Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of commonly prescribed antidepressants in clinical practice. Sexual dysfunction is a common side effect of SSRIs, which often goes unrecognized but adversely affects the quality of life of the patient. This review takes a look at the occurrence of sexual dysfunction among patients receiving SSRIs from a clinical viewpoint. The review explores into the possible reasons of such a dysfunction and the differential diagnoses to be entertained while dealing patients receiving SSRIs and experiencing sexual dysfunction. The review discusses the management strategies for addressing such dysfunction due to SSRIs, including cessation or reduction of dose, changing to another antidepressant, augmentation with another antidepressant, additional use of medications for erectile dysfunction and use of other add-on strategies. The choice of a specific strategy should be customized to individual needs of the patient.

1. Sexual dysfunction due to SSRI
antidepressants: How to manage?

2. Review Article
Sexual dysfunction due to SSRI antidepressants:
How to manage?
Siddharth Sarkar a,
*, Seshadri Harihar b
, Bichitra Nanda Patra c
a
Assistant Professor, Department of Psychiatry, Sree Balaji Medical College and Hospital, Chromepet, Chennai, India
b
Senior Consultant, Department of Psychiatry, Apollo Hospital, Chennai, India
c
Assistant Professor, Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
1. Introduction
Selective Serotonin Reuptake Inhibitors (SSRIs) are antide-
pressants which act primarily through the serotonergic
system in the central nervous system. Due to their efficacy
and fairly good safety profile, they are the most commonly
prescribed antidepressants.1,2
They are prescribed by not only
psychiatrists, but also general physicians and other specia-
lists.3–5
The class of SSRI antidepressants include molecules
like esctialopram, fluoxetine, fluvoxamine, paroxetine and
sertraline. Though these medications have a proven efficacy
for a range of depression and anxiety spectrum disorders,
these drugs are associated with significant sexual side
effects.6–8
The typical SSRI antidepressants, their indications
and side effects are mentioned in Table 1.
A considerable proportion of the patients prescribed SSRI
antidepressants experience sexual side effects.9–11
Such
sexual side effects can manifest as reduced or poor sexual
desire, erectile dysfunction, delayed ejaculation or anorgas-
mia. Despite experiencing such symptoms, patients often do
not spontaneously report such sexual problems. Also, physi-
cians and psychiatrists do not enquire routinely about sexual
side effects of medications. The sexual problems experienced
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x
a r t i c l e i n f o
Article history:
Received 12 April 2015
Accepted 13 July 2015
Available online xxx
Keywords:
Serotonin uptake inhibitors
Erectile dysfunction
Sexual dysfunction
Antidepressant
Drug substitution
a b s t r a c t
Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of commonly prescribed anti-
depressants in clinical practice. Sexual dysfunction is a common side effect of SSRIs, which
often goes unrecognized but adversely affects the quality of life of the patient. This review
takes a look at the occurrence of sexual dysfunction among patients receiving SSRIs from a
clinical viewpoint. The review explores into the possible reasons of such a dysfunction and
the differential diagnoses to be entertained while dealing patients receiving SSRIs and
experiencing sexual dysfunction. The review discusses the management strategies for
addressing such dysfunction due to SSRIs, including cessation or reduction of dose, chang-
ing to another antidepressant, augmentation with another antidepressant, additional use of
medications for erectile dysfunction and use of other add-on strategies. The choice of a
specific strategy should be customized to individual needs of the patient.
# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights
reserved.
* Corresponding author at: Department of Psychiatry, Sree Balaji Medical College and Hospital, #7 Works Road, Chromepet, Chennai 600044,
India. Tel.: +91 9786022145.
E-mail address: sidsarkar22@gmail.com (S. Sarkar).
APME-299; No. of Pages 5
Please cite this article in press as: Sarkar S, et al. Sexual dysfunction due to SSRI antidepressants: How to manage?, Apollo Med. (2015),
http://dx.doi.org/10.1016/j.apme.2015.07.003
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
http://dx.doi.org/10.1016/j.apme.2015.07.003
0976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.

3. may result in poor quality of life and marital dissatisfaction, if
not addressed appropriately. Hence, there is a need for greater
awareness about sexual side effects of SSRIs as well as the
ways of managing it. This brief review takes a look at the
incidence of SSRI-induced sexual side effects, the aetiology
thereof, the differential diagnoses and the management
options for addressing this problem.
2. The extent of SSRI-induced sexual
dysfunction
The incidence of SSRI-induced sexual dysfunction has been
evaluated in clinical trials and prospective observational
studies. These have been summarized in various systematic
reviews and meta-analyses. The mean rate of sexual
dysfunction encountered by patients receiving SSRIs has
been reported to be about 40% in pooled analysis.12
Individual studies have reported the rate of sexual dysfunc-
tion from as low as 7% to more than 70%.9,13
This could
be ascribed to the varied nature in which assessment of
sexual dysfunction has been made and the medication
regimen used.
The reported rates of sexual dysfunction have differed
across the different SSRIs. The rates of sexual dysfunction
have been found to be higher for citalopram (or escitalopram)
and paroxetine, as compared to fluoxetine, fluvoxamine and
sertraline.9
A network meta-analysis of placebo-controlled
randomized trials found that the weighted mean rate of
sexual dysfunction for fluoxetine to be 8.8%, escitalopram to
be 9.3%, paroxetine to be 15.1% and sertraline to be 15.3%.12
However, this analysis did not show statistically significant
differences in the rates of sexual dysfunction between
escitalopram, fluoxetine, paroxetine and sertraline. The rates
of sexual dysfunction in meta-analysis of randomized trials
seem to be lower than observational studies, probably
because randomized trials have been of shorter duration
and had a greater focus on other serious adverse events
during ascertainment. Sexual dysfunction seems to be more
common in men as compared to women.9,14
This might be
primarily accounted for by the erectile dysfunction being the
most common sexual dysfunction among men, but absent
among women. Women receiving SSRIs primarily experience
decreased sexual desire.
The discordance of rates of sexual dysfunction across the
various studies can be attributed to several factors. Firstly,
sexual dysfunction is not an observable phenomenon and
need to be explored by the treating physician. The self-
reported rates of sexual dysfunction due to SSRIs are
considerably lower than rates with systematic inquiry by
the physician about sexual dysfunction.15,16
Thus, the rates of
sexual dysfunction would vary according to whether it is self-
reported or clinician rated, with the sensitivity and training of
the clinician and the privacy afforded. Secondly, the rates of
sexual dysfunction reported also depend upon the assess-
ment instrument utilized. Several standardized question-
naires are available which assess sexual dysfunction, each
with a different perspective of determining sexual dysfunc-
tion.17
Thirdly, the dose of the SSRIs medication may be
variable across the studies, which may also influence the
rates of sexual dysfunction. Fourthly, the frequency of
assessment also may influence the rate of sexual impairment
observed. Sexual dysfunction with SSRIs may emerge after a
few weeks of initiation and may remit spontaneously. Hence,
closely spaced assessments may yield greater rates of sexual
dysfunction that widely spaced ones. Though various factors
explain the difference in the rates of sexual dysfunction
across studies, but the common theme remains that sexual
dysfunction affects a considerable proportion of patients
receiving SSRIs.
3. Aetiology of sexual dysfunction due to SSRI
The sexual response involves both excitatory and inhibitory
mechanisms at the central and peripheral levels.18
It has
been suggested that norepinephrine mediates the central
arousal system via the disinhibition of dopaminergic
system, and possibly through testosterone mechanism.
Serotonergic and neuropeptidergic mechanisms on the
other hand have been implicated in the inhibition of central
sexual arousal. Rather than an absolute inhibitory effect,
serotonin has been suggested to have a modulating effect on
the sexual functioning.19
SSRI comparatively increases
the serotonergic system than the noradrenergic system,
and hence can lead to the occurrence of sexual dysfunction
in the form of impaired desire. The mesolimbic dopami-
nergic activity is reduced due to inhibitory serotonergic
midbrain raphe nuclei projections, which may also result in
reduced desire.20
The delayed ejaculation and anorgasmia
with SSRIs have been attributed to increased serotonergic
tone. This occurs due to inhibition of ejaculation at the level
of the hypothalamus.21
Noradrenergic tone on the other
hand promotes ejaculation, which concurs with the finding
that noradrenergic antidepressants such as amitriptyline
have milder degree of sexual dysfunction as compared
to SSRIs.
Table 1 – Selective serotonin reuptake inhibitors (SSRIs).
Overview
Representative SSRI antidepressants and their usual doses
Escitalopram (5–20 mg/day)
Fluoxetine (20–60 mg/day)
Fluvoxamine (100–300 mg/day)
Paroxetine (12.5–37.5 mg/day)
Sertraline (50–200 mg/day)
Selected typical indications
Depression
Dysthymia
Generalized anxiety disorder
Obsessive compulsive disorder
Panic disorder
Phobic disorders
Mixed anxiety depression
Adjustment disorder
Sexual side effects
Anorgasmia
Decreased sexual desire
Delayed ejaculation
Erectile dysfunction
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x2
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4. 4. Differential diagnoses and approach to
patient
Several other factors that may lead to sexual impairment need
to be considered among patients receiving SSRIs. One of
the major causes of sexual dysfunction in patients who are
receiving SSRI is the psychiatric disorder itself. SSRIs are
prescribed for a host of psychiatric conditions with depression
being the most common of them. It has been observed that the
constellation of depressive symptoms includes decreased
libido and inability to experience adequate pleasure with
sexual intercourse. The rates of sexual dysfunction in
untreated patients of depression has been found to be
considerably high.22,23
Anxiety disorders, the other major
indication for the prescription of SSRIs, are also associated
with sexual dysfunction.24,25
Multiple other disorders are associated with sexual
dysfunction including diabetes, cardiovascular disorders and
metabolic risk factors.26,27
Other medical disorders that are
associated with sexual dysfunction include multiple sclerosis,
Parkinson's disease and others.28,29
Medical disorders may
also be associated with depression by themselves, which may
lead to sexual dysfunction additionally. Medical disorder as a
possible cause of sexual dysfunction needs to be ruled out to
ascribe the problem to SSRI. It would be helpful to understand
when sexual dysfunction was first observed and was it present
prior to depressive symptoms or the initiation of SSRI.
Investigations for the evaluation of sexual dysfunction can
be carried out if a clear history of association with SSRI
initiation or increase in dose is not available. In such cases,
further investigations such as injection of prostaglandins,
penile Doppler ultrasound or nocturnal penile tumescence
testing can be done to clarify the presence of another organic
aetiology.30
5. Management options
SSRI-induced sexual dysfunction can be addressed in various
ways. After being reasonably certain that the sexual dysfunc-
tion can be ascribed to SSRI, a menu of options are available for
the management of this adverse event (Table 2).
The first option is stopping the offending SSRI or reducing
its dose. This strategy stems from the logical expectation that
if SSRI is the cause of sexual dysfunction, cessation of the SSRI
would improve the extent of sexual dysfunction.31
However,
such an approach is likely to exacerbate the symptoms of
primary psychiatric disorder for which SSRI had been
prescribed in the first place. It is true that some psychiatric
disorders may remit with time and may not need maintenance
treatment subsequently. Hence, in cases where the psychiatric
symptoms have resolved, discontinuation or reduction of
doses of SSRI may be a feasible option after discussion with the
patient. Cessation of the SSRI may also be coupled with
consideration for non-pharmacological interventions like
cognitive behaviour therapy (CBT).
The second option is to shift to another antidepressant with
lower propensity to cause sexual dysfunction. This option may
be appealing when symptoms of anxiety or depression are
clinically impairing and pharmacological management is
required. The patient can be prescribed other antidepressants
such as buproprion (up to 300 mg/day), mitrazapine (up to
45 mg/day) or nefazodone (gradually titrated up to 600 mg/
day), which have a lower predilection to produce sexual side
effects. One of the studies had randomized patients having
SSRI-induced sexual dysfunction into nefazodone and sertra-
line.32
Though both the drugs were equally efficacious,
patients on nefazodone reported lesser frequency of sexual
dysfunction as compared to sertraline.
The third option includes augmentation with another
antidepressant. Bupropion has been used for the augmenta-
tion in patients receiving SSRI and experiencing sexual
impairment. While a few studies did find the efficacy of
bupropion in improving sexual functioning among patients
receiving SSRI,33–35
one of the trials, however, did not find
statistically significant benefits in sexual functioning with
add-on bupropion.36
Add-on mirtazapine has not been found
to be better than placebo in female patients taking SSRIs and
experiencing sexual dysfunction.37
In this trial, add-on
olanzapine was found to be better than add-on mirtazapine
in improving sexual satisfaction.
The fourth option includes addition of specific medications
routinely used for the treatment of sexual dysfunction. For a
patient developing erectile dysfunction with SSRI, phosphodi-
esterase 5 (PDE5) inhibitors such as sildenafil (up to 100 mg/
day), taladafil (up to 20 mg/day) or vardenafil (up to 20 mg/day)
can be recommended to counter the sexual dysfunction.
Several studies have assessed the addition of sildenafil to the
SSRI being already prescribed, and found improved outcomes
Table 2 – Approaches for addressing the sexual dysfunction in patients receiving SSRIs.
Option Potential concerns
Stopping/Reduction in the doses of SSRI Exacerbation of the symptoms of the anxiety or depressive disorder after
discontinuation or decreasing dose
Augmentation with another antidepressant Additional side effects as two antidepressants would need to be prescribed
Shift to another antidepressant like nefazodone
or mirtazapine
The other antidepressant may have different side effect profile, and some
of the side effects may be intolerable
Prescribe additional therapy for erectile
dysfunction like sildenafil and taladafil
Acts only on erectile dysfunction, have their own specific side effects
Other adjunct medications Limited demonstrated efficacy in improving sexual dysfunction in these
patients
PDE, Phosphodiesterase; SSRI, Selective Serotonin Reuptake Inhibitor.
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x 3
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5. of the sexual dysfunction.38–41
Similarly, two studies utilizing
taladafil among patients receiving SSRI and experiencing
sexual dysfunction reported improvement in erectile function-
ing and minimal side effects.42,43
A combination of sublingual
testosterone along with sildenafil has shown promising results
among women with SSRI-induced sexual dysfunction.44
The fifth option includes prescribing another non-antide-
pressant add-on medication for improving sexual functioning.
This includes medications such as amantadine, buspirone,
ephedrine, granisetron and yohimbine.37,45–49
Barring a few
reports,49
the results of these studies have been largely
negative, and robust benefits have not been observed. The
alternative and complementary medicine treatments that
have been tried in this population include ginseng biloba and
maca root, again with minimal objective benefits.50–52
6. Which option to choose
Given the variety of options available for managing SSRI-
induced sexual dysfunction, which one to choose might be a
complicated issue in the clinical setting. The choice of
management option is guided by the illness characteristics,
patient preferences, therapist's comfort with different options
and the characteristics of the sexual history of the patient. For
a patient who had suffered from a serious episode of
depression and has recovered well with medication, stopping
the SSRI or reducing the dose may be best avoided. In such
circumstances, shifting to another antidepressant or adding
PDE5 inhibitors may be the prudent option. In situations when
patient is being prescribed SSRI for a mild anxiety disorder and
experiences further anxiety and marital strain due to sexual
inadequacy, stopping the SSRI would be a rather appealing
option. Some patients may benefit with use of CBT in such
circumstances. An individual with multi-factorial cause for
sexual dysfunction including medical illness such as diabetes,
partially remitted depression and SSRIs, symptomatic man-
agement of erectile dysfunction with PDE5 inhibitors may be
the option of choice. Hence, the selection of management
strategy would be best customized to the needs of individual
patient and the specific circumstances of the case.
To conclude, SSRI-induced sexual dysfunction is a common
occurrence among the clinical population, but often goes
unrecognized. Clinicians need to be aware of this adverse effect
to extend better care to the patients. Various management
strategies are available to address such problem, and the choice
of strategy needs to be individualized to each specific case.
Conflicts of interest
The authors have none to declare.
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a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x 5
APME-299; No. of Pages 5
Please cite this article in press as: Sarkar S, et al. Sexual dysfunction due to SSRI antidepressants: How to manage?, Apollo Med. (2015),
http://dx.doi.org/10.1016/j.apme.2015.07.003

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