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Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone



SSRI therapy is commonly associated with sexual side effects, but it is assumed that these distressing symp-toms resolve with termination of therapy. The atypical antidepressant nefazodone is infrequently associated with sexual dysfunction and may be substituted for SSRI's when sexual symptoms are intolerable. Recently, scattered case reports of persistent sexual dysfunction and genital anesthesia persisting well after termination of SSRI antidepressant therapy have surfaced. In each case, the underlying depressive disorder was in remission. Case: A 32-year old women with major depression was treated with citalopram but switched to nefazodone after 4 weeks of therapy due to genital anesthesia and orgasmic dysfunction. These symptoms continued following institution of nefa-zodone therapy and have persisted for over a year since termination of antidepressant treatment. Her depression remains in full remission. Discussion: It is likely that persistent post-treatment genital anesthesia and other sexual side effects are underreported, and physicians should be aware of this bothersome phenomenon. Formal post-treatment surveillance for this condition is war-ranted. Pharmacogenomic research may ultimately allow physicians to predict who is at risk for antidepressant induced sexual side effects.
The Open Women’ Health Journal, 2007, 1, 1-3 1
1874-2912/07 2007 Bentham Science Publishers Ltd.
Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction
Following Discontinuation of Citalopram and the Atypical Antidepressant
Robert P. Kauffman* and Amanda Murdock
Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, School of Medicine, 1400
Coulter Drive, Amarillo, Texas 79106 USA
Abstract: SSRI therapy is commonly associated with sexual side effects, but it is assumed that these distressing symp-
toms resolve with termination of therapy. The atypical antidepressant nefazodone is infrequently associated with sexual
dysfunction and may be substituted for SSRI’s when sexual symptoms are intolerable. Recently, scattered case reports of
persistent sexual dysfunction and genital anesthesia persisting well after termination of SSRI antidepressant therapy have
surfaced. In each case, the underlying depressive disorder was in remission.
Case: A 32-year old women with major depression was treated with citalopram but switched to nefazodone after 4 weeks
of therapy due to genital anesthesia and orgasmic dysfunction. These symptoms continued following institution of nefa-
zodone therapy and have persisted for over a year since termination of antidepressant treatment. Her depression remains in
full remission.
Discussion: It is likely that persistent post-treatment genital anesthesia and other sexual side effects are underreported, and
physicians should be aware of this bothersome phenomenon. Formal post-treatment surveillance for this condition is war-
ranted. Pharmacogenomic research may ultimately allow physicians to predict who is at risk for antidepressant induced
sexual side effects.
Keywords: Citalopram, SSRI, nefazodone, sexual dysfunction, genital anesthesia.
The serotonin reuptake inhibitor (SSRI) antidepressants
are associated with an array of sexual side effects including
diminished libido, delayed orgasm, anorgasmia, erectile dys-
function or vaginal xerosis, and decreased tactile sensitivity
in the genital region [1,2]. Activation of the 5-HT2A subclass
of serotonin receptors appears to account for these untoward
side effects [2,3].
Nefazodone is structurally and pharmacologically distinct
form the SSRI class and infrequently associated with sexual
side effects. Nefazodone is a potent antagonist at the post-
synaptic 5-HT2A receptor site with moderate serotonin and
noradrenergic reuptake inhibition. This unique pharma-
cologic profile likely explains the low order of sexual side
effects associated with usage [2-5]. Nefazodone has been
administered in conjunction with SSRIs in an effort to coun-
teract the undesirable sexual symptoms associated with the
latter [1-3,5,6]. Alternatively, nefazodone may be substituted
for a SSRI in patients with major depression. Although ex-
ceedingly rare, fulminate hepatotoxicity has been reported
following nefazodone administration (one case of death or
liver transplant per 250,000 patients treated per year). In
fairness, physicians and consumers should be aware that
drug induced liver injury (usually reversible) has been rarely
associated with essentially all antidepressant agents [7].
*Address correspondence to this author at the Department of Obstetrics and
Gynecology, Texas Tech University Health Sciences Center, School of
Medicine, 1400 Coulter Drive, Amarillo, Texas 79106 USA; Tel:
806.356.4608; Fax: 806.354.5516; E-mail:
It is expected that sexual functioning rapidly returns to
normal once antidepressants are discontinued, but recently,
isolated reports of sustained sexual side effects persisting
months or years after discontinuation of SSRI’s have sur-
faced in the literature [8,9]. In each case, depressive symp-
toms were reported to be in remission and no alternative eti-
ology could be identified.
We present a case of persistent genital anesthesia and
diminished libido which has persisted for over one year fol-
lowing completion of a brief course of citalopram followed
by prolonged nefazodone treatment.
A 32 year old woman presented with a six month history
of depressed mood, anhedonia, and difficulty falling asleep.
A prior history of depression and other psychiatric disorders
was absent. The patient denied diminished libido or diffi-
culty achieving orgasm. No significant marital conflicts or
other stressors were identified. Her past medical history and
physical examination were normal. Citalopram 20 mg daily
was prescribed for major depression.
Within days of beginning citalopram therapy, she noted a
substantial decrease in libido, difficulty achieving orgasm,
and diminished orgasmic intensity. Most distressing to the
patient was a sensation of “feeling totally numb” in her geni-
tal region with a greatly diminished capacity to respond to
clitoral and labial tactile stimulation during intercourse.
Her depressive symptoms improved considerably at 4
weeks but the sexual side effects persisted. She requested a
change in drug therapy rather than taking a “wait and see”
2 The Open Women’ Health Journal, 2007, Volume 1 Kauffman and Murdock
approach. Nefazodone was prescribed and citalopram ta-
pered over one week. She achieved an excellent clinical re-
sponse to nefazodone 200 mg twice daily, but unfortunately,
the sexual side effects and genital anesthesia continued un-
abated for the duration of therapy. Bupropion (on a continu-
ous basis) and then sildenafil (prior to intercourse) were
added to her therapeutic regimen, but the patient failed to
experience any improvement.
Nefazodone was discontinued after 14 months, and her
depression remained in full remission. One year following
completion of drug therapy, she continued to complain of
low libido, minimal genital tactile sensation, and orgasmic
dysfunction that was essentially unchanged from the time of
treatment. Lubrication and genital engorgement remained
intact. The patient maintained regular, cyclic menses before,
during, and after treatment.
Neurological examination was normal. Thyrotropin, free
thyroxine, serum testosterone, sex hormone binding globu-
lin, and calculated free androgen index were within normal
limits. Formal psychological consultation and testing were
obtained, but no residual psychopathology was identified.
Sexual side-effects associated with neuropsychiatric
drugs, particularly the SSRI class, are relatively common,
and it has been generally assumed that these annoying symp-
toms abate with discontinuation of treatment. In this regard,
the absence of a coordinated post-treatment surveillance
study validating this axiom is surprising.
SSRI related sexual side effects have ranged from 58%
for fluoxetine to 73% for citalopram [10]. In contrast, studies
of nefazodone have consistently reported a low incidence of
sexual side effects [3,10,11]. In a series of 593 patients
treated with nefazodone from four clinical trials, abnormal
orgasm was reported in only 0.2% of the participants [5].
Montejo, et al. pinpointed sexual dysfunction in 4 of 50 de-
pressed patients (8%) treated with nefazodone [10].
Although an element of impaired sexual functioning is
encountered in approximately 40-50% of depressed indi-
viduals [4,12], reduced or absent genital sensation has not
been associated with depression or any other common psy-
chiatric entity [13]. Genital anesthesia appears uniquely as-
sociated with the use of serotonergic antidepressants [1].
Ordinarily, antidepressant induced sexual side effects rapidly
diminish with termination of drug therapy [1,6], but recent
case reports suggest that this is not always the case. Bolton,
et al. described persistence of orgasmic dysfunction, genital
anesthesia, and diminished libido in a 26 year old male six
years following discontinuation of sertraline [8]. Csoka and
Shipko reported three additional cases of sustained genital
anesthesia and poor libido following treatment with either
fluoxetine, sertraline, or citalopram [9]. In each of these
cases, the onset of unwanted sexual side effects first oc-
curred during SSRI therapy, and residual depressive symp-
toms were absent at follow up. Yet another study at least
indirectly implicated paroxetine although patients in that
investigation were continued on amineptine, an atypical tri-
cyclic antidepressant not associated with sexual dysfunction,
following paroxetine discontinuation [14]. Bahrick has pro-
posed that persistent genital anesthesia and orgasmic hypo-
intensity should be considered putative markers of past SSRI
exposure if the condition arose initially during treatment
In addition to these case reports, the emergence of an
Internet community comprised of individuals claiming per-
sistent sexual dysfunction following discontinuation of vari-
ous SSRI’s, albeit unsubstantiated, suggests that this phe-
nomenon may not be rare [13]. Plainly, such an event pre-
sents a consequential quality of life issue affecting post-
depression sexual functioning with the capacity to compro-
mise intimate relationships in men and women alike.
Early studies of fluoxetine concluded that sexual dys-
function occurred in only 2-16% of those receiving the drug,
but these numbers were based primarily on patient-based
voluntary reporting rather than sophisticated questionnaires
or direct interview [15]. In the same vein, lack of long term
follow up or failure to inquire about sustained sexual side
effects following antidepressant therapy would likely result
in underreporting of these events. Accordingly, persistence
of orgasmic dysfunction and loss of genital tactile sensation
following antidepressant discontinuation may be more com-
mon than suspected.
The mechanism of antidepressant induced sexual dys-
function is not fully understood which renders speculation on
the psychoneuroendocrinological basis of sustained post-
treatment sexual symptoms even more challenging. Perma-
nent changes in serotonin transmission physiology mani-
fested by diminished sexual behavior have been reported in
murine models following neonatal or adolescent SSRI expo-
sure [16,17], and hence, it is biologically plausible that an
analogous alteration of serotonin receptor neurophysiology
might persist in adult humans. Bishop, et al. identified an
association between a specific 5-HT2A single nucleotide
polymorphism (SNP) and sexual side effects in a mixed gen-
der group of individuals receiving SSRIs [18]. This finding
raises the possibility that a specific SNP might predispose
affected individuals to persistent post-treatment sexual dys-
Persistent sexual dysfunction and genital anesthesia fol-
lowing citalopram administration has been described in one
other case report, but there are no published reports of these
symptoms following nefazodone therapy [9]. Parenthetically,
it is entirely possible that this patient’s condition is entirely
attributable to citalopram even though her length of exposure
was only four weeks. Nevertheless, it is logical to hypothe-
size that the unusual nefazodone-treated patient who suffers
sexual side-effects could also develop prolonged post-
treatment sexual side effects similar to individuals treated
with traditional SSRIs.
Long term follow up will be crucial in order to determine
if antidepressant induced sexual dysfunction remains a per-
manent phenomenon. Continued research into antidepressant
pharmacogenomics may ultimately establish precisely who is
predisposed to this perplexing problem and the molecular
basis involved. In addition, a multi-institutional long term
surveillance project designed to detect the true incidence of
persistent post-antidepressant genital anesthesia and sexual
dysfunction should be undertaken. If a positive association is
found, this would have implications for pre-treatment in-
formed consent and could precipitate yet another “black
box” warning by the FDA.
Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction The Open Women’ Health Journal, 2007, Volume 1 3
[1] Zajecka J. Strategies for the treatment of antidepressant-related
sexual dysfunction. J Clin Psychiat 2001; 62 Suppl 3: 35.
[2] Clayton AH, Montejo AL. Major depressive disorder, antidepres-
sants, and sexual dysfunction. J Clin Psychiat 2006;67 Suppl 6: 33.
[3] DeVane C, Grothe D, Smith S. Pharmacology of antidepressants:
Focus on nefazodone. J Clin Psychiat 2002; 63: 10.
[4] Zajecka J, Dunner DL, Gelenberg AJ, et al. Sexual function and
satisfaction in the treatment of chronic major depression with nefa-
zodone, psychotherapy, and their combination. J Clin Psychiat
2002; 63: 709.
[5] Augustin B, Cold J, Jann M. Venlafaxine and nefazodone two
pharmacologically distinct antidepressants. Pharmacotherapy 1997;
71: 511.
[6] Ferguson JM. The effects of antidepressants on sexual functioning
in depressed patients: A review. J Clin Psychiat 2001; 62 Suppl 3:
[7] DeSanty KP, Amabile CM. Antidepressant-induced liver injury.
Ann Pharmacother 2007; 41: 1201.
[8] Bolton J, Sareen J, Reiss J. Genital anaesthesia persisting six years
after sertraline discontinuation. J Sex Marital Ther 2006; 32: 327.
[9] Csoka A, Shipko S. Persistent sexual side effects after SSRI dis-
continuation. Psychother Psychosom 2006; 75: 187.
[10] Montejo AL, Llorca G, Izquierdo JA, et al. Incidence of sexual
dysfunction associated with antidepressant agents: A prospective
multicenter study of 1022 outpatients. Spanish Working Group for
the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psy-
chiat 2001; 62 Suppl 3: 10.
[11] Taylor MJ, Rudkin L, Hawton K. Strategies for managing antide-
pressant-induced sexual dysfunction: Systematic review of random-
ised controlled trials. J Affect Disord 2005; 88: 241.
[12] Kennedy SH, Dickens SE, Eisfeld BS, Bagby RM. Sexual dysfunc-
tion before antidepressant therapy in major depression. J Affect
Disord 1999; 56: 201.
[13] Bahrick A. Post SSRI sexual dysfunction. ASAP Tablet 2006; 7: 2-
3, 10.
[14] Montejo AL, Llorca G, Izquierdo JA, et al. Sexual dysfunction
with antidepressive agents. Effect of the change to amineptine in
patients with sexual dysfunction secondary to SSRI. Actas Esp
Psiquiatr 1999; 27: 23.
[15] Zajecka J, Fawcett J, Schaff M, Jeffriess H, Guy C. The role of
serotonin in sexual dysfunction: fluoxetine-associated orgasm dys-
function. J Clin Psychiat1991; 52: 66.
[16] Maciag D, Simpson K, Coppinger D, et al. Neonatal antidepressant
exposure has lasting effects on behavior and serotonin circuitry.
Neuropsychopharmacology 2006; 31: 47.
[17] DeJong T, Snaphaan L, Pattij T, et al. Effects of chronic treatment
with fluvoxamine and paroxetine during adolescence on serotonin-
related behavior in adult male rats. Eur Neuropsychopharmacol
2006; 16: 39.
[18] Bishop JR, Moline J, Ellingrod VL, et al. Serotonin 2A -1438 G/A
and G-protein Beta3 subunit C825T polymorphisms in patients
with depression and SSRI-associated sexual side-effects. Neuro-
psychopharmacology 2006; 31: 2281.
Received: November 02, 2007 Revised: November 16, 2007 Accepted: November 19, 2007
... Although sexual dysfunction induced by serotonergic antidepressants is commonly assumed to resolves upon drug discontinuation, it persists in some patients despite cessation of antidepressant treatment, a condition known as post-SSRI sexual dysfunction (PSSD) [5,8,10,12]. It should be noted that although its name would suggest that PSSD refers only to SSRIs, it has been described with other antidepressant that act on serotonin (e.g., serotonin-norepinephrine reuptake inhibitors [8,13], nephzodone [11]) and is defined here as such. Finally, in June of 2019, PSSD gained an official recognition by the European Medicines Agency as a sexual dysfunction that can endure after SSRI\SNRI treatment stops [14]. ...
Full-text available
Background Sexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs. Methods A 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21–49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively). Results SAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI 2.8–4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI 2.3–4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000. Conclusions This work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.
... In PSSD, the general approach focuses on manipulating the serotonergic and dopaminergic systems, for example by adding 5-HT-2 and 5-HT-3 antagonists such as trazadone and mirtazapine [17,23,24,38,39,41,49] or dopamine agonists [16] such as pramipexole [17,23,24,30,38,39,41] and cabergoline [17,23,24,38,39,41,47] and 5-HT1A agonist as buspirone [17,23,24,38,39,47]. These treatments go along with phospodiesterase type 5 inhibitors (IPDE5) [4,14,17,23,24,38,39,41,47,49,50] as shown in Figure 2. ...
Background : Sexual dysfunction is highly prevalent worldwide. A specific form is persistent sexual dysfunction after SSRI withdrawal. We conducted a systematic literature review in order to characterize factors related to post SSRI sexual dysfunction (PSSD) and analyzed spontaneous reports of persistent sexual dysfunction reported to the Netherlands Pharmacovigilance Centre Lareb. Research Design and Methods A systematic literature review was conducted following the PRISMA-ScR guidelines. In addition, reports of PSSD submitted to the Netherlands Pharmacovigilance Centre Lareb between 1992 and 2021 were analyzed. Results : A total of 237 articles were retrieved through the search and 33 articles were selected for inclusion in this review, in accordance with the inclusion criteria. Information regarding the characteristics of the condition, it’s clinical management, patient characteristics and impact of PSSD is presented. A total of 86 reports of persistent sexual dysfunction, were analyzed. The longest case being a patient with PSSD for 23 years. The main symptoms were: loss or decreased libido (n= 53), erectile dysfunction (n= 23) and anorgasmia (n= 5). Conclusions PSSD impact includes sexual, psychological and social consequences. Little is known about the mechanisms underlying PSSD and no effective treatment exists. It is necessary to increase recognition of PSSD among prescribers and improve its management at the clinical level.
... In PSSD there is a marked escalation of genital sensory effects [22,23]. Some describe reduced somatic (tactile) sensation -genitals feel like they were exposed to an anesthetic. ...
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Background: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin. Objective: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD). Methods: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts. Results: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor. Conclusions: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.
... In 2007, Kauffman and Murdock reported the case of a 32-year-old female who developed genital anesthesia, diminished orgasmic intensity, diffi culty achieving orgasm, and a substantial decrease in libido within days of starting citalopram [14]. She described her genital region as "feeling totally numb". ...
Full-text available
Article as a citizen petition that leads the EMA (June 2019) to advice the risk of post-SSRI sexual dysfunction in the antidepressants prospect
... The side effects of SSRIs, as reported above, are expected to disappear after discontinuation of their use. However, in 2006, the first reports of enduring sexual side effects from SSRIs appeared following with other reports of comparable cases and the designation of these effects as a post-SSRI sexual dysfunction (PSSD) [21][22][23][24][25][26][27]. On June 11, 2019, the European Medicines Agency (EMA) formally declared that it recognized PSSD as a medical condition that can outlast discontinuation of SSRI and SNRI antidepressants. ...
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Purpose of Review Because of the sex/gender differences in the manifestation of depression, one can assume the possible existence of gender differences in post-SSRI sexual dysfunction (PSSD). This article tries to summarize the available data on sex/gender differences in PSSD and to evaluate if different approaches in diagnosis or treatment of different genders are needed. Recent Findings Depression is a leading cause of disability worldwide. Studies observed gender differences in prevalence and clinical presentation of depression, adherence to treatment and pharmacological features of antidepressant treatment. Sexual adverse events during the use of antidepressants are well-known and occur frequently. PSSD has been recently recognized as a medical condition that can outlast discontinuation of SSRI and SNRI antidepressants. The published literature on PSDD is lacking a clear definition of PSSD and data on possible sex/gender differences are very limited. The available information shows some gender differences in frequency of the different presented symptoms, but development of validated clinical assessment instruments of all possible sexual complaints, including genital anesthesia and pleasureless orgasm, is necessary. Summary The available scientific literature is lacking profound information about the extent, the mechanism, and possible treatment of PSSD and sex/gender differences as well. Physicians should assess sexual function prior, during, and also after treatment with antidepressants and be aware of the possibility of PSSD. Physicians should inform their patients about the possible sexual consequences of antidepressant treatment and include it, when possible, in the treatment decision-making process.
... The first reports of enduring sexual side effects from serotonin reuptake inhibitors appeared in 2006 with further reports and the designation of these effects as a post-SSRI sexual dysfunction (PSSD) following [2][3][4][5][6][7][8]. Since 2011, the US product information for Prozac (fluoxetine) has warned that "Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment." ...
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Objective: To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. Methods: Data from, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities.RESULTSWe report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life.CONCLUSIONS These data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general.
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Introduction: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug for various psychiatric disorders during the lifespan, including pregnancy, lactation, childhood, and adolescence. Deterioration in sexual functioning is a major and serious adverse effect of SSRIs. There is emerging evidence that SSRIs can have long-lasting effects on sexuality. Aim: To summarize the long-lasting effects of SSRIs on sexuality, starting with animal models and continuing with the clinical experience of different investigators. Method: A literature review of relevant publications in PubMed. Main outcome measures: To assess the long-lasting effects of SSRIs on sexuality. Results: Although the persistent effects of SSRIs on sexuality have been little studied in humans, animal studies suggest that SSRIs might cause permanent sexual dysfunction after ending SSRI exposure at a young age but not in adulthood in rats. There are no prospective randomized controlled trials in humans and the present evidence is derived from case reports, incidental research findings, and experiences of some internet communities. Conclusion: There is some preclinical evidence from animal studies for enduring SSRI-induced sexual dysfunction, but the available clinical information could prevent a clear decision about the existence of post-SSRI sexual dysfunction, its pathophysiology, and its management. We need more research to fill in the gaps in our knowledge. Coskuner ER, Culha MG, Ozkan B, Kaleagasi EO. Post-SSRI Sexual Dysfunction: Preclinical to Clinical. Is It Fact or Fiction? Sex Med Rev 2017;X:XXX-XXX.
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Introduction: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug. Post-SSRI sexual dysfunction (PSSD) is a condition in which patients continue to have sexual side effects after discontinuation of SSRI use. The prevalence of persistent sexual side effects after discontinuing SSRIs is unknown. The recognition and study of PSSD will increase our knowledge base of this underreported and distressing condition. Aim: To provide coverage of the current literature on PSSD, update information on the pathophysiology of PSSD, and discuss potential management options. Methods: Comprehensive review of literature pertaining to PSSD. Main outcome measures: The symptoms, classification, pathophysiology, diagnostic considerations, and management of PSSD were reviewed. Results: Common PSSD symptoms include genital anesthesia, pleasure-less or weak orgasm, decreased sex drive, erectile dysfunction, and premature ejaculation. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression theory, cytochrome actions, dopamine-serotonin interactions, proopiomelanocortin and melanocortin effects, serotonin neurotoxicity, downregulation of 5-hydroxytryptamine receptor 1A, and hormonal changes in the central and peripheral nervous systems. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual dysfunction. Treating PSSD is challenging, and many strategies have been suggested and tried, including serotonergic antagonists and dopaminergic agonists. There is still no definitive treatment for PSSD. Low-power laser irradiation and phototherapy have shown some promising results. Conclusion: PSSD is a debilitating condition that adversely affects quality of life. Further studies are warranted to investigate the prevalence, pathophysiology, and treatment of PSSD. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev 2017;X:XXX-XXX.
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Resumen Evidencias recientes sugieren que la disfunción sexual que aparece con frecuencia durante el tratamiento con inhibidores selectivos de la recaptación de serotonina (ISRS) o con los inhibidores selectivos de la recaptación de serotonina y noradrenalina (IRSN) persiste en algunos pacientes tras la discontinuación del tratamiento. Se presenta un caso clínico que sugiere probabilidad elevada para realizar esta atribución causal tras la retirada de paroxetina, según los criterios sugeridos por Ben-Sheetrit et al. en el artículo «Post-SSRI sexual dysfunction»: varón joven sin enfermedad física concurrente, sin tratamientos farmacológicos ni uso de tóxicos (salvo consumo muy moderado y ocasional de alcohol) y libre de síntomas afectivos en el momento actual que pudieran explicar mejor la presencia de disfunción sexual. Doce semanas después de la retirada de paroxetina, persiste disminución de la libido y dificultades moderadas en el mantenimiento de la erección. El creciente interés por la evaluación de la disfunción sexual secundaria a antidepresivos, y el compromiso sobre la esfera sexual de nuestros pacientes, facilita la identificación de casos.
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Sexual dysfunction secondary to the use of antidepressants, especially clomipramine or SSRI's is an adverse effect that is often underestimated and according to earlier studies, this can affect approximately 60% of the patients. This presents as a decrease in libido, alterations in the ability to reach orgasm/ejaculation, and an erectile dysfunction or a decreased vaginal lubrication. This dysfunction appears to be related with the resulting increase in serotonin and with the stimulation of serotonin 5HT2 receptors. 1) Evaluate the effect of amineptine, a drug with an increased dopamine transmission and scant serotonin transmission, on the sexual function of depressed patients who begin treatment, and 2) evaluate whether the change to amineptine improves the sexual function in patients who presented sexual dysfunction after beginning treatment with a SSRI. Prospective, observational, open and multicentric design. 111 patients with an average age of 41.3 years (36 men, 75 women) were distributed into three groups: Group 1 (n= 26): patients with depression (DSM IV) who begin de novo treatment with amineptine 200 mg/day. Group 2 (n= 47): depressed patients undergoing treatment with a SSRI who show a favorable response and who present sexual dysfunction secondary to a poorly tolerated treatment, so the treatment is changed to 200 mg/day of amineptine. Group 3 (n= 38): patients with the same characteristics as those of group 2, but whose treatment was changed to 20 mg/day of paroxetine. The (Montejo et al, 1996) was used together with the Hamilton Depression Scale, the IGC Scale, and an adverse events scale, over a 6 months follow up period during which visits took place at: baseline, month 1, month 2, month 3, and month 6. In group 1, treated with amineptine from the beginning, of the 5 patients who showed a decrease in the libido at the beginning of the treatment, only one still presented this in the 6th month. The Hamilton Scale decreased from 23.12 (baseline) to 5.25 after 6 months. After substituting amineptine for SSRI's in patients with sexual dysfunction, the incidence of any type of sexual dysfunction decreased significantly from 100% (baseline) to 55.3% after 6 months. (P< 0.001). The incidence of delayed orgasm dropped to 15.8%, anorgasmia to 17.4%, and impotence dropped to 15.8% in this group, with the antidepressant effect that had already been achieved with the SSRI being maintained. However, in group 3 there was barely any improvement on the sexual function after changing to paroxetine (20 mg/day), with the baseline incidence being 100% and the incidence after 6 months being 89.7%. In this last group the antidepressant effect present at the baseline level, was maintained. Amineptine was shown to be an effective antidepressant in the patients studied, and did not cause secondary sexual dysfunction, and even improved the dysfunction that was present in some patients. In those patients previously treated with SSRI's, amineptine is able to significantly improve the sexual dysfunction and yet maintain the efficacy of the antidepressive treatment used before these 6 months. On the other hand, Paroxetine did not improve the sexual dysfunction of the people in whom this drug substituted another SSRI, as this is an adverse effect common to the entire group of selective serotonin re-uptake inhibiting drugs. Amineptine showed a good safety and tolerance profile. Its most common side effect (anxiety/restlessness) disappeared 2 months after the beginning of the treatment.
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Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and clomipramine, are frequently associated with sexual dysfunction. Other antidepressants (nefazodone, mirtazapine, bupropion, amineptine, and moclobemide) with different mechanisms of action seem to have fewer sexual side effects. The incidence of sexual dysfunction is underestimated, and the use of a specific questionnaire is needed. The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter, prospective, open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines. One thousand twenty-two outpatients (610 women, 412 men; mean age = 39.8 +/- 11.3 years) were interviewed using the Psychotropic-Related Sexual Dysfunction Questionnaire, which includes questions about libido, orgasm, ejaculation, erectile function, and general sexual satisfaction. The overall incidence of sexual dysfunction was 59.1% (604/1022) when all antidepressants were considered as a whole. There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs: fluoxetine, 57.7% (161/279); sertraline, 62.9% (100/159); fluvoxamine, 62.3% (48/77); paroxetine, 70.7% (147/208); citalopram, 72.7% (48/66); venlafaxine, 67.3% (37/55); mirtazapine, 24.4% (12/49); nefazodone, 8% (4/50); amineptine, 6.9% (2/29); and moclobemide, 3.9% (1/26). Men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%), although women had higher severity. About 40% of patients showed low tolerance of their sexual dysfunction. The incidence of sexual dysfunction with SSRIs and venlafaxine is high, ranging from 58% to 73%, as compared with serotonin-2 (5-HT2) blockers (nefazodone and mirtazapine), moclobemide, and amineptine.
Selective Serotonin Reuptake Inhibitors (SSRIs) are designed to treat adults, but are increasingly prescribed for adolescents. SSRIs might cause permanent changes in serotonin-related behavior in adolescents, since their serotonergic system is still developing. Male Wistar rats were treated with paroxetine (15 mg/kg p.o.) or fluvoxamine (30 mg/kg p.o.) throughout adolescence. After a washout period their behavior in the elevated plusmaze, prepulse inhibition test, Forced swimming test and elevated T-maze were studied. In addition, the effects of the 5-HT1A receptor agonist 8-OH-DPAT on sexual behavior and lower lip retraction were measured. Paroxetine mildly inhibited weight gain during treatment. Both SSRIs caused a reduction in ejaculation frequency and in time spent on the open arm of the elevated plus-maze in adult rats. Fluvoxamine slightly increased avoidance latency in the elevated T-maze compared to paroxetine. No differences between the groups were found in the other tests. Apparently, chronic treatment with SSRIs during adolescence may cause mild changes in adult behavior.
Depression and antidepressant therapy have been associated with sexual dysfunction. Studies report wide discrepancies with regard to frequency, gender, and quality of sexual dysfunction. Although sexual side effects are a common reason for non-compliance with medication, information on impairment of sexuality in psychiatric patients is rare. The impact of antidepressant- induced sexual dysfunction is substantial and negatively affects quality of life, self-esteem, mood, and relationship with partner. Sexual side effects resulting from serotonin specific reuptake inhibitors use may be mediated by a number of central and peripheral mechanisms. Some antidepressants such as Bupropion, mirtazapine, and moclobemide have a sexual tolerability profile significantly better than SSRIs, especially escitalopram, paroxetine, venlafaxine, sertraline, or fluoxetine. There are some possibilities for treatment of anti-depressant induced sexual dysfunctions such as waiting for spontaneous remission, reducing the dosage level, substituting the offending drug with other antidepressants, drug holidays, or administration of a phosphodiesterase- 5-inhibitor. These side-effects are increasingly used therapeutically in the context of the common male sexual dysfunction ejaculatio praecox. For this indication short-acting SSRI;s are available.
Iatrogenic sexual dysfunction has been associated with many pharmacologic agents. The authors report 6 cases of orgasm dysfunction associated with the use of fluorxetine in 77 depressed outpatients. Fluoxetine is a novel antidepressant known to block the reuptake of serotonin with little effect on other neurotransmitter systems. Because fluoxetine has a specific mechanism of action, it serves as a useful model to hypothesize about potential mechanisms of drug-induced sexual dysfunction. The possible effects of serotonin on central, spinal, and peripheral anatomical areas are discussed in relation to drug-induced sexual dysfunction.
Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are the newest antidepressants to receive approval of the Food and Drug Administration and to be marketed in the United States. Both strongly inhibit serotonin (5-HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and nefazodone also exhibits 5-HT2-receptor antagonism. Venlafaxine inhibits the cytochrome P-450 2D6 isozyme to a lesser extent than the selective serotonin reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are unrelated to SSRIs and have some clinically important differences in side effect profiles. Nausea, headache, somnolence, and dry mouth are the most frequently reported side effects with both. Sustained hypertension was reported by a limited number of venlafaxine-treated patients.
Decreased sexual interest and function both occur as a consequence of antidepressant medication use, and are especially associated with serotonin reuptake inhibitors (SRIs). However, few investigators have reported the base rate for disturbances in sexual desire, arousal and orgasm or ejaculation in patients with major depression (MD) prior to antidepressant treatment. The purpose of this report is to define the frequency of sexual dysfunction (SD) in 134 patients with MD and examine the relationship between SD and demographic, clinical and personality variables. A consecutive series of 55 male and 79 female MD patients diagnosed by SCID-DSM IV assessment completed a series of psychometric measures including a Sexual Function Questionnaire, which asked about change in sexual interest and function as well as sexual activity during the preceding month. Only 50% of women and 75% of men reported sexual activity during the preceding month. Over 40% of men and 50% of women reported decreased sexual interest. Reduced levels of arousal were more common in both men and women (40-50%) than ejaculatory or orgasm difficulties (15-20%). In women, problems with arousal and orgasm correlated with higher neuroticism and lower extraversion. There was no relationship between SD and personality measures in men. While age at onset of depression and number of prior episodes showed a modest correlation with SD measures, there were no correlations with severity of depression or specific symptoms clusters. Although limited by a relatively small sample of drug free patients with MD, and by the absence of a non-depressed comparison sample, these results emphasize the importance of factors beyond specific drug effects in the assessment of antidepressant related sexual dysfunction.
Sexual dysfunction and dissatisfaction are common symptoms associated with depression. Optimal antidepressant treatment should result in remission of the symptoms of the underlying illness and minimize the potential for short- and long-term adverse effects, including sexual dysfunction. Sexual dysfunction and dissatisfaction are frequently persistent or worsen with the use of some antidepressant medications; this sexual dysfunction and dissatisfaction can have negative impact on adherence to treatment, quality of life, and the possibility of relapse. Successful management of sexual complaints during antidepressant treatment should begin with a systematic approach to determine the type of sexual dysfunction, potential contributing factors, and finally management strategies that should be tailored to the individual patient. The basic physiologic mechanisms of the normal sexual phases of libido, arousal, and orgasm and how these mechanisms may be interrupted by some antidepressants provide a framework for the clinician to utilize in order to minimize sexual complaints when initiating and continuing antidepressant treatment. This article provides guidelines, based upon this type of model, for the assessment, management, and prevention of sexual side effects associated with antidepressant treatment.
Sexual dysfunction has long been noted as both a symptom of depressive illness and as a side effect of many of the medications used to treat depression. Although most people suffering from a major depressive illness would like to be sexually active, half experience a decrease in desire or sexual performance. Antidepressant medications often interfere with several parts of the sexual response. This review compares data from different types of research into the effect of antidepressant medications on the sexual response: case reports, chart reviews, and single- and double-blind studies with and without active control medications. From this review, it is clear that antidepressants of most classes interfere with human sexual functioning, with the notable exceptions of bupropion and nefazodone.