Table 1

Overview of results from selected systematic reviews of placebo-controlled pharmacological trials

(review reference)
No. of trials
(no. of participants)Review quality
Dosages; durations of treatmentOverall trial quality*Safety and comments
Amitriptyline1210 (767) AMSTAR=610–50 mg/day; 8–24 weeksLowThere was no analysis of safety but no difference in discontinuation rates compared with patients on placebo was reported.
Anticonvulsants—pregabalin245 (3256) AMSTAR=10Three studies with fixed doses of 300, 450 and 600 mg/day; one with fixed doses of 150, 300 or 450 mg/day; one flexible dosing study of 300 or 450 mg/day; 8–14 weeksHighIncreased likelihood of withdrawal due to adverse events, RR 1.68, 95% CI 1.36 to 2.07; NNH 12 95% CI 9 to 17. No difference in likelihood of serious adverse events.
Cyclobenzaprine255 (312) AMSTAR=710–40 mg; 2–24 weeksModerateThere was no analysis of adverse outcomes in the trials reviewed although dropout across trials was large (cyclobenzaprine 29%, placebo 43%). Only two studies conducted ITT.
Growth hormone162 (74) AMSTAR=50.0125 mg/kg/day; adjusted to maintain IGF-1 level of 250 ng/mL after first month, 0.0125 mg/kg/day; 9 months to 1 yearNESafety concerns include sleep apnoea and carpal tunnel syndrome.
MAOIs263 (241) AMSTAR=9Pirlindole 150 mg/day, moclobemide 150–300 mg/day; 4–12 weeksLowMAOIs are known to cause potentially fatal hypertensive crises, serotonin syndrome and psychosis when they interact with foods containing tyramine and medications (many of which are commonly used in the treatment of FM), including SSRIs, tricyclic antidepressants and tramadol. The clinical trials had restrictions on concomitant medications.
NSAIDs212 (242) AMSTAR=7Ibuprofen 600 mg four times a day, tenoxicam 20 mg/day; 6–8 weeksLowThe adverse event profile, although not considered in this review, is well established for this class of drugs.
SNRIs—duloxetine316 (2249)AMSTAR=1020–120 mg/day; 12–28 weeksModerateDropout rates due to side effects across studies higher than with placebo. No difference in serious adverse events.
SNRIs—milnacipran305 (4118) AMSTAR=10100 or 200 mg/day; 12–27 weeksHighDropout rates due to side effects across studies were double compared with placebo, but there was no difference in serious adverse events.
SSRIs367 (322) AMSTAR=820–40 mg/day citalopram, 20–80 mg/day fluoxetine, 20–60 mg/day paroxetine; 6–16 weeksModerate to highAcceptability and tolerability were similar to placebo NNH 40, 95% CI 19 to 66. Although several studies excluded patients with depression/anxiety, Häuser et al26 showed a small effect of SSRIs in improving depressed mood (SMD −0.37, 95% CI −0.66 to −0.07).
Sodium oxybate165 (1535) AMSTAR=54.5–6 g/day; 8–14 weeksNEThere is the potential for abuse and central nervous system effects associated with abuse such as seizure, respiratory depression and decreased levels of consciousness.
Tramadol221 (313) AMSTAR=337.5 mg tramadol/325 mg paracetamol 4×/day; 3 monthsHighNo significant difference in discontinuation due to adverse events (RR 1.62, 95% CI 0.94 to 2.80). A high-quality review (AMSTAR score 7) identified a single study, which, among persons who tolerated and benefitted from tramadol, demonstrated a lower discontinuation rate in a double-blind phase compared with placebo.21
  • *According to the method of quality evaluation used in the review.

  • AMSTAR, Assessing the Methodological Quality of Systematic Reviews; FM, fibromyalgia; IGF, insulin growth factor; ITT, intention-to-treat; MAOIs, monoamine oxidase inhibitors; NE, not evaluated; NNH, number needed to harm; NSAIDs, non-steroidal anti-inflammatory drugs; RR, risk ratio; SMD, standardised mean difference; SNRI, serotonin-noradrenalin reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.