The Open Women’ Health Journal, 2007, 1, 1-3

1

Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction
Following Discontinuation of Citalopram and the Atypical AntidepressantNefazodone
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 symptoms 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 ofpersistent sexual dysfunction and genital anesthesia persisting well after termination of SSRI antidepressant therapy havesurfaced. 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 weeksof therapy due to genital anesthesia and orgasmic dysfunction. These symptoms continued following institution of nefazodone therapy and have persisted for over a year since termination of antidepressant treatment. Her depression remains infull remission.
Discussion: It is likely that persistent post-treatment genital anesthesia and other sexual side effects are underreported, andphysicians should be aware of this bothersome phenomenon. Formal post-treatment surveillance for this condition is warranted. 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.
INTRODUCTIONThe serotonin reuptake inhibitor (SSRI) antidepressants
are associated with an array of sexual side effects including
diminished libido, delayed orgasm, anorgasmia, erectile dysfunction or vaginal xerosis, and decreased tactile sensitivity
in the genital region [1,2]. Activation of the 5-HT2A subclassof 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 sexualside effects. Nefazodone is a potent antagonist at the postsynaptic 5-HT2A receptor site with moderate serotonin andnoradrenergic reuptake inhibition. This unique pharmacologic profile likely explains the low order of sexual sideeffects associated with usage [2-5]. Nefazodone has been
administered in conjunction with SSRIs in an effort to counteract the undesirable sexual symptoms associated with thelatter [1-3,5,6]. Alternatively, nefazodone may be substituted
for a SSRI in patients with major depression. Although exceedingly rare, fulminate hepatotoxicity has been reported
following nefazodone administration (one case of death orliver 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 andGynecology, Texas Tech University Health Sciences Center, School ofMedicine, 1400 Coulter Drive, Amarillo, Texas 79106 USA; Tel:806.356.4608; Fax: 806.354.5516; E-mail: robert.kauffman@ttuhsc.edu
1874-291/07

It is expected that sexual functioning rapidly returns tonormal once antidepressants are discontinued, but recently,isolated reports of sustained sexual side effects persisting
months or years after discontinuation of SSRI’s have surfaced in the literature [8,9]. In each case, depressive symptoms were reported to be in remission and no alternative etiology could be identified.
We present a case of persistent genital anesthesia anddiminished libido which has persisted for over one year following completion of a brief course of citalopram followedby prolonged nefazodone treatment.
CASE REPORTA 32 year old woman presented with a six month historyof depressed mood, anhedonia, and difficulty falling asleep.
A prior history of depression and other psychiatric disorders
was absent. The patient denied diminished libido or difficulty achieving orgasm. No significant marital conflicts orother stressors were identified. Her past medical history andphysical 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 thepatient was a sensation of “feeling totally numb” in her genital region with a greatly diminished capacity to respond toclitoral and labial tactile stimulation during intercourse.
Her depressive symptoms improved considerably at 4weeks but the sexual side effects persisted. She requested achange in drug therapy rather than taking a “wait and see”
2007 Bentham Science Publishers Ltd.

2 The Open Women’ Health Journal, 2007, Volume 1

approach. Nefazodone was prescribed and citalopram tapered over one week. She achieved an excellent clinical response to nefazodone 200 mg twice daily, but unfortunately,
the sexual side effects and genital anesthesia continued unabated for the duration of therapy. Bupropion (on a continuous basis) and then sildenafil (prior to intercourse) wereadded to her therapeutic regimen, but the patient failed toexperience 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 oftreatment. Lubrication and genital engorgement remainedintact. The patient maintained regular, cyclic menses before,during, and after treatment.
Neurological examination was normal. Thyrotropin, freethyroxine, serum testosterone, sex hormone binding globulin, and calculated free androgen index were within normallimits. Formal psychological consultation and testing wereobtained, but no residual psychopathology was identified.
DISCUSSION
Sexual side-effects associated with neuropsychiatricdrugs, particularly the SSRI class, are relatively common,and it has been generally assumed that these annoying symptoms 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, studiesof nefazodone have consistently reported a low incidence ofsexual side effects [3,10,11]. In a series of 593 patientstreated with nefazodone from four clinical trials, abnormalorgasm was reported in only 0.2% of the participants [5].
Montejo, et al. pinpointed sexual dysfunction in 4 of 50 depressed patients (8%) treated with nefazodone [10].
Although an element of impaired sexual functioning is
encountered in approximately 40-50% of depressed individuals [4,12], reduced or absent genital sensation has notbeen associated with depression or any other common psychiatric entity [13]. Genital anesthesia appears uniquely associated 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 sixyears following discontinuation of sertraline [8]. Csoka andShipko reported three additional cases of sustained genital
anesthesia and poor libido following treatment with either
fluoxetine, sertraline, or citalopram [9]. In each of thesecases, the onset of unwanted sexual side effects first occurred during SSRI therapy, and residual depressive symptoms were absent at follow up. Yet another study at leastindirectly implicated paroxetine although patients in thatinvestigation were continued on amineptine, an atypical tricyclic antidepressant not associated with sexual dysfunction,
following paroxetine discontinuation [14]. Bahrick has proposed that persistent genital anesthesia and orgasmic hypointensity should be considered putative markers of past SSRI

Kauffman and Murdock

exposure if the condition arose initially during treatment[13].
In addition to these case reports, the emergence of anInternet community comprised of individuals claiming persistent sexual dysfunction following discontinuation of various SSRI’s, albeit unsubstantiated, suggests that this phenomenon may not be rare [13]. Plainly, such an event presents a consequential quality of life issue affecting postdepression sexual functioning with the capacity to compromise intimate relationships in men and women alike.
Early studies of fluoxetine concluded that sexual dysfunction 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 sideeffects following antidepressant therapy would likely resultin underreporting of these events. Accordingly, persistenceof orgasmic dysfunction and loss of genital tactile sensation
following antidepressant discontinuation may be more common than suspected.
The mechanism of antidepressant induced sexual dysfunction is not fully understood which renders speculation on
the psychoneuroendocrinological basis of sustained posttreatment sexual symptoms even more challenging. Permanent changes in serotonin transmission physiology manifested by diminished sexual behavior have been reported inmurine models following neonatal or adolescent SSRI exposure [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 anassociation between a specific 5-HT2A single nucleotide
polymorphism (SNP) and sexual side effects in a mixed gender group of individuals receiving SSRIs [18]. This finding
raises the possibility that a specific SNP might predispose
affected individuals to persistent post-treatment sexual dysfunction.
Persistent sexual dysfunction and genital anesthesia following 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 hypothesize that the unusual nefazodone-treated patient who suffers
sexual side-effects could also develop prolonged posttreatment sexual side effects similar to individuals treatedwith traditional SSRIs.
Long term follow up will be crucial in order to determine
if antidepressant induced sexual dysfunction remains a permanent phenomenon. Continued research into antidepressant
pharmacogenomics may ultimately establish precisely who ispredisposed to this perplexing problem and the molecularbasis involved. In addition, a multi-institutional long term
surveillance project designed to detect the true incidence of
persistent post-antidepressant genital anesthesia and sexualdysfunction should be undertaken. If a positive association isfound, this would have implications for pre-treatment informed consent and could precipitate yet another “blackbox” warning by the FDA.

Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction

The Open Women’ Health Journal, 2007, Volume 1

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Revised: November 16, 2007

Accepted: November 19, 2007