is compared to control participants on a scale from 0 to 100.
The benefits of exercise in fibromyalgia remain unclear due to limited high-quality evidence. While improvements from baseline are seen, clinically meaningful changes versus control participants are rare, and responder analysis has not been assessed. Indirectly, improvements in mean pain scores (about 8%) are similar for some pharmacologic interventions, such as duloxetine.
However, exercise offers several ancillary benefits, such as reducing cardiovascular risk, osteoarthritis and back pain, and depression.5 While many patients avoid exercise for fear of exacerbating symptoms, evidence shows fibromyalgia symptoms may improve, rather than worsen, with exercise.
It is often difficult for patients with diffuse pain to begin and adhere to an activity program. Chronic pain and fibromyalgia clinics are rarely available so family physicians need to know other local and online resources. LivePlanBe+ (https://liveplanbeplus.ca), Gentle Movement @ Home (https://painbc.ca/find-help/gentle-movement-at-home), and Sleepwell (https://mysleepwell.ca) are examples of free websites that help people learn about chronic pain, exercise, sleep disorders, and self-management strategies. Physical activity prescriptions, combined with patient-specific goals and monitoring, may increase physical activity levels by up to about 1200 steps per day at about 1 year, with an additional 1 person becoming active for every 10 prescribed activity compared to general advice alone.7
Antidepressants
Duloxetine (60 to 120 mg daily): Four SRs with 6 to 7 RCTs and 2249 to 2642 patients after 8 to 27 weeks reported responder analyses compared to placebo.8 Duloxetine was shown to provide 30% or greater pain reduction in about 50% of patients versus 35% taking placebo (number needed to treat [NNT] of about 7). Effectiveness was similar between doses of 60 to 120 mg but no difference was seen between 30 mg and placebo. Common side effects included nausea in 26% of participants, constipation in 15%, and headache in 14% versus 4% to 8% with placebo; and hyperhidrosis (8%) versus 1% with placebo. Those taking the 120-mg dose were more likely to withdraw due to these adverse events, indicating that the 60-mg dose had the most favourable effect-to-side-effect ratio. The majority of the studies were industry funded.
Mirtazapine (15 to 45 mg daily): One SR of 3 RCTs and 591 patients after 7 to 14 weeks reported that 47% had a 30% or greater pain reduction versus 34% in the placebo group (NNT=8).8 The adverse effect profile indicated that somnolence was present in 41% versus 14% in the placebo group (number needed to harm [NNH]=4) and any weight gain was 19% versus 1% in the placebo group (NNH=6).
Other selective serotonin reuptake inhibitors (SSRIs) including fluoxetine, citalopram, and paroxetine were grouped together in 1 SR of 7 RCTs with 383 patients.8 Those with 30% or greater pain reduction at 6 to 16 weeks were 33% versus 23% in the placebo group (NNT=10). Adverse event withdrawals were not different from the placebo group.
Amitriptyline (25 to 50 mg daily): One SR with 4 RCTs and 275 patients found 50% or greater pain reduction at 8 to 24 weeks was achieved in 36% versus 11% in the placebo group (NNT=5). Adverse event withdrawals were not different.8
Limitations of the above findings include small study sizes, uncertain blinding conditions, and minimal reporting of patient function.8
Gabapentinoids
Pregabalin (150 to 600 mg daily in 2 or 3 doses): One SR of 5 RCTs and 3283 patients followed for 8 to 14 weeks found that 150 mg of pregabalin daily was ineffective.9 With doses of 300 to 600 mg daily, there was a 30% or greater pain reduction in about 40% versus 29% in the placebo group (NNT of about 9). Adverse effects increased with increasing doses. Dizziness was experienced by 32% (300 mg) versus 46% (600 mg) versus 10% (placebo) (NNH=3 to 5). Peripheral edema occurred in 6.5% (300 mg) versus 11% (600 mg) versus 2% (placebo) (NNH=11 to 23).
Gabapentin (dose titrated up to 1800 mg daily in 3 doses): One RCT with 150 patients followed for 12 weeks showed a 30% or greater pain reduction in about 51% versus 31% in the placebo group (NNT=5).9 Adverse effects included sedation in about 24% versus 4% in the placebo group and dizziness in 25% versus 9% in the placebo group.
Other pharmacologic management
Opioids and cannabinoids: There is no convincing evidence of benefit and, given the potential harms, these medications should be avoided.10
There are no head-to-head RCTs of gabapentinoids versus antidepressants and no SRs of combination therapy versus single agent therapy.
Practical considerations. Since efficacy for each pharmacologic intervention is similar, the choice of medication should take into account other comorbidities, possible side effects, and cost (Tables 2 and 3).8,9,11
Pharmacologic adverse events
90-day cost comparison of medications
Conclusion
Exercise, antidepressants, and gabapentinoids have roles to play in the management of fibromyalgia. An exercise type of the patient’s choosing shows a modest benefit without evidence of harm. Duloxetine (60 to 120 mg) or mirtazapine (15 to 45 mg) results in 30% or greater reduction in pain in about 50% of patients versus about 35% taking placebo assessed at 7 to 27 weeks. SSRIs and amitriptyline are also likely effective based on limited evidence. Pregabalin (300 to 600 mg) results in 30% or greater pain reduction in about 40% of people versus 29% taking placebo at 8 to 14 weeks. Lower doses (eg, 150 mg) may not be effective; however, higher doses cause more harm, with up to about 30% of people stopping due to side effects. In practice, starting at lower doses and titrating to efficacy is advised. Gabapentin may also be effective at 12 weeks based on limited evidence.
The diagnosis and management of fibromyalgia are best situated in the patient’s medical home. The ability to address the biopsychosocial nature of fibromyalgia and provide continuity of care is central to treatment success. Newer, simplified diagnostic criteria and a range of evidence-based treatments can help empower family physicians and patients to successfully manage this challenging condition.
Notes
Tools for Practice articles are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice{at}cfpc.ca.
Footnotes
Competing interests
None declared
This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to https://www.cfp.ca and click on the Mainpro+ link.
La traduction en français de cet article se trouve à https://www.cfp.ca dans la table des matières du numéro d’avril 2026 à la page e104.
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