Fibromyalgia Medications Compared: What 151 Trials Show

Fibromyalgia Medications Compared: What 151 Trials Show

If you have tried several fibromyalgia medications and none of them made a big difference, you are not alone, and the evidence agrees with you. On 5 October 2026, researchers at McMaster University published the largest comparison of fibromyalgia drug treatments to date in BMJ Medicine.

The Study

The team ran a systematic review and network meta-analysis. That method pools trials that compare drugs with placebo and with each other, so treatments can be ranked even when they were never tested head to head.

• 151 randomised trials with 32,592 participants
• Literature searched up to 13 January 2025
• Prescription drugs, investigational drugs and some supplements (melatonin, vitamin D, vitamin B6, omega-3)
• Each result was compared with a threshold for what patients actually notice, such as a 1.5-point drop on a 0 to 10 pain scale

The Main Finding: Small Benefits at Best

No drug reached the threshold for a clinically important effect on average pain, physical health or mental health. The authors rated almost all of the evidence as low certainty.

That does not mean nothing helps anyone. Some drug classes did better than placebo on specific outcomes:

• More people reporting meaningful improvement: sodium oxybate, noradrenaline reuptake inhibitors (NRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs, such as duloxetine and milnacipran) and gabapentinoids (such as pregabalin). Per 1,000 patients, between 105 and 283 more people reported meaningful improvement or recovery than with placebo.
• At least 30% less pain in a subgroup: for sodium oxybate, NRIs, SNRIs and cyclobenzaprine, between 111 and 202 more people per 1,000 reached this level of pain relief.
• Overall symptom scores: sodium oxybate and SSRIs lowered Fibromyalgia Impact Questionnaire scores by about 8 to 9 points.
• Sleep: tricyclic antidepressants (such as amitriptyline), sodium oxybate and gabapentinoids may improve sleep quality.

No drug increased the risk of stopping treatment or of serious side effects within the trials.

What Did Not Show Benefit

The authors point out that common off-label options, including medical cannabis and low-dose naltrexone, lacked evidence of benefit. Vitamin D had little or no effect on pain. NSAIDs such as ibuprofen gave little or no pain relief. For opioids, the review found no compelling evidence of benefit.

Why the Evidence Is Weak

The authors list several limitations:

• Only 9 of the 151 trials followed patients for longer than six months.
• About 60% of trials were funded by industry.
• Nearly all trials used the 1990 diagnostic criteria, which differ from today's criteria.
• The authors expect the trials overestimate benefit and tolerability compared with daily practice.

What This Means for You

Medication alone rarely transforms fibromyalgia. Most people get a modest benefit in one area, such as sleep or overall wellbeing, rather than a large drop in pain. Response also differs per person: a drug that does little on average can still help you.

This fits the current guidelines, which put exercise, education and sleep at the centre of treatment and treat medication as an addition. The review is part of the BMJ Rapid Recommendations project, so a new guideline based on this work is expected.