Pharmacological Therapies Largely Ineffective Against Fibromyalgia Syndrome Pain

A recent comprehensive overview of Cochrane reviews of pharmacological therapies for adults with fibromyalgia syndrome (FMS) pain has indicated duloxetine, milnacipran, and pregabalin as effective methods of reducing pain intensity.

FMS typically presents heterogeneously and is commonly associated with anxiety and depressive disorders, as well as chronic secondary pain syndromes like inflammatory rheumatic diseases and osteoarthritis. Recently, guidelines have begun recommending a stepwise, graduated approach to treatment, beginning with education, non-pharmacological therapies, and psychological therapies.1

The most utilized psychological therapy is cognitive behavioral therapy (CBT). There is, however, limited evidence of the effectiveness of these treatments, as previous studies have indicated an extremely limited benefit for pain.2

“Pain intensity reduction of 50% or more has been correlated with improvements in comorbid symptoms, function and quality of life for people with chronic pain and FMS,” wrote Andrew Moore, MD, director of Oxford Medical Knowledge and Yealm Community Energy, and colleagues. “An overview of the evidence for these outcomes is relevant for people with FMS and their carers.”1

Moore and colleagues included Cochrane reviews of pharmacological therapies in adults ≥18 years who had been diagnosed with FMS using an established criterion. Reviews involving children or mixed populations that did not report outcomes separately were excluded. Outcomes as close as possible to 3 months (13 weeks) after treatment were prioritized, and those beginning earlier than 1 month (4 weeks) after beginning treatment were not included.1

A total of 49 reviews were initially selected; 27 were excluded after initial screening and 1 after full text assessment. A final total of 21 reviews were included: 7 of these focused on antidepressants including selective serotonin reuptake inhibitors (SSRI), 9 on antiepileptics, and 1 each of NSAIDs, oxycodone, cannabinoids, antipsychotics, and combination therapy. Duloxetine and milnacipran were reviewed separately.1

All included reviews involved RCTs using placebo comparators; most were current or with no planned update. The mean patient age was typically 39-53 years, with ≥85% female. Reviews specified patients with initial pain of at least moderate intensity, typically indicated by a 4 or more on a 0-10 scale.1

Of the included studies, 7 found no trials (carbamazepine, clonazepam, phenytoin, lamotrigine, oxycodone, topiramate, or valproate), 7 had limited and inadequate data (antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide, monoamine oxidase inhibitors, NSAIDs), and 2 were subject to publication bias (amitriptyline, SSRI). Mirtazapine had moderate evidence of no effect, while duloxetine, milnacipran, and pregabalin exhibited moderate to good evidence of substantial pain relief for 4-12 weeks in roughly 1 in 10 adults with moderate or severe FMS pain. Investigators also noted that there were no more significant adverse events than with the placebo.1

Moore and colleagues noted that, of the 21 Cochrane reviews initially selected, only 5 had trustworthy evidence of some or no effect. Impact sizes for the primary outcome of at least 50% pain intensity reduction were modest across the board, with RD values of .09-.14 and NNTs of 6.9-14 compared with placebo. The team also indicated that, although adverse events were relatively common during treatment, serious events were extremely rare.1

“The combination of this overview of pharmacological interventions, together with a previous overview examining non-pharmacological interventions, had data from 31 Cochrane reviews, representing 268 clinical trials and the involvement of over 29,000 patients with FMS,” Moore and colleagues wrote. “It is disappointing to see that 27 of those reviews had no, or inadequate, information that may help guide therapy.”1

References

1. Moore A, Bidonde J, Fisher E, et al. Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: An overview of Cochrane Reviews. Rheumatology. 2024;64(5):2385-2394. doi:10.1093/rheumatology/keae707

2. Williams ACC, Fisher E, Hearn L, Eccleston C. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev. 2020;8(8):CD007407. Published 2020 Aug 12. doi:10.1002/14651858.CD007407.pub4