Nurnberg GH, Hensley PL, Heiman JR, et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial

Department of Psychiatry, University of New Mexico School of Medicine, 2400 Tucker NE, MC 09 5030, Albuquerque, NM 87131-0001, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 07/2008; 300(4):395-404. DOI: 10.1001/jama.300.4.395
Source: PubMed


Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women.
To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women.
An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction.
Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity.
The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed.
In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects.
In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects. Identifier: NCT00375297.

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Available from: H. George Nurnberg, Jul 25, 2014
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    • "Selective serotonin reuptake inhibitors (SSRIs) are the most notorious for causing sexual dysfunction (SD) with an estimated prevalence rate of 20–70% (Serretti and Chiesa, 2009; Montejo et al., 2001). Although some beneficial effects have been reported with the use of buspirone (Landen et al., 1999; Norden, 1994), bupropion (Labbate and Pollack, 1994; Safarinejad, 2011; Clayton et al., 2004) or type 5 phosphopdiesterase (PDE5) inhibitors (e.g., sildenafil) (Nurnberg et al., 2008, 2003; Fava et al., 1998), to date no FDA approved pharmacological treatment for SSRIinduced SD is available. Of the different serotonin (5-HT) receptors, 5-HT 1A and 5-HT 2 receptors are well accepted to be involved in sexual functioning (Clayton and Hamilton, 2009; Berger et al., 2009). "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are known to cause sexual dysfunction, such as decreased sexual motivation, desire, arousal, and orgasm difficulties. These SSRI-induced sexual complaints have a high prevalence rate, while there is no approved pharmacological treatment for SSRI-induced sexual dysfunction. It is hypothesized that a polymorphisms in the androgen receptor gene, encoded by the nucleotides cysteine, adenine, and guanine (CAG), influence the effect of testosterone on sexual functioning. In an explorative, randomized, double-blind, placebo-controlled, crossover study we investigated the possible effects of sublingual testosterone combined with a serotonin (5-HT) 1A receptor agonist, and of sublingual testosterone combined with a phosphodiesterase type 5 inhibitor (PDE5-i) on sexual functioning in women with SSRI-induced sexual dysfunction. Furthermore, we did an exploratory analysis to assess if the CAG polymorphism influences this effect. 21 pre- and postmenopausal women with SSRI-induced sexual dysfunction participated and underwent the following interventions: a combination of testosterone (0.5mg) sublingually and the PDE5-i sildenafil (50mg) and a combination of testosterone (0.5mg) sublingually and the 5-HT1A receptor agonist buspirone (10mg). The results show that women who use a low dose of SSRI and have relatively long CAG repeats report a marked improvement in sexual function in response to both treatments compared to placebo. This explorative study and preliminary results indicate that in women with SSRI-induced sexual dysfunction, a combination of testosterone sublingually and a PDE5-i or testosterone sublingually and a 5-HT1A receptor agonist might be promising treatments for certain subgroups of women with this condition. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 11/2014; 753. DOI:10.1016/j.ejphar.2014.10.061 · 2.53 Impact Factor
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    • "Many adjuvant compounds have been advocated for relieving sexual dysfunction associated with antidepressant drug treatment, though relatively few compounds have been subjected to rigorous evaluation. Randomised placebo-controlled trials indicate probable efficacy for bupropion [40], olanzapine [40], testosterone gel [44], and the phosphodiesterase-5 inhibitors sildenafil (both in male and female patients [45, 46]) and tadalafil [47]. Comparative studies are rare, though a placebo-controlled study found no evidence of efficacy for augmentation with mirtazapine, olanzapine, or yohimbine in female patients [48]. "
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    ABSTRACT: Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered "ideal." As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.
    Depression research and treatment 02/2013; 2013(2):256841. DOI:10.1155/2013/256841
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    • "There are some reports on the use of PDE5-inhibitors for the treatment of depression associated sexual dysfunction. Nurnberg and colleagues found that a reduction in sexual difficulties (specifically delayed orgasm responses and inadequate lubrication ) in 98 previously sexually functioning women taking serotonin reuptake inhibitors, was associated with sildenafil treatment, while the women were continuing antidepressant treatment [Nurnberg et al. 2008]. Increased sildenafil dose for the treatment of depression associated SD in men is recommended [Nurnberg and Siegel, 2006; Seidman et al. 2003]. "
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    ABSTRACT: Nonmotor symptoms, among them sexual dysfunction, are common and underrecognized in patients with Parkinson disease; they play a major role in the deterioration of quality of life of patients and their partners. Loss of desire and dissatisfaction with their sexual life is encountered in both genders. Hypersexuality (HS), erectile dysfunction and problems with ejaculation are found in male patients, and loss of lubrication and involuntary urination during sex are found in female patients. Tremor, hypomimia, muscle rigidity, bradykinesia, 'clumsiness' in fine motor control, dyskinesias, hypersalivation and sweating may interfere with sexual function. Optimal dopaminergic treatment should facilitate sexual encounters of the couple. Appropriate counselling diminishes some of the problems (reluctance to engage in sex, problems with ejaculation, lubrication and urinary incontinence). Treatment of erectile dysfunction with sildenafil and apomorphine is evidence based. HS or compulsive sexual behaviour are side effects of dopaminergic therapy, particularly by dopaminergic agonists, and should be treated primarily by diminishing their dose. Neurologists should actively investigate sexual dysfunction in their Parkinsonian patients and offer treatment, optimally within a multidisciplinary team, where a dedicated professional would deal with sexual counselling.
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