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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 Antidepressant
Nefazodone
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.
INTRODUCTION
It is expected that sexual functioning rapidly returns to normal once antidepressants are discontinued, but recently, The serotonin reuptake inhibitor (SSRI) antidepressants isolated reports of sustained sexual side effects persisting are associated with an array of sexual side effects including months or years after discontinuation of SSRI’s have sur- diminished libido, delayed orgasm, anorgasmia, erectile dys- faced in the literature [8,9]. In each case, depressive symp- function or vaginal xerosis, and decreased tactile sensitivity toms were reported to be in remission and no alternative eti- 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]. We present a case of persistent genital anesthesia and diminished libido which has persisted for over one year fol- Nefazodone is structurally and pharmacologically distinct lowing completion of a brief course of citalopram followed 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 CASE REPORT
noradrenergic reuptake inhibition. This unique pharma- A 32 year old woman presented with a six month history cologic profile likely explains the low order of sexual side of depressed mood, anhedonia, and difficulty falling asleep. effects associated with usage [2-5]. Nefazodone has been A prior history of depression and other psychiatric disorders administered in conjunction with SSRIs in an effort to coun- was absent. The patient denied diminished libido or diffi- teract the undesirable sexual symptoms associated with the culty achieving orgasm. No significant marital conflicts or latter [1-3,5,6]. Alternatively, nefazodone may be substituted other stressors were identified. Her past medical history and for a SSRI in patients with major depression. Although ex- physical examination were normal. Citalopram 20 mg daily 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 Within days of beginning citalopram therapy, she noted a fairness, physicians and consumers should be aware that substantial decrease in libido, difficulty achieving orgasm, drug induced liver injury (usually reversible) has been rarely and diminished orgasmic intensity. Most distressing to the associated with essentially all antidepressant agents [7]. 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. *Address correspondence to this author at the Department of Obstetrics and Her depressive symptoms improved considerably at 4 Gynecology, Texas Tech University Health Sciences Center, School of weeks but the sexual side effects persisted. She requested a Medicine, 1400 Coulter Drive, Amarillo, Texas 79106 USA; Tel: change in drug therapy rather than taking a “wait and see” 806.356.4608; Fax: 806.354.5516; E-mail: robert.kauffman@ttuhsc.edu 1874-2912/07
2007 Bentham Science Publishers Ltd.
2 The Open Women’ Health Journal, 2007, Volume 1
Kauffman and Murdock
approach. Nefazodone was prescribed and citalopram ta- exposure if the condition arose initially during treatment pered over one week. She achieved an excellent clinical re- sponse to nefazodone 200 mg twice daily, but unfortunately, In addition to these case reports, the emergence of an the sexual side effects and genital anesthesia continued un- Internet community comprised of individuals claiming per- abated for the duration of therapy. Bupropion (on a continu- sistent sexual dysfunction following discontinuation of vari- ous basis) and then sildenafil (prior to intercourse) were ous SSRI’s, albeit unsubstantiated, suggests that this phe- added to her therapeutic regimen, but the patient failed to nomenon may not be rare [13]. Plainly, such an event pre- sents a consequential quality of life issue affecting post- Nefazodone was discontinued after 14 months, and her depression sexual functioning with the capacity to compro- depression remained in full remission. One year following mise intimate relationships in men and women alike. completion of drug therapy, she continued to complain of Early studies of fluoxetine concluded that sexual dys- low libido, minimal genital tactile sensation, and orgasmic function occurred in only 2-16% of those receiving the drug, dysfunction that was essentially unchanged from the time of but these numbers were based primarily on patient-based treatment. Lubrication and genital engorgement remained voluntary reporting rather than sophisticated questionnaires intact. The patient maintained regular, cyclic menses before, or direct interview [15]. In the same vein, lack of long term follow up or failure to inquire about sustained sexual side Neurological examination was normal. Thyrotropin, free effects following antidepressant therapy would likely result thyroxine, serum testosterone, sex hormone binding globu- in underreporting of these events. Accordingly, persistence lin, and calculated free androgen index were within normal of orgasmic dysfunction and loss of genital tactile sensation limits. Formal psychological consultation and testing were following antidepressant discontinuation may be more com- obtained, but no residual psychopathology was identified. DISCUSSION
The mechanism of antidepressant induced sexual dys- function is not fully understood which renders speculation on Sexual side-effects associated with neuropsychiatric the psychoneuroendocrinological basis of sustained post- drugs, particularly the SSRI class, are relatively common, treatment sexual symptoms even more challenging. Perma- and it has been generally assumed that these annoying symp- nent changes in serotonin transmission physiology mani- toms abate with discontinuation of treatment. In this regard, fested by diminished sexual behavior have been reported in the absence of a coordinated post-treatment surveillance murine models following neonatal or adolescent SSRI expo- study validating this axiom is surprising. sure [16,17], and hence, it is biologically plausible that an SSRI related sexual side effects have ranged from 58% analogous alteration of serotonin receptor neurophysiology for fluoxetine to 73% for citalopram [10]. In contrast, studies might persist in adult humans. Bishop, et al. identified an of nefazodone have consistently reported a low incidence of association between a specific 5-HT2A single nucleotide sexual side effects [3,10,11]. In a series of 593 patients polymorphism (SNP) and sexual side effects in a mixed gen- treated with nefazodone from four clinical trials, abnormal der group of individuals receiving SSRIs [18]. This finding orgasm was reported in only 0.2% of the participants [5]. raises the possibility that a specific SNP might predispose Montejo, et al. pinpointed sexual dysfunction in 4 of 50 de- affected individuals to persistent post-treatment sexual dys- pressed patients (8%) treated with nefazodone [10]. Although an element of impaired sexual functioning is Persistent sexual dysfunction and genital anesthesia fol- encountered in approximately 40-50% of depressed indi- lowing citalopram administration has been described in one viduals [4,12], reduced or absent genital sensation has not other case report, but there are no published reports of these been associated with depression or any other common psy- symptoms following nefazodone therapy [9]. Parenthetically, chiatric entity [13]. Genital anesthesia appears uniquely as- it is entirely possible that this patient’s condition is entirely sociated with the use of serotonergic antidepressants [1]. attributable to citalopram even though her length of exposure Ordinarily, antidepressant induced sexual side effects rapidly was only four weeks. Nevertheless, it is logical to hypothe- diminish with termination of drug therapy [1,6], but recent size that the unusual nefazodone-treated patient who suffers case reports suggest that this is not always the case. Bolton, sexual side-effects could also develop prolonged post- et al. described persistence of orgasmic dysfunction, genital treatment sexual side effects similar to individuals treated anesthesia, and diminished libido in a 26 year old male six years following discontinuation of sertraline [8]. Csoka and Long term follow up will be crucial in order to determine Shipko reported three additional cases of sustained genital if antidepressant induced sexual dysfunction remains a per- anesthesia and poor libido following treatment with either manent phenomenon. Continued research into antidepressant fluoxetine, sertraline, or citalopram [9]. In each of these pharmacogenomics may ultimately establish precisely who is cases, the onset of unwanted sexual side effects first oc- predisposed to this perplexing problem and the molecular curred during SSRI therapy, and residual depressive symp- basis involved. In addition, a multi-institutional long term toms were absent at follow up. Yet another study at least surveillance project designed to detect the true incidence of indirectly implicated paroxetine although patients in that persistent post-antidepressant genital anesthesia and sexual investigation were continued on amineptine, an atypical tri- dysfunction should be undertaken. If a positive association is cyclic antidepressant not associated with sexual dysfunction, found, this would have implications for pre-treatment in- following paroxetine discontinuation [14]. Bahrick has pro- formed consent and could precipitate yet another “black posed that persistent genital anesthesia and orgasmic hypo- intensity should be considered putative markers of past SSRI Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction
The Open Women’ Health Journal, 2007, Volume 1 3
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