Fibromyalgia
Chronic pain syndrome with diffuse muscle pain, pressure hypersensitivity, fatigue, and sleep disturbance. Foundation: graded exercise and CBT; pharmacotherapy: pregabalin, duloxetine, amitriptyline.
ICD-10 M79.74 drugs
Drugs used for this condition
- BAmitriptylineSecond line · Tricyclic antidepressants (TCA)In fibromyalgia low-dose amitriptyline is one recommended drug option: EULAR 2017 gives it a weak recommendation for use, while the only strong recommendation there is exercise; drugs are added when patient education and non-drug measures are insufficient, for severe pain or sleep disturbance. NICE NG193 (2021) suggests considering it among six antidepressants for chronic primary pain and advises against starting gabapentinoids. The Spanish Ministry of Health document Fibromialgia (2011) grades amitriptyline A at 25–50 mg/day at night for pain, sleep and fatigue, whereas Cochrane 2015 found no consistent difference from placebo for sleep or fatigue: the data are third-tier and of very low quality (9 RCTs, 649 participants), with an NNT of 4.1 for halving pain and at least one adverse event in 78% versus 47% (NNH 3.3). The 2025 overview of Cochrane reviews considers the amitriptyline data subject to publication bias. In Spain fibromyalgia is not in section 4.1 of the Tryptizol SmPC, so this is off-label use. The SER 2022 recommendations warn that no drug combination is supported by evidence and that polypharmacy is best avoided. Contraindicated after a recent myocardial infarction, with heart block or arrhythmia, coronary insufficiency, severe liver disease and with MAOIs. Caution in QT prolongation, angle-closure glaucoma, urinary retention and epilepsy; the AGS Beers Criteria 2023 advise older adults to avoid it. With tramadol the risk of seizures and serotonin syndrome increases; fluoxetine, paroxetine and bupropion raise its levels. In patients under 25, antidepressants raise the risk of suicidal behaviour. In pregnancy only when clearly needed; 0.6–1% of the maternal dose passes into breast milk. If there is no benefit after a few weeks, the drug is tapered off.
- BPregabalinFirst line · Gabapentinoids (antiepileptics)Pregabalin is FDA-approved for fibromyalgia (one of three drugs with this indication, alongside duloxetine and milnacipran); in the EU the indication is not registered (the application failed), so in Spain it is off-label. Per EULAR 2017, the only strong-for recommendation in fibromyalgia is exercise; all pharmacotherapy, pregabalin included, is a weak-for adjunct for a specific profile (pain, sleep disturbance). The pain effect is modest (NNT about 8), with a more noticeable effect on sleep. Dose 150–450 mg/day. Risks: dependence and abuse, weight gain, dizziness.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- D5-hydroxytryptophan (5-HTP)Not recommended · Direct serotonin precursor, supplement (not registered as medicine in EU or US)The case for using 5-HTP in fibromyalgia rests on two small Italian trials from the early 1990s: a double-blind study by Caruso (1990) in 50 patients and an open 90-day observation by Sarzi-Puttini (1992). Both reported less pain, lower anxiety and fewer tender points, but the samples were small, both came from the same group, and no independent team has reproduced the results. A systematic overview of complementary therapies for fibromyalgia (Lauche, 2015) places nutritional supplements among approaches with inconsistent and insufficient evidence. Safety is the sharper concern: one report describes 5-HTP taken with sertraline triggering serotonin syndrome that progressed to rhabdomyolysis and compartment syndrome (Patel, 2017), and serotonergic drugs such as duloxetine, milnacipran and amitriptyline are commonly prescribed in fibromyalgia. Benefit in fibromyalgia cannot be considered established, and combining 5-HTP with antidepressants needs medical supervision.
- FGuaifenesinNot recommended · ExpectorantThe guaifenesin protocol for fibromyalgia has been promoted since the 1990s: the theory holds that retained phosphates cause the pain, guaifenesin flushes them out, and a temporary worsening is presented as proof the scheme works. The phosphate hypothesis was never confirmed, and guaifenesin has one indication – productive cough – written into the AEMPS label. The 2017 EULAR recommendations for fibromyalgia do not mention guaifenesin: exercise comes first, then cognitive behavioural therapy, with selected drugs for severe pain or disturbed sleep. The main cost of the protocol is not guaifenesin's adverse effects, which are modest, but the months lost: a person in real pain keeps strict salicylate restrictions in cosmetics and food instead of treatment that works. If guaifenesin has been suggested for fibromyalgia, consider seeking a second opinion from a rheumatologist.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit