Antidepressant-Induced Sexual Dysfunction
among Newer Antidepressants in a Naturalistic Setting
ObjectiveaaAntidepressants used to treat depression are frequently associated with sexual
dysfunction. Sexual side effects affect the patient’s quality of life and, in long-term treatment,
can lead to non-compliance and relapse. However, studies covering many antidepressants
with differing mechanisms of action were scarce. The present study assessed and compared
the incidence of sexual dysfunction among different antidepressants in a naturalistic setting.
MethodsaaParticipants were married patients diagnosed with depression, per DSM-IV diag-
nostic criteria, who had been taking antidepressants for more than 1 month. We assessed the par-
ticipants via the Arizona Sexual Experiences Scale (ASEX), Beck Depression Inventory (BDI),
and State-Trait Anxiety Inventory (STAI), and assessed their demographic variables, types
and dosages of antidepressants, and duration of antidepressant use via their medical records.
ResultsaaOne hundred and one patients (46 male, 55 female, age 42.2±7 years) completed
the instruments. Thirteen were taking fluoxetine (mean dose 21.3±8.5 mg/day), 24 were tak-
ing paroxetine (mean dose 20.4±7.2 mg/day), 20 taking citalopram (mean dose 22.1±6.5 mg/day),
22, venlafaxine (mean dose 115.7±53.2 mg/day) and 22, mirtazapine (mean dose 18±8.7 mg/day).
Mean ages, sex ratios, and BDI and STAI scores did not differ significantly across antidepres-
sants. A substantial number of participants (46.5%, n=47) experienced sexual dysfunction. The
prevalence of sexual dysfunction differed across drugs: citalopram 60% (n=12), venlafaxine 54.5%
(n=12), paroxetine 54.2% (n=13), fluoxetine 46.2% (n=6), and mirtazapine 18.2% (n=4). Regres-
sion analyses revealed the significant factors for sexual dysfunction were being female, total scores
on the BDI and SAI, and type of antidepressant (F=4.92, p<0.0001). Of the antidepressants, the
mirtarzapine group’s total ASEX score was significantly lower than the scores of the citalopram,
fluoxetine, and paroxetine groups.
ConclusionaaThe incidence of sexual dysfunction was substantially high during antidepres-
sant treatment. The incidence of sexual dysfunction differed among antidepressants having dif-
ferent mechanisms of action. Our study suggests the need for clinicians to consider the impact of
pharmacotherapy on patients’ sexual functioning in the course of treatment with antidepressants.
Psychiatry Investig 2010;7:55-59
Key Wordsaa Depression, Sexual dysfunction, Antidepressants.
Received: July 20, 2009 Revised: October 16, 2009 Accepted: November 17, 2009
Available online: February 8, 2010
Young Min Lee2
Chung Tai Lee1
1 Department of Psychiatry,
College of Medicine,
The Catholic University of Korea,
2 Department of Psychiatry,
School of Medicine,
Pusan National University,
Yong-Sil Kweon, MD, PhD
Department of Psychiatry,
College of Medicine,
The Catholic University of Korea,
Uijeongbu 480-130, Korea
cc This is an Open Access article distributed
under the terms of the Creative Commons At-
tribution Non-Commercial License (http://cre-
permits unrestricted non-commercial use, dis-
tribution, and reproduction in any medium, pro-
vided the original work is properly cited.
Print ISSN 1738-3684 / On-line ISSN 1976-3026
Copyright © 2010 Korean Neuropsychiatric Association 55
With regard to side effects, numerous clinical needs remain persistently unmet, despite the
advances of psychopharmacology. Antidepressant therapy, although effective for treating the
symptoms of depression, frequently induces or exacerbates the relatively common side effect
of sexual dysfunction,1-5 which occurs in approximately one-half of patients. During antide-
pressant treatment, typical sexual dysfunction symptoms include diminished or absent libi-
do, arousal difficulties, erectile dysfunction (in men), vaginal lubrication difficulties (in wom-
en), delayed orgasm, and anorgasmia. These sexual side effects may affect the patient’s quality
of life and can lead to non-compliance and relapse in long-term treatment.6
Of the newer antidepressants, venlafaxine, mirtazapine, and the selective serotonin reup-
56 Psychiatry Investig 2010;7:55-59
Sexual Dysfunction in Newer Antidepressants
take inhibitors (SSRIs) constitute the most commonly presc-
ribed drugs. The incidence of sexual dysfunction seems to dif-
fer among these antidepressants as a result of their differ-
ences in mechanism of action. Although the SSRIs have a
more favorable side-effect profile than do the tricyclic antide-
pressants, sexual dysfunction remains a significant problem
with their use.7 A recent review suggests that between 30% and
60% of SSRI-treated patients may experience some form of
treatment-induced sexual dysfunction.8 Venlafaxine is a sero-
tonin-norepinephrine reuptake inhibitor (SNRI), differing from
the SSRIs in that it inhibits the reuptake of both serotonin and
norepinephrine. Reportedly, the rates of sexual dysfunction
with venlafaxine are lower or similar to those of SSRIs.9 Mir-
tazapine is unique in its mechanism of action, stimulating the
release of serotonin and norepinephrine. Because it blocks the
type 2 and 3 serotonin receptors, this drug theoretically pro-
duces less sexual side effects than do SSRIs.
Although many studies of antidepressant-induced sexual
dysfunction have been conducted in western societies, there
is little information on the incidence of such in Korea. Chae et
al.10 reported that patients taking mirtazapine experienced
significantly less side effects, in terms of decreased libido and
anorgasmia, than did those taking SSRIs (35.3% vs. 64.9% and
35.3% vs. 64.9%, respectively). Though Chae et al.10 used a
self-rating instrument designed to measure the subjective symp-
toms of patients, that instrument was not specific for the asse-
ssment of sexual dysfunction. The Arizona Sexual Experienc-
es Scale (ASEX)11 is a gender-specific, five-item self-report
measure that specifically assesses sexual functioning in terms
of current level of sexual drive, psychological arousal, physio-
logic arousal (erections or vaginal lubrication), ease of orgasm,
and orgasm satisfaction. Thus, in the present study, we used the
ASEX to investigate the prevalence of sexual dysfunction am-
ong depressed patients taking the newer antidepressants (cita-
lopram, fluoxetine, paroxetine, venlafaxine, and mirtazapine).
We recruited our participants from the married outpatients
of the Department of Psychiatry, Uijeongbu St. Mary’s Hospi-
tal, the Catholic University of Korea. Patients were eligible if
they 1) were between 18 and 50 years, 2) had a diagnosis of a
depressive disorder that met DSM-IV criteria, 3) had been tak-
ing SSRI (fluoxetine, paroxetine, or citalopram), venlafaxine,
or mirtazapine monotherapy for more than 1 month. We exclud-
ed patients for any one of the following reasons: diagnosis of
a sexual disorder before antidepressant treatment; uncont-
rolled psychiatric disorder, diabetes mellitus; history of stroke,
congestive heart failure, unstable cardiac condition, arrhythmia,
or myocardial infarction within the last 6 months; alcohol or
substance use disorder; current use of other therapies or medi-
cations to treat sexual dysfunction; and use of hormone therapy.
As mentioned, we assessed the participants’ sexual functi-
oning using the Arizona Sexual Experiences Scale.11 This sc-
ale has demonstrated internal consistency, having a test-retest
reliability significant at the 0.01 level. The ASEX’s sensitivity
and specificity for identifying sexual dysfunction in subjects is
82% and 90%, respectively. Subjects rate their current level
of sexual drive, psychologic arousal, physiological arousal (erec-
tions or vaginal lubrication), ease of orgasm, and orgasm satis-
faction on a 6-point Likert scale. Ratings range from extreme-
ly positive 1) to none/never 6) for each of the five items, for a to-
tal score ranging from 5 to 30. A total ASEX score of 19 or grea-
ter, any one item with an individual score of 5 or greater, or any
three items with individual scores of 4 or greater are all highly
correlated with the presence of clinician-diagnosed sexual
For this study, two psychiatrists fluent in English translated
the ASEX into Korean, and two other psychiatrists translated
this Korean version back into English. The translation and
back-translation procedure was repeated by four psychiatrists
until they agreed that back-translation was sufficiently simi-
lar to the original scale.
We divided the ASEX item scores into subscores for 1) de-
sire, 2) arousal, including sex drive and arousal, and 3) or-
gasm, including ease of orgasm and orgasm satisfaction. Then,
we averaged the subscores for arousal and orgasm, each con-
taining two items, to get a single mean score.
To control for the effect of depression and anxiety on sexu-
al functioning, we also assessed participants using the Beck
Depression Inventory (BDI)13 and State-Trait Anxiety Inven-
tory (STAI)14,15 and assessed their demographic variables,
type and dosages of antidepressants, and duration of antidepr-
essant use via their medical records.
The study’s data analysis used the t-test or chi-square statis-
tics, depending upon the type of variable being investigated.
Among the participant groups, each using a different antide-
pressant, we compared the ASEX total differences and sub-
scale scores, using ranks, by means of the Kruskal-Wallis
test and the least significant difference (LSD). We used mul-
tiple regression analysis to determine which variables related
to sexual dysfunction, considering a probability (p) value of
less than 0.05 to be significant, and employed SAS 8.01 (SAS
Institute, Cary, NC, USA) for the statistical analysis. The hospi-
tals’ institutional review boards approved this study. Each of the
participants provided informed consent for their participation
in this study after receiving a full explanation of the procedure.
One hundred and one participants (46 male, 55 female;
mean age 42.2±7) completed all instruments. Of these partici-
pants, 20 were taking citalopram (mean dose 22.1±6.5 mg/
day), 13 were taking fluoxetine (mean dose 21.3±8.5 mg/day),
KU Lee et al.
24 taking paroxetine (mean dose 20.4±7.2 mg/day), 22, venla-
faxine (mean dose 115.7±53.2 mg/day), and 22, mirtazapine
(mean dose 18±8.7 mg/day). Mean ages, sex ratios, and scores
on the BDI and STAI did not differ significantly across these
antidepressants (Table 1).
A substantial number of patients (46.5%, n=47) showed
sexual dysfunction. The prevalence of sexual dysfunction dif-
fered across the drugs: citalopram 60% (n=12), venlafaxine
54.5% (n=12), paroxetine 54.2% (n=13), fluoxetine 46.2% (n=
6), and mirtazapine 18.2% (n=4)(Figure 1). Regression analy-
ses revealed that the significant factors for sexual dysfunc-
tion were gender (being female increased the probability of sex-
ual dysfunction), total BDI score, total SAI score, and type of
antidepressant (citalopram, fluoxetine, and paroxetine increa-
sed the probability of sexual dysfunction as compared to mir-
tazapine)(F=4.92, p<0.0001). The mirtazapine group’s total
ASEX score was significantly lower than the scores of the
fluoxetine, paroxetine, and venlafaxine groups (Table 2). The
mirtazapine group’s subscore on ease of orgasm was also sig-
nificantly lower than the subscores of the paroxetine, citalo-
pram, and venlafaxine groups (p<0.005)(Table 2).
Sexual dysfunction associated with antidepressant treat-
ment is not uncommon.16 Although in many cases antidepres-
sants can improve the sexual dysfunction associated with de-
pression, the dysfunction consequent to the medications them-
selves are potentially important concerns for the patient.16
In the present study, approximately half the patients taking
antidepressants experienced sexual dysfunction. Comparison
of the prevalence of sexual dysfunction among the participants
according to the different drugs they were taking revealed re-
levant differences, as follows: citalopram 60%, fluoxetine 46.2%,
paroxetine 54.2%, venlafaxine 54.5%, and mirtazapine 18.2%.
These findings replicate the results of previous studies,
which have shown both a substantial number of patients suf-
fering from sexual dysfunction and that SSRI users experi-
ence a higher incidence of sexual dysfunction than do mirta-
The overall incidence and the type of sexual dysfunction
appear to be differentially associated among the classes of an-
tidepressants, and also, possibly, within the classes.4,18 Tricy-
clic antidepressants, SSRIs, and monoamine oxidase inhibitors
are frequently associated with sexual dysfunction. Other anti-
depressants (e.g., bupropion, moclobemide, reboxetine, mirta-
zapine, and nefazodone) seem to be associated with lower in-
cidence of sexual dysfunction than the older antidepressants.4
As a group, SSRIs, venlafaxine, and mirtazpine are among
the most commonly prescribed medications for controlling the
symptoms of depression, due to their reduced side effect pro-
files, which enhance patient compliance. Nevertheless, because
of their different mechanisms of action on the receptors, these
medication types have different impacts on sexual function-
ing. Of the newer antidepressants, SSRIs seem most likely to
cause sexual dysfunction. SSRIs act specifically on the sero-
tonin system, but they also affect other monoamines. For insta-
nce, paroxetine has D2-blocking properties, thereby affecting
the dopaminergic mesolimbic reward system.19 This can in-
crease the risk of hyperprolactinemia and sexual dysfunc-
tion.20,21 In addition, paroxetine inhibits nitric oxide synthase
activity, which is required for erection.22,23 In the study by
Montejo et al.,17 which compared all five SSRIs, paroxetine and
citalopram were associated with the highest overall prevalenc-
es of sexual dysfunction. In the present study, citalopram (60%)
and paroxetine (54.2%) tended to be associated with more fre-
Table 1. Demographic and clinical variables of patients taking various antidepressants
8 : 12
6 : 7
11 : 11
12 : 12
9 : 13
Sex (Male : Female)
Mean duration of administration (weeks)*
Mean dosage (mg/day)
State Anxiety Inventory
Trait Anxiety Inventory
Beck Depression Inventory
*p<0.05 Citalopram vs. Fluoxetine
Figure 1. Frequencies of sexual dysfunction among antidepres-
sants (χ2=9.696, p<0.05).
Citalopram FluoxetineParoxetine Venlafaxine Mirtazapine
Frequency of sexual dysfunction (%)
58 Psychiatry Investig 2010;7:55-59
Sexual Dysfunction in Newer Antidepressants
quent sexual dysfunction than fluoxetine was (46.2%), though
the difference was not statistically significant.
From the standpoint of sexual dysfunction, patients seem to
tolerate the dual action antidepressants relatively well. The
SNRIs now comprise three medications: venlafaxine, milnacip-
ran, and duloxetine. The use of venlafaxine produces some de-
gree of delayed orgasm, but the frequency of this is considerably
lower than for SSRI use.24 In the case of milnacipran, there have
been no systematic surveys. However, studies in volunteers25
have not revealed any such effects. With regard to sexual dys-
function, the difference between venlafaxine and milnacipran
may be due to the former’s relative selectivity toward serotonin
reuptake and the latter’s toward noradrenaline reuptake. Venla-
faxine at low doses only blocks serotonin reuptake, whereas at
higher doses (generally described as >150 mg/d), it is also a po-
tent norepinephrine reuptake inhibitor.26 At very high doses,
venlafaxine blocks dopamine reuptake.26 Thus, theoretically,
sexual side-effects should decrease as the venlafaxine dose in-
creases. Because this study used relatively low doses of venla-
faxine (115 mg), the sexual dysfunction frequency associated
with venlafaxine was similar to that of the SSRIs.
Studies have shown that mirtazapine is associated with a
low rate of sexual dysfunction. About 24.4% of mirtazapine-
treated patients experience any type of sexual dysfunction.17
One of the noradrenergic and specific serotonergic antidepre-
ssants (NaSSAs), mirtazapine is a presynaptic alpha2-adren-
ergic receptor antagonist, facilitating the release of norepine-
phrine and serotonin. However, mirtazapine’s 5HT2 blocking
properties reduce the potential for sexual dysfunction, partic-
ularly anorgasmia. Mirtazapine is also a potent antagonist of
postsynaptic 5-HT3 receptors, which may further promote or-
gasm. The present study, showing mirtazapine was associat-
ed with both lowest overall sexual dysfunction frequency and
greatest ease of orgasm, is in line with mirtazapine’s unique
mechanisms of action.
This study has several limitations. First, the small sample
size did not facilitate a comparison between the low-inciden-
ce adverse effects. Since response rate is generally low in sur-
veys on sensitive topics,27,28 interpretation of the findings re-
quires caution. Future studies need to use larger sample sizes.
Second, the participants were free to take medications other
than those analyzed in the study. Therefore, we cannot rule out
the possibility that the incidence of side effects might have
been influenced by other medications the participants were
taking. Third, we did not make an initial assessment of partici-
pants’ sexual dysfunction before treatment. Thus, it is difficult
to distinguish antidepressant-induced sexual dysfunction from
the participants’ remaining symptoms of depression. However,
since the participants’ severity of depression was mild (mean
BDI score was 11.9±9.0) and improved with treatment, their
sexual dysfunction may more likely be the result of medication
side effects. Fifthly, a comparison with a non-depressed control
group may provide more information about the medications’
In conclusion, this study suggests that sexual dysfunction
often occurs with antidepressants treatment and may occur at
different rates in patients treated with different medications.
Clinicians should be alert to the appearance of this undesirable
side effect in order to adopt the best strategy for managing de-
pression, thus avoiding a deterioration in the patient’s quality
of life and possible withdrawal from the treatment.
This study was supported by a grant of the Korean Health 21 R & D Pro-
ject, Ministry of Health and Welfare, Republic of Korea (A050047).
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Sexual drive 04.00±0.91
p value Multiple comparison test*
MIR<FLU, PAR, VEN
Ease of orgasm
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MIR<PAR, CIT, VEN
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