Table 1 Characteristics of the systematic reviews included

Thorpe et al., 2018 [18]

To assess the efficacy, safety and tolerability of combination of drugs with monotherapy or placebo, or both, in the treatment of FMS

Double-blind RCT comparing combinations of two or more drugs with placebo or other comparatives, or both, in the treatment of FMS

Single-blind studies, complementary studies to those already selected, non-randomized, studies with other therapies and with patients having diverse fibromyalgia diseases

VAS, NPS, pain reduction of 30% or more and 50% or more, FIQ, NNTH

Sommer et al., 2017 [19]

To assess the efficacy and safety of drugs and non-drug therapy in the treatment of FMS

Randomized clinical trials with drugs used to treat FMS, in databases, non-published articles and specialists’ opinion

Studies with downgraded quality evidence according to the application of the GRADE method used by the authors

50% pain reduction, NNTB, VAS, FIQ

Smith et al., 2011 [20]

To compare the efficacy and harms of drugs used in the treatment of FMS

Studies with patients with FMS, according to the ACR criteria of 1990 and 2010, involving the use of diverse drugs and direct and indirect comparisons, assessing efficacy and damages

Studies with ineligible results, intervention, population, publication and study design

50% pain reduction, MFI, MAF, VAS, FIQ

Häuser et al., 2011 [5]

To assess and compare the efficacy and acceptability of amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) antidepressants in the treatment of FMS

RCT comparing AMT, DLX or MLN with placebo, assessing at least one FMS key domain: pain, sleep, fatigue or health-related quality of life; treatment discontinuation rate

RCTs with combination of drugs with any other treatment

VAS, 30% pain reduction, NPS, NNTB, Cohen’s category, VAS, FIQ

Üçeyler et al., 2008 [22]

To review systematically the efficacy of antidepressants in the treatment of FMS

FMS or CWP diagnosis based on recognized criteria, controlled study design with a control group who received placebo, usual treatment or any other well-defined treatment; treatment with antidepressants, and measurement of specific symptom results

Studies with cyclobenzaprine, which combines characteristics of antidepressant with relaxant, and studies with

S-adenosylmethionine, because this substance is officially available in two countries only (UK and Italy) as food supplement

VAS, tender point count, VAS, BDI, HAM-D, FIQ

Roskell et al., 2011 [6]

To compare pain response to licensed drugs or drugs commonly used in fibromyalgia, also addressing treatment discontinuation due to adverse reactions

Randomized Controlled Clinical Trials with at least 4-week duration with patients aged 18 years or over with clinical FMS diagnosis, using Duloxetine (60 mg / day), Fluoxetine (40 to 50 mg / day), Gabapentin (2400 mg / day), Milnacipran (100 or 200 mg / day), Placebo, Pramipexol (4.5 mg / day), Pregabalin (300 or 450 mg / day), TCA (amitriptyline 25 to 75 mg / day or cyclobenzaprine 1030 mg / day), Tramadol with paracetamol (200 to 300 mg / day)

Treatment of no interest for meta-analysis, no major outcome reported, different treatment doses, study not properly controlled, duplicated or of short duration, poor quality testing and when the article was irretrievable

FIQ, BDI

Häuser et al., 2009 [5]

To determine the efficacy of antidepressants in the treatment of FMS through meta-analysis and randomized controlled clinical trials

Patients effectively diagnosed FMS, RCT with one control group receiving placebo and one group treated with antidepressants (TCA, SSRIs, SNRIs or MAOIs)

Studies assessing cyclobenzaprine, S-adenosylmethionine, or antidepressant combinations. Studies where only categorial data were provided and studies with incomplete data

VAS, FIQ, NRS, HRQOL scale

Perrot et al., 2008 [23]

To review evidences of use of antidepressants in painful rheumatological conditions

Articles published between 1966 and 2007 in 5 European idioms, addressing the use of antidepressants in various rheumatological conditions, including FMS. The authors attributed a rating scale based on the Jadad method (0–5), including studies with scoring above 2

Articles that were scored below 2 in the Jadad scale

VAS, FIQ, NRS