Ci a ion: Mon ejo, A.L.; Sánchez-
Sánchez, F.; De Ala cón, R.; Ma ías, J.;
Co és, B.; Ma os, C.; Ma ín-Pin o, T.;
Ríos, P.; González-Ga cía, N.; Acos a,
J.M. Swi ching o Vo ioxe ine in
Pa ien s wi h Poo ly Tole a ed
An idep essan -Rela ed Sexual
Dys unc ion in Clinical P ac ice: A
3-Mon h P ospec i e Real-Li e S udy.
J. Clin. Med. 2024,13, 546. h ps://
doi.o g/10.3390/jcm13020546
Academic Edi o : Ana Adan
Recei ed: 28 No embe 2023
Re ised: 13 Janua y 2024
Accep ed: 16 Janua y 2024
Published: 18 Janua y 2024
Copy igh : © 2024 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
Jou nal o
Clinical Medicine
A icle
Swi ching o Vo ioxe ine in Pa ien s wi h Poo ly Tole a ed
An idep essan -Rela ed Sexual Dys unc ion in Clinical P ac ice:
A 3-Mon h P ospec i e Real-Li e S udy
Angel L. Mon ejo 1,2,3,* , F oilán Sánchez-Sánchez 4, Rubén De Ala cón2, Juan Ma ías 2, Benjamin Co és2,
Claudia Ma os 2, Tomás Ma ín-Pin o 2, Peñi as Ríos 5, Ne ea González-Ga cía6and JoséMa ía Acos a 3
1Nu sing School, Uni e si y o Salamanca, A . Donan es de Sang e SN, 37004 Salamanca, Spain
2Se icio de Psiquia ía, Hospi al Uni e si a io de Salamanca, 37007 Salamanca, Spain;
ubenala [email p o ec ed] (R.D.A.); [email p o ec ed] (J.M.);
[email p o ec ed] (B.C.); [email p o ec ed] (C.M.);
[email p o ec ed] (T.M.-P.)
3Ins i u o de In es igación Biomédica de Salamanca (IBSAL), Paseo de San Vicen e SN, 37007 Salamanca,
Spain; [email p o ec ed]
4Cen o de Salud Xà i a, Xà i a, 46800 Valencia, Spain; [email p o ec ed]
5Hospi al Uni e si a io Cáce es, 10004 Cáce es, Spain; [email p o ec ed]
6S a is ical Depa men , Uni e si y o Salamanca, 37004 Salamanca, Spain; ne ea_gonzalez_ga [email p o ec ed]
*Co espondence: [email p o ec ed]; Tel.: +34-639-754-620
Abs ac : T ea men -eme gen sexual dys unc ion (TESD) is one o he mos equen and pe sis en
ad e se e ec s o an idep essan medica ion. Sexual dys unc ion (SD) seconda y o SSRIs occu s
in >60% o sexually ac i e pa ien s and >80% o heal hy olun ee s, wi h his causing ea men
discon inua ion in >35% o pa ien s. Howe e , his ac o is a ely add essed in ou ine examina ions,
and only 15–30% o hese e en s a e spon aneously epo ed. A s a egy o swi ching o a di e en
non-se o one gic an idep essan could in ol e a isk o elapse o clinical wo sening due o a lack
o se o one gic ac i i y. Vo ioxe ine appea s o ha e less impac on sexual unc ion due o i s
mul imodal mechanism o ac ion. No s udies ha e been published on he e ec i eness o swi ching
o o ioxe ine in pa ien s wi h poo ly ole a ed long- e m an idep essan - ela ed SD in na u alis ic
se ings. S udy objec i es: To de e mine he e ec i eness o swi ching o o ioxe ine due o SD in
a ou ine clinical p ac ice se ing. Me hodology: obse a ional p agma ic and na u alis ic s udy o
de e mine he e ec i eness o he swi ch o o ioxe ine (mean dosage 13.11
±
4.03) in 74 pa ien s
aged 43.1
±
12.65 (54% males) a isk o discon inuing ea men due o sexual dys unc ion. The
PRSexDQ*- SALSEX scale (*Psycho opic-Rela ed Sexual Dys unc ion Ques ionnai e) was applied a
wo momen s: baseline isi and a e 3 mon hs o ollow-up. Resul s: global Sexual Dys unc ion (SD)
measu ed wi h he SALSEX scale dec eased signi ican ly be ween he baseline isi (10.32; SD 2.73)
and he ollow-up isi (3.78; SD 3.68), p< 0.001. The e was a signi ican imp o emen (p< 0.001)
a he endpoin including dec eased libido, delay o o gasm, ano gasmia and a ousal di icul ies in
bo h sexes. A e swi ching o o ioxe ine, 83.81% o pa ien s expe ienced an imp o emen in sexual
unc ion (43.2% el g ea ly imp o ed). Mos pa ien s (83.3%) who swi ched o o ioxe ine con inued
ea men a e he ollow-up isi . A o al o 58.1% o pa ien s showed an imp o emen in dep essi e
symp oms om he baseline isi . Conclusion: swi ching o o ioxe ine is an e ec i e and eliable
s a egy o ea pa ien s wi h poo ly ole a ed p e ious an idep essan - ela ed sexual dys unc ion in
eal-li e clinical se ings.
Keywo ds: sexual dys unc ion; an idep essan ; o ioxe ine; dep ession; sexuali y
1. In oduc ion
An idep essan s a e equen ly associa ed wi h sexual dys unc ion (SD), pa icula ly
SSRI se o one gic agen s, dual-ac ion d ugs, and clomip amine [
1
]. O he d ugs wi h
J. Clin. Med. 2024,13, 546. h ps://doi.o g/10.3390/jcm13020546 h ps://www.mdpi.com/jou nal/jcm
J. Clin. Med. 2024,13, 546 2 o 17
di e en mechanisms o ac ion appea o cause ewe sexual ad e se e ec s (mi azapine,
bup opion, moclobemide). Un o una ely, he eal incidence o SD is unde es ima ed, and
speci ic ques ionnai es mus be used. Spon aneous epo ing o his ad e se e ec is a ound
15–20%, while eal igu es exceed 60–80% [
2
,
3
]. The p oblem is signi ican and i is closely
associa ed wi h ea men d opou , pa icula ly in he case o long- e m ea men s, and
has a nega i e impac on he quali y o li e o pa ien s and hei pa ne s [4].
Vo ioxe ine (VOR) seems o ha e a be e p o ile in e ms o SD, al hough mos da a
comes om clinical ials wi h egis a ion pu poses ha may ha e some me hodological
limi a ions, such as he dep essi e popula ion examined and sho - e m da a [
5
]. SD a es
a y be ween 0.9% and 45%, depending on he s udy me hodology. Since he se o one gic
mechanism o ac ion seems o be closely linked wi h he e iology and pa hogenesis o
dep ession [
6
], d ugs inc easing se o onin a ailabili y a e gene ally associa ed wi h high
a es o SD, as his neu o ansmi e is e y closely in ol ed wi h inhibi ion o sexual
unc ion, impulsi i y, and appe i e, among o he s.
The physiopa hogenic mechanisms o hese phenomena appea o be mul i ac o ial
and complex [
7
]. One mechanism is he inc ease in ci cula ing se o onin and he ac i a ion
o se o onin 5-HT2A ecep o s, which could a ec o gasmic unc ion and sexual in e es .
E ec ile dys unc ion appea s o be caused by changes in ni ic oxide unc ioning and
ac i a ion o pe iphe al ad ene gic ecep o s.
Managemen o SD has been a emp ed using a ious app oaches [
8
]: wai ing o
spon aneous emission, dose educ ion, o swi ching o ano he d ug wi h a lowe p o ile
o impac on sexual unc ioning, o use o “an ido es” such as sildena il o o he simila
compounds [
4
,
9
]. Gi en he high a es o sexual dys unc ion nowadays, which a e usually
le unadd essed by clinicians, and i s impac on pa ien s’ quali y o li e and ea men
discon inua ion (es ima ed a o e 35%), his p oblem mus be di ec ly in es iga ed in all
pa ien s who ecei e an idep essan s.
In he las 10 yea s, a e y signi ican inc ease has been obse ed in he numbe o
publica ions add essing his opic, and ising a es o SD ha e been de ec ed wi h he use o
speci ic ques ionnai es [
10
–
12
], compa ed o he ini ial es ima es ob ained om spon aneous
pa ien epo s. Ini ial da a on he incidence o SD ob ained e ospec i ely anged widely:
be ween 5% and 75% depending on he s udy me hodology used. In p e ious s udies
using he alida ed ques ionnai e Psycho opic-Rela ed Sexual Dys unc ion Ques ionnai e
(PRSexDQ-SALSEX) [
10
], he mean incidence o SD wi h SSRIs and dual-ac ion agen s was
62.9–80% among sexually ac i e pa ien s [
3
,
13
]. Ne e heless, only 14–40% o hese pa ien s
spon aneously epo ed any dys unc ion in ei he males o emales. Women li ing wi h
psychia ic illness conside sexuali y o be an impo an pa o hei quali y o li e [14].
An Ame ican g oup led by Ani a Clay on (Uni e si y o Vi ginia) also used a speci ic
ques ionnai e, he Changes in Sexual Func ion Ques ionnai e (CSFQ) [
12
]. A e sc eening
a popula ion sample wi h inclusion and exclusion c i e ia, hei esul s we e simila o he
Spanish se ies, and con ibu ed da a on he low p e alence o bup opion-associa ed SD,
which was shown o be lowe han 10% [
15
]. Su p isingly, epo s om medical eco ds o
se o one gic an idep essan use ob ained h ough he esul s o egis a ion clinical ials
e e o a e y low incidence o SD (2–16%) [
16
]. These di e ences in incidence compa ed o
hose ob ained in eal clinical p ac ice a e due o he lack o use o speci ic ques ionnai es o
measu e sexual dys unc ion and a e based on spon aneous communica ion om pa ien s.
The PRSexDQ-SALSEX ques ionnai e analyzes he ollowing a iables on a scale
o se e i y o equency: (1) lowe libido; (2) delayed o gasm/ejacula ion; (3) absen o -
gasm/ejacula ion; (4) e ec ile/ aginal lub ica ion dys unc ion; and (5) pa ien ’s ole abili y
o sexual dys unc ion and isk o discon inuing ea men . The au ho and he wo king
g oup ha e published nume ous s udies ha use his me hod o e alua e equency o
SD, isk o discon inua ion, impac on quali y o li e, s udies in heal hy olun ee s, clinical
managemen p ocedu es, and global e iew s udies, such as ha in Wo ld Psychia y
2018 [4].
J. Clin. Med. 2024,13, 546 3 o 17
The ques ionnai e has been ansla ed in o mul iple languages, including F ench,
English, I alian, Ge man, Po uguese, G eek, Swedish, Finnish, Polish, and Japanese, and
has ecen ly also been alida ed in Manda in Chinese.
Al hough SD is a common side e ec o all SSRIs and dual-ac ion d ugs, he highes
a es ha e been epo ed wi h pa oxe ine o se e al easons: i s powe ul se o one gic
ac ion, i s e ec on inc easing p olac in and inhibi ing ni ic oxide, and i s g ea e an icholin-
e gic e ec . The mos common p oblems a e educed desi e and delay in achie ing o gasm.
E ec ile dys unc ion is less common, al hough a es associa ed wi h pa oxe ine, ci alop am,
and enla axine a s anda d he apeu ic doses we e a ound 30–40%. Absen o gasm o
ejacula ion is clea ly he mos poo ly ole a ed side e ec in pa ien s o bo h gende s.
In con as , he a es o SD caused by mi azapine, bup opion, and agomela ine
a e lowe han hose o SSRIs [
1
], due o hei di e en mechanisms o ac ion: mi aza-
pine blocks pos synap ic 5-HT2 ecep o s ( he s imula ion o which has been closely
ela ed wi h he de elopmen o ejacula ion and o gasm changes); bup opion has a
dopamine gic/ad ene gic ac ion; and agomela ine is a mela onin ecep o agonis and
HT2C an agonis .
The e appea o be di e ences be ween gende s. Males o e 40 yea s o age gene ally
ole a e SD wo se han emales [
3
], bu his is no obse ed in younge indi iduals, and a
leas one hi d o pa ien s conside ed discon inuing ea men o his eason. In con as ,
o he pa ien s, such as hose wi h p ema u e ejacula ion, accep ed hei SD well: he delay
in achie ing ejacula ion expe ienced a e s a ing an idep essan ea men “no malized”
hei ejacula o y ime. Su eys conduc ed in la ge pa ien se ies epo discon inua ion
igu es be ween 41.7% and 50.8% [14].
In clinical p ac ice, doc o s a e o en unawa e and unable o manage he appea ance
o hese side e ec s. This app oach would a oid he possibili y o pa ien s discon inuing
ea men , pa icula ly among hose who equi e i in he long e m.
Wi h ega ds o clinical managemen , he ea men o SD caused by an idep essan s
has no been examined using con olled and ex ensi e s udies. Scan da a a e a ailable
o guide clinicians on he mos app op ia e choice in each case, and no con olled clinical
ials ha e been pe o med in his a ea.
In he ELIXIR s udy [
17
] clinicians we e asked abou hei ea men choice in cases
o SD due o an idep essan s. The esul s indica ed ha mos psychia is s op ed o no
in e en ion, and p e e ed o wai o spon aneous emission, and a small pe cen age
chose o swi ch ea men o o add an an ido e. In Spain, [
3
] a clinical s udy wi h mo e
han 2000 pa ien s ound a a e o SD o o e 80% in pa ien s who we e ecei ing SSRIs
o dual-ac ion agen s. Spanish doc o s op ed o wai o spon aneous emission in 25%
o cases o swi ched o bup opion o agomela ine in 30% o cases. Resul s we e be e o
agomela ine (80% educ ion in SALSEX sco es) [
18
,
19
]. The use o PDE5 inhibi o s such as
sildena il, o weekend d ug holidays, was e y a e.
The main objec i e o his s udy is o analyze whe he swi ching o ano he an ide-
p essan wi h a di e en mechanism o ac ion is use ul in clinical p ac ice, educing he
equency o sexual dys unc ion and main aining an idep essan e icacy a e swi ching.
The expe ience in ou coun y shows ha while pa ien s wi h a leas 3 mon hs ollowing
can bene i om swi ching o o he non-se o one gic an idep essan s in o de o imp o e
SD, hey can be a isk o clinical de e io a ion o dep essi e elapses in one in h ee cases.
The e o e, new he apeu ic al e na i es mus be ound. In he absence o me a-analyses
and speci ically designed clinical ials, he ecommenda ions ob ained om analyzed da a
om published s udies sugges di e en le els o e idence including swi ching o ano he
an idep essan (agomela ine, bup opion o mi azapine), weekend d ug holidays (use ul in
he absence o o gasm), and PD5Inhibi o s, among o he s.
Due o he lack o an e ec i e ea men wi h a o able, pe sis en esul s in an ide-
p essan ea men -eme gen SD, newe p oduc s wi h di e en mechanisms o ac ion ha
could ha e less e ec on sexual unc ioning mus be explo ed. One o hem is o ioxe ine,
which has a mul imodal mechanism o ac ion on di e en ecep o s, wi h ull agonis e ec
J. Clin. Med. 2024,13, 546 4 o 17
on 5-HT1A, pa ial an agonism on 5-HT1B, and an agonis e ec s on 5HT1D, 5-HT3 and
5-HT7, in addi ion o displaying dopamine gic, ad ene gic, his amine gic, and choline gic
e ec s. Gi en he lack o cu en e idence ega ding his opic, speci ic s udies in ou-
ine clinical p ac ice and in ca e ully selec ed popula ions a e equi ed o con i m hese
p elimina y da a.
2. S udy Ra ionale
Vo ioxe ine is a ecen ly de eloped an idep essan wi h a no el mechanism o ac ion.
Da a om clinical ials o egis a ion pu poses sugges a neu al, o e en bene icial,
e ec on sexual unc ioning in dep essi e pa ien s ecei ing o ioxe ine [
20
,
21
], which has
since been p o ed again in a ecen phase IV andomized s udy [
22
]. A swi ching s udy
showed ha o ioxe ine is a sa e and e ec i e swi ch he apy o ea ing SSRI-induced
sexual dys unc ion in adul s wi h well- ea ed MDD [
23
]. Also, imp o emen in sexual
dys unc ion wi h o ioxe ine o esci alop am may be in luenced by p io SSRI usage, sex,
age (
≤
45 yea s, women), and his o y o one o h ee majo dep essi e episodes [
24
]. Fo
example, a ecen s udy in pos menopausal ansi ion women obse ed less an idep essan -
induced SD wi h o ioxe ine when compa ed o pa oxe ine [
25
], al hough he exac dose
was no speci ied. Howe e , o e all limi ed da a ha e been published o da e ega ding
he e ec s o his an idep essan on sexual unc ioning.
Vo ioxe ine, wi h his no el mechanism o ac ion, could ha e some implica ions
o less sexual dys unc ion. In a ecen andomized, double-blind ial wi h o ioxe-
ine (15–20 mg/day), ea men -eme gen sexual dys unc ion symp oms we e no signi i-
can ly di e en e sus placebo using he ASEX Scale [
26
]. In an open-label, lexible-dose
(2.5–10 mg/day),
52-week ex ension s udy ha e alua ed he long- e m sa e y and ole a-
bili y o o ioxe ine, he a e o ad e se e en s ela ed o sexual dys unc ion was low [
27
].
Mo eo e , a ecen p ospec i e epidemiological s udy shows ha emales (bu no males)
ea ed wi h o ioxe ine p esen ed be e sexual unc ion han hose ea ed wi h SSRIs o
Duals and a lowe isk o sexual dys unc ion [28].
In a ecen e iew [
29
], au ho s s a ed ha o ioxe ine is well ole a ed, bu is as-
socia ed wi h signi ican ly inc eased sexual dys unc ion a a dosage o 20 mg; howe e ,
o ioxe ine was shown o imp o e p e ious- ea men -eme gen sexual dys unc ion in
pa ien s wi h well- ea ed MDD o a g ea e deg ee han esci alop am. These s udies show
some limi a ions when s udying his opic, such as lack o a con ol g oup wi h sexually
ac i e pa ien s in a na u alis ic se ing, so u he speci ic s udies a e needed.
The e o e, he aim o his s udy is o de e mine he equency and in ensi y o sexual
dys unc ion (SD) a e swi ching o o ioxe ine om ano he an idep essan due o TESD.
3. S udy Objec i es
3.1. P ima y Objec i e
•
To analyze he e ec i eness o he an idep essan swi ch s a egy o o ioxe ine o he
imp o emen o sexual dys unc ion (measu ed as o al SALSEX sco e) a e 3 mon hs
o ollow-up in pa ien s wi h poo ole ance o isk o ea men discon inua ion ( he
isk o discon inua ion is de ined as a sco e ≥2 in i em 5 o he SALSEX).
3.2. Seconda y Objec i es
□
To s udy he indi idual ole ance and isk o ea men discon inua ion using he
PSRSexDQ-SALSEX ques ionnai e a baseline and o he endpoin .
□
To de e mine di e ences in SD be ween males and emales a baseline and o
he endpoin .
□
To de e mine di e ences in SD be ween di e en age g oups a baseline and o
he endpoin .
□
To de e mine di e ences in SD be ween di e en le els o se e i y o dep ession a
baseline and o he endpoin .
□
To de e mine di e ences in SD be ween di e en dosages o o ioxe ine (10–20 mg).
J. Clin. Med. 2024,13, 546 5 o 17
4. Me hodology
4.1. Design
This is a na u alis ic, p ospec i e, p agma ic, open-label, one-g oup s udy design in a
ou ine clinical p ac ice se ing, measu ing he ou comes o an idep essan swi ching o
o ioxe ine in pa ien s wi h p e ious an idep essan - ela ed poo ly ole a ed SD.
4.2. S udy Subjec s
4.2.1. Sample Size Calcula ion
To analyze he e ec i eness o he an idep essan swi ch s a egy o o ioxe ine o
he imp o emen o sexual dys unc ion, and conside ing he equency o SD o di e en
an idep essan s in p e ious s udies, he sample size necessa y o he di e ence be ween
p opo ions was calcula ed. Assuming a 95% con idence le el and a powe o 80%, acco d-
ing o da a om p e ious s udies in which he p opo ion o pa ien s wi h SD on SSRIs
was 70% and 45% on dual-ac ion d ugs [
2
,
3
], and based on ecen s udies wi h he same
design, he equi ed sample size is 124 pa ien s, wi h a sample size o 62 male and 62 emale
pa ien s in each g oup in o de o obse e possible gende di e ences.
4.2.2. Inclusion C i e ia
□
Pa ien s who showed a leas mode a e in ensi y in hei o al SALSEX sco e, wi h a
sco e ≥6 (including ≥2 in i em 5, ole ance o sexual dys unc ion).
□
Pa ien s wi h no mal sexual unc ion p io o aking an idep essan s (no mal sexual
unc ion was de ined as an absence o habi ual dys unc ions o su icien in ensi y
o cause subjec i e discom o in he pa ien in he a eas o desi e, o gasm o sexual
a ousal ha would equi e specialized a en ion, wi h p e ious egula , sa is ac o y
sexual and/o au oe o ic p ac ices).
□
Sexually ac i e pa ien s ea ed wi h an an idep essan o a leas 2 mon hs. This ime
equi emen was included o a oid alse nega i es, as some symp oms do no appea
un il a e his pe iod (loss o sexual desi e o e ec ile/ aginal
lub ica ion dys unc ion).
□
P e ious an idep essan - ela ed sexual dys unc ion. Pa ien s we e swi ched o o -
ioxe ine only i he e we e symp oms o sexual dys unc ion ha we e conside ed
associa ed wi h he p e ious an idep essan .
□
T ea men exclusi ely wi h an idep essan s used wi hin app o ed label (including
SSRIs, SNRIs). Combined ea men wi h benzodiazepines a low clinical doses was
pe mi ed (less han 20 mg clo azepa e o equi alen ).
□
Pa ien s wi h a leas pa ial esponse wi h a maximum sco e on he Clinical Global
Imp ession Scale o Dep ession (CGI-D) ≤3-mild dep ession.
4.2.3. Exclusion C i e ia
□
SD p io o s a ing adminis a ion o he an idep essan . (Only a mild dec ease in
libido be o e s a ing an idep essan ea men was pe mi ed, as his is conside ed a
symp om o dep ession i sel , al hough wo sening o libido because o ea men was
conside ed as an ad e se e ec .)
□Combina ion o he an idep essan wi h an ipsycho ic d ugs o mood s abilize s.
□
Use o ho mones o any o he medica ion wi h known capaci y o in e e e in sexual e-
la ionships (an iepilep ic d ugs, H2 an agonis s, ecen in oduc ion o con acep i es
as concomi an he apy, β-blocke s, opia es, and an ihype ensi e d ugs).
□Medically signi ican in e cu en diseases clea ly a ec ing sexual unc ion.
4.2.4. Swi ching P ocedu es
Swi ching om p e ious an idep essan he apy (SSRI, SNRI) was unde aken wi h
no ab up in e up ions. Doses we e inc eased up o 10 mg/day du ing he i s week and,
ollowing a na u alis ic design, an inc ease up o 15–20 mg/day o o ioxe ine was allowed
a e he i s week. P e ious an idep essan s we e simul aneously g adually ape ed down
by hal ing he dose o he i s week be o e comple e wi hd awal.

J. Clin. Med. 2024,13, 546 6 o 17
4.2.5. Si es
All pa ien s we e a ended by psychia is s wo king in Salamanca’s (Spain) comple e
ou pa ien ne wo k, which comp ises i e ou pa ien uni s in o al.
4.3. Va iables
4.3.1. P ima y Va iable
□
The Se e i y o global SD was measu ed using he SALSEX o al sco e (sco ing om
0 = no
sexual dys unc ion o 15 = maximum sexual dys unc ion) a baseline and o he
endpoin . The se e i y o each indi idual dimension o sexual unc ioning ( educed
sexual desi e, delay o o gasm, ano gasmia, and a ousal di icul ies such as e ec ile
dys unc ion o aginal lub ica ion) was measu ed wi h a Like scale (0 = no SD;
3 = maximum SD
) o he i ems 1–4 o he SALSEX ques ionnai e a baseline and a
endpoin isi .
4.3.2. Seconda y Va iables
□
To s udy he indi idual accep ance o SD and isk o ea men discon inua ion, we
used he sco e o i em 5 o he SALSEX ques ionnai e (0 = no isk o discon inua ion;
3 = maximum isk) a baseline and a endpoin isi .
□To de e mine di e ences in SD ha a ied ac oss he se e i y o dep ession we used
he Clinical Global Imp ession-Imp o emen (CGI-I) scale o dep ession, and he
CGI-S o sexual unc ioning a baseline and a endpoin isi .
4.4. Da a Collec ion and Analysis
4.4.1. Measu emen Scales
PRSexDQ-SALSEX Ques ionnai e
The SALSEX ques ionnai e o he E alua ion o Psycho opic-Rela ed Sexual Dys unc-
ion was used o measu e and e alua e he p e alence and se e i y o SD ( alida ed in 2008
by Mon ejo e al. [
10
] in a popula ion wi h dep essi e diso de s). This ques ionnai e was
adminis e ed a baseline and du ing he ollow-up pe iod (wi hin 3 mon hs o he ini ial
isi ). I is included in an annex a he end o his pape . The SALSEX ques ionnai e is mean
o be adminis e ed du ing a di ec clinical in e iew o collec in o ma ion on whe he
ea men - ela ed SD is de ec ed, and i i is p esen , o no e whe he he pa ien epo ed
he SD spon aneously o no . The deg ee o SD is e alua ed acco ding o 4 i ems, o each o
he possible mani es a ions o SD: (1) sexual desi e; (2) delayed o gasm; (3) absen o gasm;
(4) e ec ion-lub ica ion. A i h i em e alua es he accep ance o SD, i p esen . Each o
hese i ems is sco ed be ween 0 (no p oblem) and 3 (maximum in ole ance).
The p esence and se e i y o SD is e alua ed acco ding o he o al sco e and indi idual
i em sco es o he ques ionnai e, using he ollowing c i e ia:
#
No SD: To al sco e o 0 o 1, only i i em 1 is e alua ed as a sligh loss o libido (which
is equi alen o a sco e o 1 on ha i em).
#
SD p esen : To al sco e o 2–15, o o al sco e o 1 i any i em excep i em 1 (desi e) is
sco ed 1.
□
Mild SD: 1–5 poin s, p o ided no i em sco es
≥
2 poin s and i em 5 ( ole abili y)
is no >1.
□
Mode a e SD: 6–10 poin s, p o ided ha no i em sco es
≥
3 poin s, o <6 poin s
i any i em = 2 and p o ided ha i em 5 ( ole abili y) is no >2.
□
Se e e SD: 11–15 o <11 poin s i any i em = 3 o whene e i em 5 ( ole abili y) = 3.
Clinical Global Imp ession Scale, se e i y subscale, applied o sexual dys unc ion (CGI-S-
SD) o assess he DS se e i y a baseline
Clinical Global Imp ession Scale, imp o emen subscale, applied o sexual dys unc ion
(CGI-I-SD) o assess he clinical e ec i eness o he in e en ion, adminis e ed in he
ollow-up isi (pe o med wi hin 3 mon hs o he baseline isi )
J. Clin. Med. 2024,13, 546 7 o 17
Clinical Global Imp ession Scale, se e i y subscale (CGI-S), applied o he psychia ic
disease o which he an idep essan ea men is adminis e ed, o assess se e i y a baseline
Clinical Global Imp ession Scale, imp o emen subscale (CGI-I), o assess he clinical
e ec i eness o he in e en ion, adminis e ed in he ollow-up isi (pe o med wi hin 3
mon hs o he baseline isi )
Ad e se E en s Assessmen s
Ad e se e en s (including p e- ea men ad e se e en s) had o be eco ded on an
Ad e se E en Fo m. The in es iga o had o p o ide in o ma ion on he ad e se e en ,
p e e ably wi h a diagnosis, o a leas wi h signs and symp oms; s a and s op da es (and
s a and s op ime i he ad e se e en las ed less han 24 h); se e i y; causal ela ionship
o he IMP; ac ion aken; and ou come. I he ad e se e en was no ela ed o he IMP, an
al e na i e e iology had o be eco ded, i a ailable. I he ad e se e en was an o e dose,
he na u e o he o e dose had o be s a ed ( o example, medica ion e o , acciden al
o e dose, o in en ional o e dose). I he ad e se e en was se ious, his had o be indica ed
on he Ad e se E en Fo m. The sponso /in es iga o had o comply wi h all na ional
ules and egula ions conce ning he epo ing o Se ious Ad e se E en s as de ined in he
ICH GCP guidelines and o wa d a copy o any such epo s o Lundbeck, and o epo all
AE/ADRs o Lundbeck immedia ely. ICH.
4.4.2. Visi s
In o ma ion was collec ed on wo isi s:
□Baseline isi (V1): ea men ini ia ion swi ch i p omp ed by poo ly ole a ed SD;
□
Visi 2 (V2) conduc ed wi hin 3 mon hs o ollow-up a e swi ching an idep essan a
baseline isi .
4.4.3. T ea men
Pa ien s swi ched ea men s only i he clinician and/o he pa ien conside ed ha
some ea men modi ica ion was necessa y o imp o e SD due o he use o he cu en
an idep essan , which was eplaced by o ioxe ine wi h he pa ien ’s consen .
4.4.4. E hical and Legal Conside a ions
Pa ien In o ma ion
In o med consen was ob ained om he pa ien , and he physician in ol ed he
pa ien and his/he pa ne in he s udy, since hei collabo a ion was deemed essen ial.
Con iden iali y
Collec ion, p ocessing, and ans e o s udy da a we e conduc ed in compliance
wi h he p o isions o he Spanish O ganic Law 15/1999 on Pe sonal Da a P o ec ion. All
in o ma ion on he iden i y o pa icipa ing pa ien s was ea ed as con iden ial o all
pu poses. The iden i y o he pa ien s was no o be disclosed o sha ed, excep when
necessa y o hei ea men , e alua ion, ollow-up, and sa e y. The pa ien was iden i ied
in he da a collec ion o ms wi h a pa ien numbe . The collec ed da a we e en e ed in a
da abase ollowing a p ocedu e ha ensu ed o al dissocia ion be ween hese da a and he
iden i y o he pa ien .
5. Da a Analysis
5.1. E alua ion C i e ia and Da a Managemen
Case epo o ms (CRFs) we e indi idually e iewed o ensu e ha all da a had been
collec ed o o he wise a eason had been p o ided. Nume ical alues we e assigned o he
open ex ields, pa icula ly o ad e se eac ions. Inco ec and incomple e CRFs, and
hose ha had no been comple ed acco ding o he p o ocol we e ejec ed o e u ned o
he co esponding in es iga o o e iew and co ec ion.
J. Clin. Med. 2024,13, 546 8 o 17
CRF da a conside ed alid was en e ed in a da abase c ea ed o his pu pose wi h
app op ia e sa e y measu es and in e nal cohe ence ules, a e which any cases wi h
anomalous o inconsis en alues we e e iewed.
5.2. E alua ion C i e ia
Cases ejec ed due o se ious inconsis encies o inco ec o incomple e da a we e
no e alua ed. All pa ien s we e o be desc ibed in he pa icipan ’s biodemog aphic
cha ac e is ics sec ion, indica ing he o al numbe o pa ien s included, he o al numbe o
pa ien s excluded o who had discon inued ea men ea ly (along wi h he eason), and
he o al numbe o e aluable pa ien s. Pha maco igilance assessmen was based on all
ec ui ed pa ien s, excep o hose cases ejec ed due o inco ec da a o hose who did no
e u n o any isi a e baseline.
E alua ions Pe o med
Gene al cha ac e is ics o pa ien s included in he s udy, including biodemog aphic
da a and hei psychia ic diagnosis, we e desc ibed. The p ima y analysis was con-duc ed
by desc ibing he pe cen age o pa ien s who had SD du ing p e ious ea men and a e
swi ching o o ioxe ine wi h hei espec i e con idence in e als. To al SALSEX sco e,
equency, and in ensi y o each i em o he SALSEX (i ems 1–5) was compa ed a endpoin
s. baseline.
Tes ing o he hypo hesis was conside ed signi ican when he co esponding p- alue
was less han 5% (
α
= 0.05) o wo- ailed es s. All ope a ions we e pe o med on PC- ype
compa ible compu e s, p o ec ed by s ic measu es con olling access and quali y, using
he SPSS package, e sion 23.0 o Windows o a subsequen e sion.
Measu es o cen al endency and dispe sion o quan i a i e a iables we e de-
e mined h oughou he s udy. No mali y o dis ibu ion o con inuous a iables was
es ed using he Kolmogo o -Smi no es o one sample, so ha he da a we e sub-
sequen ly analyzed based on he esul s ob ained. The desc ip i e analysis included
ca ego ical quali a i e a iables measu ed using equencies and pe cen ages.
Fo he in e en ial s a is ical analysis, es ing o he hypo hesis was e alua ed using
he app op ia e pa ame ic es o a iables wi h no mal dis ibu ion, o non-pa ame ic
es s o hose wi h non-no mal dis ibu ion. Th oughou he s udy, i was o in e es o
examine di e ences be ween he pa ien g oups in he cha ac e is ics e alua ed. When
expe imen al da a we e measu ed using con inuous scales ha ollow a no mal dis i-
bu ion, he app op ia e p ocedu e was he S uden ’s es o wo independen samples. I
hese scales did no ha e a no mal dis ibu ion, a non-pa ame ic Mann–Whi ney U es
was used. I he di e ence o means was o be s udied be ween mo e han wo g oups, he
co esponding pa ame ic o non-pa ame ic es was used.
Pea son’s chi-squa ed es o independence and Fishe ’s exac es we e used o
compa e independence be ween ca ego ical a iables.
6. P ojec De elopmen S ages
The s udy was conduc ed in he Depa men o Psychia y o he Hospi al Uni e -
si a io de Salamanca, wi h he pa icipa ion o 10 in es iga o s om 5 men al heal h
ou pa ien uni s loca ed in Salamanca, which p o ides ca e o a popula ion close o
300,000 inhabi an s.
The s udy was pe o med in h ee phases be ween July 2019 and Sep embe 2022.
Rec ui men was delayed due o COVID-19.
All adminis a i e pe missions, including submission o he p o ocol o quali ica ion
by he Spanish Agency o Medicines, ag eemen om he Resea ch E hics Commi ee o
he Salamanca Heal h A ea, and ag eemen om he Go e nmen o Cas ile and Leon we e
ob ained in 2019. An in es iga o s’ mee ing was held in Janua y 2020 o an explana ion o
he p o ocol, s anda diza ion o p ocedu es, aining, and p ac ical adminis a ion o he
SALSEX ques ionnai e o educe in e -in es iga o a iabili y. The collec ion o baseline
J. Clin. Med. 2024,13, 546 9 o 17
sociodemog aphic da a was ob ained and included in he CRF, as well as all selec ion
c i e ia, p esence and se e i y o he psychia ic disease (measu ed using he CGI-S scale),
p esence and se e i y o SD (measu ed wi h he SALSEX ques ionnai e and he CGI-S-SD),
and andomized he apeu ic s a egy o an idep essan swi ch o he managemen o SD
associa ed wi h an idep essan ea men .
Clinical ollow-up o pa ien s wi h SD de ec ed a he baseline isi included he
measu emen , wi hin 3 mon hs o baseline, o he e ec i eness o he in e en ion using
he SALSEX scale (lowe sco es indica e imp o emen ), and a Clinical Global Imp ession-
Imp o emen o dep ession (CGI-IDep) and o sexual unc ioning (CGI-ISex) a e in e -
en ion. A de e mina ion o he numbe o pa ien s wi hd awing om he s udy due o
lack o e icacy, ad e se e ec s o loss o ollow-up was pe o med.
7. Resul s
103 pa ien s ea ed wi h an an idep essan who had poo ly ole a ed sexual dys unc-
ion a e ini ia ion o ea men and who me he inclusion and exclusion c i e ia o he
p o ocol we e swi ched o o ioxe ine. The esponse o he SALSEX scale was analyzed
in 74 pa ien s om whom da a we e ob ained a he ollow-up isi (3 mon hs a e he
baseline). 29 ou o 103 pa ien s (28.15%) we e los o he s udy wi h no da a a Visi
2. Clinical and sociodemog aphic cha ac e is ics o pa ien s swi ched o o ioxe ine a e
showed in Table 1.
Table 1. Clinical and sociodemog aphic cha ac e is ics o pa ien s swi ched o o ioxe ine.
n= 74
Age (yea s) 43.1 ±12.65
<30, n(%) 14 (18.9)
30–40, n(%) 21 (28.4)
40–50, n(%) 17 (23.0)
>50, n(%) 22 (29.7)
Gende (Males), n(%) 40 (54.1)
Gende (Females), n(%) 34 (45.9)
Du a ion o ea men (mon hs) (Baseline) 19.53 ±37.27
Du a ion o ea men (mon hs) (Follow-up) 3.21 ±1.17
Dosage (mg/d) (Follow-up) 13.11±4.03
SALSEX To al Sco e a Baseline 10.32 ±2.73
SALSEX To al Sco e a Follow-up 3.78 ±3.68
7.1. P e ious An idep essan T ea men a Baseline
A baseline, pa ien s wi h sexual dys unc ion we e aking enla axine 6.8%, mean
dosage 177 mg/day
±
73.02; esci alop am 25.7%, 14.74 mg/day
±
3.90; ci alop am
5.4%, 23.75 mg/day
±
7.50; pa oxe ine 9.5%, 22.86 mg/day
±
7.56; se aline 18.9%,
78.57 mg/day ±37.80;
luoxe ine 8%, 23.33 mg/day
±
8.17; duloxe ine 10.8%,
67.50 mg/day ±21.21;
clomip amine 4.1%, 75.00 mg/day
±
0.000 and des enla axine
10.8%, 78.57 mg/day ±56.70 (Figu e 1).
7.2. SALSEX Scale To al Sco e o Sexual Dys unc ion
The o al sco e o Sexual Dys unc ion (SD) measu ed wi h he SALSEX scale ( anging
om 0 = no sexual dys unc ion o 15 = s ong SD) a he baseline isi in which pa ien s
we e aking an an idep essan was 10.32 (SD 2.73). The o al sco e on he SALSEX scale in
he ollow-up isi (3 mon hs a e swi ching o o ioxe ine) was 3.78 (SD 3.68). Highly
signi ican di e ences we e ound be ween he global SALSEX sco e a baseline and a e
swi ching o o ioxe ine ( = 12.279, p< 0.001).
A baseline, 4% o pa ien s had mild sexual dys unc ion (SD) (n= 3), 20.3% o pa ien s
had mode a e SD (n= 15) and 75.7% o pa ien s had se e e SD (n= 56).
SD was spon aneously epo ed in 47.3% o pa ien s (n= 35), compa ed o 52.7%
(n= 39) o whom i was no .
J. Clin. Med. 2024,13, 546 16 o 17
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