S-72 Clinical and Expe imen al Rheuma ology 2020
1Ins i u o de Neu ociencias,
Uni e sidad de G anada;
2Depa amen o de Fisio e apia,
Escuela de Ciencias de la Salud,
Uni e sidad de G anada;
3Depa amen o de Psicología,
Uni e sidad de Alme ía, Spain.
Fe nando Rico-Villademo os, PhD
Paula Pos igo-Ma in
Juan M. Ga cia-Lei a, PhD
Jo ge L. O doñez-Ca asco, PhD
Elena P. Caland e, MD, PhD
Please add ess co espondence o:
Elena P. Caland e,
Ins i u o de Neu ociencias,
Uni e sidad de G anada,
A enida del Conocimien o s/n,
18100 A milla, G anada, Spain.
E-mail: epi a@ug .es
Recei ed on No embe 27, 2019; accep ed
in e ised o m on Feb ua y 5, 2020.
Clin Exp Rheuma ol 2020; 38 (Suppl. 123):
S72-S78.
© Copy igh CLINICAL AND
EXPERIMENTAL RHEUMATOLOGY 2020.
Key wo ds: ib omyalgia, ea men
pa e ns, pha macologic,
non-pha macologic, sa is ac ion.
Compe ing in e es s: F. Rico-Villademo os
has ecei ed hono a ia o consul ing,
p o iding medical educa ional se ices,
and/o p o iding medical w i ing se ices
o Almi all, As aZeneca, Eli Lilly, GSK,
Janssen, Lundbeck, O suka, and P ize .
The o he au ho s ha e decla ed
no compe ing in e es s.
ABSTRACT
Objec i e. To e alua e he pa e ns o
ea men among pa ien s wi h ib o-
myalgia (FM) in Spain and o assess
pa ien sa is ac ion and pe cei ed ol-
e abili y o he ea men ecei ed.
Me hods. An obse a ional, c oss-sec-
ional s udy was conduc ed in Spain ia
in e ne om Sep embe 2015 o Ma ch
2017. We eco ded sociodemog aphic
and clinical in o ma ion, including
ea men sa is ac ion e alua ed using a
10-poin nume ical a ing scale (NRS)
and ad e se e en s.
Resul s. E aluable subjec s (n=915)
we e p edominan ly middle-aged, ma -
ied women who p esen ed wi h mod-
e a e o se e e pain, sleep dis u bance
and a ec ed quali y-o -li e. The mos
equen non-pha macologic ea men s
we e physical exe cise (85%), die
(47%), supplemen s such as magnesium
and i amins (47%), and psycho he apy
(31%). The mos equen ly p esc ibed
d ugs we e amadol (40%), benzodi-
azepines (30%), duloxe ine (22%), p e-
gabalin (19%), ami ip yline (17%) and
non-s e oidal an i-in lamma o y d ugs
(NSAIDs; 16%); 7.5% o pa ien s e-
cei ed s onge opioids. A e excluding
benzodiazepines, NSAIDs, and pa ace -
amol, 46% o pa ien s ecei ed ≥2 d ugs.
Sa is ac ion wi h ea men (NRS mean
sco e) was gene ally poo o pha ma-
cologic ea men (4.1), exe cise (4.7),
psycho he apy (5.2), die (5.0), physi-
o he apy (6.2) and acupunc u e (6.3).
The inc ease in he numbe o d ugs
p esc ibed was no associa ed wi h an
inc ease in sa is ac ion, bu a he wi h
an inc ease in ad e se e en s.
Conclusion. Pa ien s wi h FM in Spain
a e o e ea ed wi h a combina ion o
non-pha macologic and pha maco-
logic he apies. Se e al o hese he a-
pies lack adequa e suppo om an-
domised clinical ials and/o clinical
p ac ice guidelines. This o e ea men
is no associa ed wi h ele an clinical
bene i s o pa ien sa is ac ion and, in
he case o pha macologic ea men s,
poses ole abili y and sa e y issues.
In oduc ion
Fib omyalgia (FM) is a cen al sensi i-
sa ion synd ome cha ac e ised by wide-
sp ead pain ha is equen ly accom-
panied by symp oms such as anxie y,
dep ession, sleep dis u bance, a igue
and cogni i e p oblems (1, 2). FM has
a wo ldwide p e alence o 2.7% (3),
p edominan ly a ec ing women wi h
a emale o male a io o 3:1 (3) and,
a e os eoa h i is, is he mos equen
diso de seen in heuma ology clinics
(4). The p esence o como bid condi-
ions, especially o he cen al sensi isa-
ion synd omes (5, 6) and psychia ic
diso de s (7), is e y equen . FM is
associa ed wi h a subs an ial bu den o
he indi idual and socie y (8-12).
I is gene ally ag eed ha he manage-
men o FM equi es a mul idisciplina y
app oach, combining non-pha maco-
logic ea men s as he ini ial app oach,
mainly educa ion, exe cise and psycho-
he apy, and beginning pha macologic
ea men s he ea e (13, 14). Among
pha macologic ea men s, based on he
esul s om clinical ials, he guide-
lines ecommend p egabalin, dulox-
e ine, milnacip an, ami ip yline, cy-
clobenzap ine and, in ce ain pa ien s,
amadol as he apeu ic op ions (13, 14).
In addi ion o ole abili y issues, none o
hese d ugs imp o es all symp oma ic
domains o he disease, exhibi s a la ge
e ec on he symp oms o has consis -
en ly demons a ed a g ea e o e all e -
icacy compa ed wi h he o he s (15).
Da a om clinical p ac ice also e lec s
his impo an limi a ion o he pha ma-
Pa e ns o pha macologic and non-pha macologic
ea men , ea men sa is ac ion and pe cei ed ole abili y
in pa ien s wi h ib omyalgia: a pa ien s’ su ey
F. Rico-Villademo os1, P. Pos igo-Ma in2, J.M. Ga cia-Lei a1,
J.L. O doñez-Ca asco3, E.P. Caland e1
Rico-Villademo os, F., Pos igo-Ma in, P., Ga cia-Lei a, J. M., O doñez-Ca asco, J. L., & Caland e, E. P. (2020). Pa e ns o
pha macologic and non-pha macologic ea men , ea men sa is ac ion and pe cei ed ole abili y in pa ien s wi h ib omyalgia:
a pa ien s' su ey.
Clinical and expe imen al heuma ology, 38 Suppl 123
(1), 72–78. h ps://www.clinexp heuma ol.o g/
a icle.asp?a=15028
S-73
Clinical and Expe imen al Rheuma ology 2020
a e ns o ea men in ib omyalgia ioillaemo os e al
cologic ea men s o FM. Acco ding o
a ecen s udy unde aken in USA, a -
e one yea o ini ia ing pha macologic
ea men , only 25% o he pa ien s con-
inue wi h he ini ial op ion, which e-
qui es swi ching he medica ion, a com-
bina ion wi h ano he d ug o simply a
ea men discon inua ion (16). Consis -
en wi h his inding, i has been epo -
ed ha less han hal o he pa ien s wi h
FM a e sa is ied wi h he medica ion
hey a e ecei ing (17). In addi ion, i
also appea s ha an impo an p opo -
ion o pa ien s wi h FM do no ecei e
app op ia e ea men and ha ea men
adhe ence is poo (16). A wide a ie y
o non-pha macologic ea men s a e
used in he clinical p ac ice in pa ien s
wi h FM (9, 17-22), and al hough he
in o ma ion is e y limi ed, pe cei ed
e ec i eness and sa is ac ion wi h hese
he apies a e also poo (9, 22).
O e all, wi h he excep ion o a su ey
conduc ed in La in Ame ica and Eu ope
(20) and a ecen s udy conduc ed in he
Uni ed Kingdom (22), mos o he in-
o ma ion we ha e on he pa e ns o
ea men and pa ien pe cep ions o
hose ea men s comes om s udies
conduc ed in USA, and da a on ea -
men sa is ac ion as well as pa ien pe -
cep ion o ole abili y a e limi ed. This
s udy aimed o e alua e he pa e ns
o ea men among pa ien s wi h FM
in Spain and o assess pa ien sa is ac-
ion and pe cei ed ole abili y wi h he
ea men ecei ed.
Ma e ials and me hods
S udy design
This was an obse a ional, c oss-sec-
ional s udy conduc ed in Spain be-
ween Sep embe 2015 o Ma ch 2017.
Pa icipa ion in he su ey was solici -
ed h ough se e al pa ien associa ions
in e e y egion o Spain and di usion
h ough social ne wo ks. Pa icipan s
we e b ie ly in o med a he beginning
o he su ey o i s objec i es and ha
hey should be aged 18 o olde and
ha e been diagnosed wi h FM; due o
he na u e o he su ey, diagnosis e-
lied on pa ien s’ epo and could no be
con i med by he s udy in es iga o s.
Pa icipan s we e also in o med ha
answe ing he su ey was equi alen
o consen o pa icipa e in he s udy
and ha hei da a would be used o
in es iga ional pu poses. Since he
ques ionnai e was anonymous, no w i -
en in o med consen was equi ed. The
s udy was app o ed by he Human Re-
sea ch E hics Commi ee o he Uni e -
si y o G anada.
The su ey consis ed o i e blocks o
ques ions (i is a ailable a h p://goo.
gl/ o ms/UAO7RKC6ks. See Annex
1 o an English ansla ion o he su -
ey): sociodemog aphic in o ma ion,
clinical da a, da a on pha macologic
ea men s, da a on non-pha macologic
ea men s, and an assessmen o pa-
ien sa is ac ion wi h ea men . Soci-
odemog aphic da a included age, sex,
ma i al s a us, educa ional le el, and
employmen s a us. Clinical da a com-
p ised in o ma ion on du a ion o diag-
nosis, como bidi ies, and i e ques ions
ha used a 10-poin nume ical a ing
sco e (NRS) o e alua e he impac o
he disease on daily li e, pain in ensi y,
sleep quali y, le el o dep ession and
le el o anxie y. Excep o he sleep
scale, he g ea e he sco e, he g ea e
he impac o symp om; he e e se was
applicable o he sleep a ing scale.
Da a on pha macologic ea men in-
cluded who p esc ibed he ea men ;
medica ions and dosage ha he pa ien
was cu en ly ecei ing; whe he he
pa ien was aking any i amin, sup-
plemen , p obio ic/p ebio ic o any al-
e na i e na u al/he bal medicines; and
whe he he pa ien s expe ienced any
dis u bances associa ed wi h he cu -
en ea men . Da a on non-pha maco-
logic ea men included in o ma ion on
physical exe cise ( ype and equency),
psycho he apy ( ype and equency),
die , and an open ques ion on o he
ea men s. Finally, pa ien sa is ac ion
wi h ea men was e alua ed wi h a
10-poin NRS whe e 1 indica ed a lack
o sa is ac ion and 10 ha he pa ien
was comple ely sa is ied; he e we e 5
NRS, one o each ype o ea men .
Da a analysis
The s a is ical analyses we e mos ly de-
sc ip i e, using means and s anda d de-
ia ion o quan i a i e a iables and ab-
solu e and ela i e equencies o quali-
a i e a iables. Di e ence in he mean
sa is ac ion acco ding o he numbe o
d ugs ecei ed was analysed using one-
way analysis o a iance (ANOVA).
Mean sa is ac ion o each non-pha ma-
cologic ea men was compa ed wi h
he mean sa is ac ion o pha macologic
ea men using an unpai ed es . We
pe o med wo explo a o y mul iple
linea eg ession analyses. In he i s
model, ea men sa is ac ion as e alu-
a ed wi h he NRS was he dependen
a iable and he independen a iables
we e age (yea s), sex, ime om diag-
nosis (ca ego ised as <1 yea , 1-5 yea s
and >1yea ), numbe o diseases asso-
cia ed wi h FM, pe o ming physical
exe cise, ecei ing psychological ea -
men , ecei ing die e ic ea men , num-
be o d ugs ecei ed, p esence o side-
e ec s, and he sco es in he NRS o
pain in ensi y, sleep quali y, dep essi e
symp oma ology and anxious symp om-
a ology. In he second model, pe o med
only in pa ien s who we e ecei ing
pha macologic ea men , he depend-
en a iable was he sco e in he NRS o
impac on daily-li e and he independen
a iables we e he same as in he i s
model. All compa isons we e wo- ailed
and conside ed signi ican i p<0.05. All
analyses we e pe o med using IBM
SPSS S a is ics o Windows, . 25.0.
(A monk, NY: IBM Co p).
Resul s
O e all, 1,166 subjec s esponded o he
ques ionnai e. A e emo ing dupli-
ca es (n=103) and ques ionnai es om
coun ies o he han Spain (n=148), we
Table I. Demog aphic cha ac e is ics.
Cha ac e is ic n=915
Age (yea s), mean (SD) 47.0 (9.3)
Sex ( emale), n (%) 866 (94.6)
Ma i al s a us, n (%)
Ma ied/li ing wi h a pa ne 625 (68.3)
Di o ced 141 (15.4)
Single 127 (13.9)
Widowed 22 (2.4)
Employmen s a us, n (%)
Employed 338 (36.9)
Housewo k 154 (16.8)
Disabled 88 (9.6)
Unemployed 195 (21.3)
S uden 9 (1.0)
Re i ed (age) 17 (1.9)
Re i ed (disease) 114 (12.5)
n: numbe o pa ien s; SD: s anda d de ia ion.
S-74 Clinical and Expe imen al Rheuma ology 2020
a e ns o ea men in ib omyalgia ioillaemo os e al
had 915 e aluable ques ionnai es. Sub-
jec s we e p edominan ly middle-aged,
ma ied women (Table I). Pa ien s had
an es ablished diagnosis o FM o mo e
han 5 yea s and exhibi ed mode a e o
se e e pain, sleep dis u bance and an
impac on daily li e (Table II); hey also
p esen ed wi h a high numbe o co-
mo bidi ies, mainly wi h o he cen al
sensi isa ion en i ies, psychia ic diso -
de s and musculoskele al diso de s.
Non-pha macologic ea men
The mos equen non-pha macologic
ea men was physical exe cise (85%),
mos commonly walking (66%) (Table
III); 33% o he pa icipan s pe o med
physical exe cise mo e han 3 days in a
week and 44% o pa ien s 2–3 days pe
week. A speci ic die was ollowed by
almos hal o he pa icipan s, wi h hy-
pocalo ic and glu en- ee die s used mos
equen ly. Almos hal o he pa ici-
pan s we e aking supplemen s, mainly
magnesium and se e al kinds o i a-
mins. Finally, only one- hi d o pa ien s
we e ecei ing psycho he apy; howe e ,
he majo i y o such pa icipan s (73%)
ecei ed i less han 1 day a week.
Pha macologic ea men
Pha macologic ea men was ecei ed
by 87% o pa icipan s and was p e-
sc ibed in almos hal o he pa icipan s
by a amily physician alone (18.3%), a
heuma ologis alone (15.1%) o bo h
specialis s (14.7%) (Supplemen a y
Fig. 1). O e all and ega dless o he co-
p esc ibe s, he mos equen p esc ib-
e s we e a amily physician (58.8%), a
heuma ologis (56.3%), a psychia is
(33.3%) and a pain physician (20.0%).
The mos equen ly p esc ibed d ugs
we e amadol (40%) and benzodiaz-
epines (30%) and o a lesse ex en du-
loxe ine (22%), p egabalin (19%), ami-
ip yline (17%) and NSAIDs (16%);
7.5% o pa icipan s ecei ed o he
opioids di e en om amadol (Table
IV). When only conside ing d ugs o
he ea men o FM suppo ed by a
leas one andomised clinical ial (i.e.
excluding benzodiazepines, NSAIDs,
and pa ace amol), 46% o pa icipan s
we e ecei ing wo o mo e d ugs and
he mos equen ly used d ug was
amadol, ei he used as mono he apy o
in combina ion (Table IV). Mean d ug
dosages a e also p esen ed in Table IV.
The e we e some di e ences when he
single p esc ibe was a heuma ologis
(n=135) o a amily physician (n=188).
Among pa icipan s whose pha ma-
cologic ea men was p esc ibed by
a heuma ologis , he e was a highe
equency o p esc ip ion o amadol
(40% s. 32%), duloxe ine (22% s.
15%), ami ip yline (22% s. 14%),
p egabalin (17% s. 13%), NSAIDs
(16% s. 13%), o he opioids (11% s.
5%), and luoxe ine (10% s. 6%); in
con as , hey showed a lowe p esc ip-
ion equency o pa ace amol (4% s.
7%) and pa oxe ine (4% s. 7%), (da a
Table II. Cha ac e is ics o he disease.
Cha ac e is ic n=915
Time since diagnosis, n (%)
<1 yea 111 (12.1)
1-5 yea s 267 (29.2)
>5 yea s 537 (58.7)
Associa ed symp omsa, mean (SD)
Pain in ensi y 7.2 (2.0)
Sleep quali y 3.4 (2.3)
Dep ession 5.8 (2.7)
Anxie y 6.3 (2.6)
Impac on daily li e, mean (SD) 7.7 (2.1)
F equen (≥5%) como bid diseases, n (%)
Anxie y diso de 555 (60.7)
Ch onic a igue synd ome 539 (58.9)
Dep essi e diso de 496 (54.2)
I i able bowel synd ome 448 (49.0)
A h osis 400 (43.7)
Tension- ype headache 374 (40.9)
Mig aine 383 (41.9)
Tempo omandibula dys unc ion 346 (37.8)
In e s i ial cys i is 144 (15.7)
Rheuma oid a h i is 143 (15.6)
Mul iple chemical sensi i i y 120 (13.1)
synd ome
Disc he nia ion 65 (7.1)
aAll symp oms we e e alua ed in a NRS (1-10);
he g ea e he sco e, he poo e he clinical s a-
us, excep o sleep quali y, o which he e-
e se was applicable.
n: numbe o pa ien s; SD: s anda d de ia ion.
Fig. 1. T ea men sa is ac ion wi h pha macologic and non-pha macologic ea men s o ib omyalgia.
*p<0.0001 s. o e all pha macologic ea men .
Table III. Mos equen (≥5%) ypes o
non-pha macologic ea men .
Type o ea men an (%)
Physical exe cise 777 (84.9)
Walking 604 (66.0)
Swimming 119 (13.0)
Pila es 83 (9.1)
Cycling 68 (7.4)
Supe ised Gym 50 (5.5)
Die 432 (47.2)
Hypocalo ic 155 (16.9)
Glu en- ee 121 (13.2)
Supplemen s 427 (46.7)
Magnesium 177 (19.3)
Vi amin D 76 (8.3)
Complex B Vi amins 68 (7.4)
Mul i i amin complex 62 (6.8)
Vi amin B12 52 (5.7)
Psycho he apy 287 (31.4)
Cogni i e beha iou al he apy 140 (15.3)
Relaxa ion echniques 112 (12.2)
Mind-body he apy 52 (5.7)
aPa ien s could be ecei ing se e al ea men s.
S-75
Clinical and Expe imen al Rheuma ology 2020
a e ns o ea men in ib omyalgia ioillaemo os e al
on di e ences o less han 3% a e no
epo ed he ein).
T ea men sa is ac ion and
ad e se e en s
Rega dless o he ea men modali y,
sa is ac ion was low (Fig. 1) bu was
signi ican ly highe o any non-pha -
macologic app oach han o pha ma-
cologic ea men s. Wi h a sco e o e
6.0 in he 10-poin NRS, acupunc u e
and physio he apy we e he in e en-
ions associa ed wi h he highes sa -
is ac ion. The inc ease in he numbe
o d ugs p esc ibed o he ea men
o FM was no associa ed wi h s a is i-
cally signi ican inc ease in sa is ac ion
(Fig. 1). Sa is ac ion did no g ea ly
di e be ween d ugs used as mono-
he apy wi h a mean (SD) sco e in he
10-poin NRS o 4.1 (2.2) o amadol,
3.9 (2.2) o ami ip yline, 3.6 (1.7) o
duloxe ine, and 3.5 (2.1) o p egaba-
lin. The use o amadol in pa icipan s
ecei ing combina ion he apy was as-
socia ed wi h a sligh inc ease o sa -
is ac ion when combined wi h ano he
d ug (wi h amadol 4.6 [2.3] s. wi h-
ou amadol 4.1 [2.3]) bu emained
he same when used in poly he apy
(wi h amadol 4.3 [2.2] s. wi hou
amadol 4.2 [2.0]).
Ad e se e en s we e common and in-
c eased as he numbe o cop esc ibed
d ugs inc eased (Table V). In gene al,
he ype o side e ec was conco dan
wi h he ad e se eac ion p o ile o he
mos equen ly p esc ibed d ugs.
Explo a o y mul i a ia e analysis
The only ac o nega i ely associa ed
wi h ea men sa is ac ion was he p es-
ence o side-e ec s (β=-0.138, p<0.001).
The ac o s posi i ely associa ed wi h
ea men sa is ac ion we e he sco e in
he sleep quali y (β=0.236, p<0.001)
and he sco e in pain in ensi y (β=0.087,
p=0.049). The numbe o p esc ibed
d ugs was no associa ed wi h ea men
sa is ac ion (β=0.031, p=0.414).
The ac o s associa ed wi h a g ea e
impac on daily li e we e pain in en-
si y (β=0.736, p<0.001), se e i y o
anxious symp oma ology (β=0.084,
p=0.017), ime om diagnosis
(β=0.046, p=0.049), and being male
(β=0.048, p=0.028). The only ac o
associa ed wi h lesse impac on daily
li e was pe o ming physical exe cise
(β=-0.044, p=0.049).
Discussion
These esul s indica e ha pa ien s wi h
FM in Spain a e usually ea ed wi h a
combina ion o d ugs and non-pha -
macologic s a egies. Sa is ac ion wi h
mos ea men app oaches is poo , and
he ea men ha pa ien s a e ecei -
ing appea s inadequa e in a subs an ial
p opo ion o pa ien s due o he ol-
lowing easons: o e use o amadol
and s onge opioids, use o low doses
o some d ugs such as p egabalin, use
o polypha macy wi hou inc easing
ea men sa is ac ion bu inc easing
ad e se e en s, inconsis en use o e -
ec i e non-pha macologic app oaches
such psycho he apy, and use o he a-
pies ha lack p o en e ec i eness
such as die s, magnesium o i amins.
In con as , exe cise was a gene alised
p ac ice among hese pa ien s.
Ou s udy has se e al limi a ions ha
should be conside ed when in e p e ing
he esul s. Fi s , we used a c oss-sec-
ional design which, al hough adequa e
o e alua ing p esc ip ion pa e ns, is
subjec ed o su i al bias. Tha is, only
pa ien s who con inue wi h he p e-
sc ibed ea men (i.e. hose wi h be e
e icacy and/o ole abili y esul s) we e
cap u ed by ou s udy. In o he wo ds,
we had an op imis ic snapsho o ea -
Table IV. Mos equen (≥5%) pha macological ea men .
D ug n (%) Daily dose (mg/day), mean (SD)
O e all (n=915)
T amadol 368 (40.2) 190.90 (127.1)
Benzodiazepinea276 (30.2) NA
Duloxe ine 204 (22.3) 69.72 (51.2)
P egabalin 176 19.2) 161.41 (109.4)
Ami ip yline 157 (17.2) 32.88 (24.7
NSAIDsa143 (15.6) NA
Pa ace amola93 (10.2) NA
Fluoxe ine 84 (9.2) 32.00 (25.6)
T azodone 77 (8.4) 95.48 (42.8)
O he opioidsa69 (7.5) NA
Gabapen in 58 (6.3) 902.55 (589.4)
Pa oxe ine 54 (5.90) 26.33 (10.7)
Cyclobenzap ine 51 (5.6) 28.33 (40.0)
Venla axine 50 (5.5) 182.75 (104.0)
Esci alop am 47 (5.1) 18.38 (10.1)
By numbe o d ugs (n=915),b
One d ug 295 (32.2)
T amadol 92 (10.1)
Duloxe ine 52 (5.7)
Ami ip yline 41 (4.5)
P egabalin 31 (3.4)
Fluoxe ine 18 (2.0)
Two d ugs 219 (23.9)
Duloxe ine+ amadol 28 (3.1)
Ami ip yline+ amadol 18 (2.0)
Fluoxe ine+ amadol 14 (1.5)
P egabalin+ amadol 12 (1.3)
Duloxe ine+p egabalin 12 (1.3)
Th ee d ugs 149 (16.3)
Duloxe ine+p egabalin+ amadol 12 (1.3)
Duloxe ine+ azodone+ amadol 8 (0.9)
Fou d ugs 42 (4.6)
≥Fi e d ugs 15 (1,6)
n: numbe o pa ien s; NA: no applicable; SD: s anda d de ia ion.
aEach ca ego y comp ises se e al d ugs o combina ions o d ugs and he e o e, no mean dose can be
calcula ed.
bFo hese analyses we only conside ed d ugs o he ea men o ib omyalgia suppo ed by a leas
one andomised clinical ial (i.e. benzodiazepines, non-s e oidal an i-in lamma o ies, and pa ace amol
we e excluded).
S-76 Clinical and Expe imen al Rheuma ology 2020
a e ns o ea men in ib omyalgia ioillaemo os e al
men . The c oss-sec ional design and
he lack o in o ma ion on o he impo -
an a iables (e.g. a igue o cogni ion)
make ha ou mul i a ia e analyses o
ac o s associa ed wi h ea men sa is-
ac ion and wi h he impac on daily li e
can only be conside ed explo a o y. The
sou ce o da a we e people awa e o he
su ey h ough pa ien associa ions and
social ne wo ks; his is likely o a ec
he ep esen a i eness o ou sample,
which p obably includes pa ien s wi h
g ea e awa eness o he disease. We
belie e ha o a ce ain ex en , his
could ha e also con ibu ed o cap u e
an op imis ic snapsho . I is impo an
o pe o m u he s udies wi h a mo e
ep esen a i e sample o pa ien s wi h
FM ec ui ed om he gene al popula-
ion. The diagnosis o FM was sel - e-
po ed and due o he anonymous na u e
o he s udy could no be con i med by
a membe o he esea ch eam. Finally,
ou su ey was conduc ed in a single
Eu opean coun y, hus con ibu ing o
he limi a ions o i s ep esen a i eness.
Pha macologic ea men s a e domina -
ed by amadol, ei he as a mono he apy
o combina ion he apy. This p obably
e lec s he se e i y o pain and associ-
a ed disabili y in hese pa ien s, as well
as he gene al limi a ion o all a ailable
pha macologic ea men s o amelio-
a ing pain. I should be bea in mind
ha , al hough only pe o med as an ex-
plo a o y analysis, he s onges ac o
associa ed wi h a g ea e impac on dai-
ly li e was pain in ensi y; hus, o each
poin inc ease in he sco e o pain in en-
si y, he sco e in he impac on daily li e
inc eased o e 0.7 poin s. In addi ion,
no only was amadol he p edominan
pha macologic app oach, bu he use
o s onge opioids was also ela i ely
equen (7.5%), and in app oxima ely
20% o he pa icipan s, pain uni s we e
in ol ed in pha macologic manage-
men . This equen use o amadol has
been consis en ly epo ed in s udies
conduc ed in he US ac oss he las 10
yea s (9, 16, 17, 23). In Eu ope, a ecen
su ey conduc ed in he UK showed
ha codeine and amadol we e among
he 5 mo e commonly ied d ugs in pa-
ien s wi h FM (22). In ou iew, his
use o amadol is no jus i ied by he
e idence, which is limi ed o wo an-
domised con olled ials e alua ing i s
e ec on pain when adminis e ed o ally
as mono he apy (24) o in combina-
ion wi h pa ace amol (25). Howe e ,
ou esul s also indica e ha , al hough
ea men sa is ac ion was gene ally
poo , amadol was associa ed wi h a
sligh ly highe sa is ac ion han o he
d ugs. We belie e ha his esul is like-
ly o e lec he be e esul s ob ained
on pain wi h amadol han wi h o he
d ugs. The e ec o amadol is limi ed
o pain and he e o e i s use as a mono-
he apy is di icul o jus i y. The use o
o he s onge opioids was lowe han
ha epo ed in he US (9, 17) bu was
ne e heless high (7.5%) indica ing ha
he abuse o opioids o ea ing ch on-
ic pain is a p oblem no limi ed o he
US bu also appea s o a ec Eu opean
coun ies such as Spain o , as shown in
a ecen su ey, he UK (22). Acco ding
o he Cen e o Disease and P e en-
ion guidelines o he use o opioids in
ch onic pain, hey only should be used
when bene i s o pain and unc ion a e
expec ed o ou weigh he isks a he
lowes e ec i e dose and hei con-
inua ion should be ee alua ed e e y
h ee mon hs, among o he ecommen-
da ions (26). Unde hese condi ions,
i is unlikely ha opioids could play a
signi ican ole in pa ien s wi h FM. In
ou iew, i he ini ial ea men o he
amelio a ion o pain ailed, he combi-
na ion o p egabalin wi h ei he dulox-
e ine o , whe e a ailable, milnacip an
as well as he combina ion o low doses
o ami ip yline wi h an an idep essan
o wi h mela onin a e be e al e na i es
han opioids wi h some suppo om
clinical ials (27-31). The addi ion o
NSAIDs o he s anda d ea men is
no associa ed wi h an addi ional clini-
cal bene i on pain (32, 33) and should
no be ecommended.
As men ioned in he in oduc ion, he
e ec s o a ailable e idence-based
d ugs o he ea men o FM (namely,
duloxe ine, milnacip an, ami ip yline,
cyclobenzap ine, p egabalin, and am-
adol) a e limi ed o a ew symp oms and
a e usually small o doub ul in hei
clinical ele ance (15, 34). The e o e,
al hough he e idence on combina ions
o d ugs o he ea men o FM is a
om being obus (35), i is no su p is-
ing ha pa ien s equi ed mo e han one
pha macologic ea men . Fu he on
he use ulness o combina ion he apy
o pain, which has been ecen ly ana-
lysed in a sys ema ic e iew (35), he
use o some combina ions, such as mel-
a onin and ami ip yline, luoxe ine and
ami ip yline, and p egabalin and du-
loxe ine, has also been associa ed wi h
g ea e o e all imp o emen compa ed
o mono he apy (27, 28, 30, 31) and in
some epo s, o a g ea e bene i on he
quali y o li e (28, 31). In ou s udy,
he combina ion o ami ip yline wi h
mela onin was used in 1 pa icipan
and wi h luoxe ine in 4 pa icipan s,
and he combina ion o duloxe ine and
p egabalin was used in 12 pa icipan s.
Bea ing in mind ha 24% o pa ien s
we e ecei ing wo d ugs, ou esul s
indica e ha mos pa ien s ecei e com-
bina ions ha lack he suppo o any
andomised clinical ial. Nea ly 22%
o pa icipan s we e ecei ing h ee o
mo e d ugs wi hou exhibi ing highe
sa is ac ion (nei he in he bi a ia e
analysis, no in he mul i a ia e analy-
sis) and p esen ed wi h mo e ad e se
e en s han hose who we e ecei ing
Table V. Ad e se e en s o e all and by numbe o d ugs.
Sys em o gan/side-e ec s, n (%) O e all 1 D ug 2 D ugs 3 D ugs ≥4 D ugs
n=720 n=295 n=219 n=149 n=57
Gas oin es inal side-e ec 358 (49.7) 124 (41.9) 116 (53.0) 76 (51.0) 42 (73.7)
Nausea/ omi ing 167 (23.2) 66 (22.3) 54 (24.7) 29 (19.5) 18 (31.6)
Abdominal pain/hea bu n 142 (19.7) 45 (15.3) 43 (19.6) 35 (23.5) 19 (33.3)
Cons ipa ion/dia hoea 49 (6.8) 13 (4.4) 19 (8.7) 12 (8.1) 5 (8.8)
Cen al ne ous sys em side-e ec 404 (56.1) 145 (49.0) 119 (54.3) 91 (61.1) 49 (86.0)
Somnolence/seda ion/ a igue 166 (23.1) 56 (19.0) 54 (24.7) 37 (24.8) 19 (33.3)
Dizziness/ e igo 118 (16.4) 43 (14.6) 36 (16.4) 26 (17.4) 13 (22.8)
Anxie y/ne ousness/i i abili y 31 (4.3) 13 (4.4) 8 (3.6) 3 (2,0) 7 (12.3)
Cogni i e impai men 45 (6.3) 15 (5.1) 9 (4.1) 14 (9.4) 7 (12.3)
O he o gans/sys ems side-e ec s 93 (12.9) 33 (11.2) 15 (6.9) 29 (26.2) 16 (28.1)
S-77
Clinical and Expe imen al Rheuma ology 2020
a e ns o ea men in ib omyalgia ioillaemo os e al
wo d ugs. Thus, his polypha macy,
in addi ion o no being suppo ed by
esea ch e idence, does no appea o
be clinically jus i ied and should be
a oided. In addi ion o wo sening ole -
abili y, polypha macy in hese pa ien s
inc eases he isk o d ug-d ug in e ac-
ions, especially i we ake in o con-
side a ion ha many o he p esc ibed
d ugs a e inhibi o s and/o subs a es o
CYP2D6 o he cy och ome P450 (36).
Sa is ac ion wi h pha macologic ea -
men was e y poo ega dless o he
d ugs o whe he hey we e used as
mono he apy o in combina ion and
was poo e han non-pha macologic ap-
p oaches. This is somewha consis en
wi h he esul s o he su ey conduc ed
in UK whe e, al hough e ec i eness o
bo h ypes o in e en ion we e simi-
la , accep abili y, measu ed as he a io
be ween e ec i eness and ole abili y,
was highe wi h non-pha macologic
app oaches (22). Ou esul s ega ding
sa is ac ion a e especially ema kable
since, due o ou design, we cap u ed
in o ma ion on pa ien s who a e ole -
a ing he d ug and p obably exhibi ing
he g ea es long- e m e icacy; ha is,
as men ioned abo e, we a e looking a
he bes possible scena io. The ac ha
sa is ac ion wi h pha macologic ea -
men s was consis en ly lowe han wi h
any o he ype o non-pha macologic
ea men ein o ces he impo ance
o enhancing he p esc ip ion o hose
non-pha macologic app oaches which
a e suppo ed by enough e idence such
as some o ms o exe cise (i.e. ae obic
o s eng hening exe cise) (37, 38) and
psycho he apies (i.e. cogni i e-beha -
iou al and, possibly, mind ulness-based
in e en ions) (39, 40). Psycho he apy
appea s unde used, bea ing in mind he
need o inco po a e coping s a egies by
hese pa ien s and he high p opo ion
o pa ien s who exhibi ed anxie y o de-
p essi e symp oms; un o una ely, his
ype o he apy is no ully inco po a ed
in o he Spanish na ional heal h sys em.
Con e sely, supplemen s appea o be
o e used since he e is no e idence ha
suppo s such equen use o magne-
sium, i amins o o he complemen a y
emedies (41, 42). This o e use o sup-
plemen s could be ela ed o sel -p e-
sc ip ion p ac ices; howe e , i is likely
ha nu ses and physicians could also
con ibu e o his p ac ice (43). Die s
we e equen ly used in ou s udy. Die s
could ha e a non-speci ic bene icial im-
pac on some symp oms (e.g. gas oin-
es inal) (39), and could possibly be ec-
ommended o some selec ed pa ien s
bu no o he ex en as was seen in ou
s udy. Howe e , in some pa ien s, die
and exe cise could be pa o a pe sonal
s a egy o ha ing a heal hy li es yle,
and as such, is welcomed. O e all, he
equen use o complemen a y ea -
men s in ou sample is consis en wi h
he esul s o o he s udies (9, 19) and
could be ela ed wi h he high le els o
pain and disabili y (18).
In e es ingly, al hough he sample size
was small, he in e en ions associa ed
wi h he highes sa is ac ion we e acu-
punc u e and physio he apy. Acupunc-
u e added o he s anda d ea men has
been shown o be e ec i e in educing
pain in pa ien s wi h FM and is well-
ole a ed, and hus is included among
he ecommended ea men op ions in
he EULAR guidelines (14). The e-
sul s ega ding physio he apy a e di -
icul o in e p e since i was assessed
by an answe o an open-ended ques ion
(“o he ea men s”) and he e o e, i is
likely o include a a ie y o physical
in e en ions. A ecen o e iew o sys-
ema ic e iews conside ed ha only
low o mode a e in ensi y endu ance
and s eng h aining a e ecommended
(44); in ac , EULAR guidelines ecom-
mend agains he use o some ypes o
physical he apies, such as chi op ac ic
ca e and massage, while s ongly ec-
ommending ae obic and s eng hen-
ing exe cises (14). We belie e ha he
g ea e sa is ac ion wi h acupunc u e,
physio he apy and o he non-pha ma-
cologic app oaches is likely o be e-
la ed o hei imp o ed ole abili y o e
pha macologic ea men s and hus,
hei be e bene i - isk a ios.
In conclusion, pa ien s wi h FM in
Spain a e o e ea ed wi h a combina-
ion o non-pha macologic and pha ma-
cologic he apies, and se e al o hese
he apies lack adequa e suppo om
andomised clinical ials and/o clini-
cal p ac ice guidelines. This o e ea -
men is no associa ed wi h any ele an
clinical bene i o pa ien sa is ac ion
and, in he case o pha macologic ea -
men s, poses ole abili y and sa e y
issues. O e all, he e is a wide oom
o imp o emen in he managemen
o hese pa ien s by all he s akehold-
e s in ol ed: physicians imp o ing
he a ional use o d ugs and o he in-
e en ions, and p o iding a be e pa-
ien educa ion on hei disease and i s
he apeu ic al e na i es; pa ien s a oid-
ing he use o supplemen s and o he
complemen a y he apies ha lack o
su icien e idence and ini ia ing o
enhancing heal hy habi s (e.g. ae obic
exe cise); heal hca e manage s imp o -
ing access o he ew e idence-based
e ec i e he apeu ic al e na i es (e.g.
psycho he apy); and na ional heal h
au ho i ies and o ganisa ions p o iding
unding o esea ch a ou ing he in-
clusion o he sea ch o and e alua ion
o new he apeu ic, possibly mul imod-
al, al e na i es o hese pa ien s in he
esea ch agenda.
Acknowledgemen s
We g ea ly hank he anonymous pa -
icipa ion o he Spanish pa ien s as-
socia ions on FM and he pa ien s who
comple ed his su ey. We also hank
Co alie Mai ie o a p elimina y analy-
sis o his su ey.
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