Paula L. Hensley

Sildenafil Treatment of Women With Antidepressant-Associated Sexual Dysfunction: A Randomized Controlled Trial

CONTEXT 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. OBJECTIVE To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION 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. MAIN OUTCOME MEASURES 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. RESULTS 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. CONCLUSION In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00375297.

Escitalopram: an open-label study of bereavement-related depression and grief.

BACKGROUND Approximately 8 million Americans suffer the loss of an immediate family member each year. Chronic depression may develop following bereavement-about 15% of the bereaved are depressed at 1 year. Several studies of psychotropic medications have demonstrated improvement in depression ratings, but little data exists for selective serotonin reuptake inhibitor treatment in bereavement-related depression. METHODS Thirty adults were treated with escitalopram for 12 weeks in open fashion for a major depressive episode following loss of a close family member (parent, sibling, child, or spouse/significant other). Main outcome measures were the Hamilton Depression Rating Scale, the Montgomery-Asberg Rating Scale, the Texas Revised Inventory of Grief, and the Inventory of Complicated Grief. RESULTS Twenty-nine of thirty participants returned for at least one set of efficacy measures after starting medication. Nineteen subjects (66%) experienced a 50% or greater improvement on the Hamilton Depression Scale. Fifteen subjects (52%) achieved remission, defined as a final score of 7 or less on the Hamilton Depression Scale. Escitalopram significantly reduced depressive symptoms (P<0.001) over time. Subjects with uncomplicated grief and those with complicated grief improved similarly over time. Subjects with and without PTSD improved to a similar degree. Escitalopram was well tolerated. LIMITATIONS Open-label design, psychotherapy was not controlled, relatively short treatment period, variation in grief scales make comparisons to other studies difficult, all subjects with complicated grief also were clinically depressed, and gender discrepancy of sample. CONCLUSIONS Escitalopram improved depressive, anxiety, and grief symptoms in individuals experiencing a major depressive episode related to the loss of a loved one.

Sildenafil in the treatment of sexual dysfunction induced by selective serotonin reuptake inhibitors : An overview

This review discusses the potential role of sildenafil in managing antidepressant-induced sexual dysfunction, with a focus on that associated with selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). To provide a context, the epidemiology, assessment, prevalence with comparative agents and management strategies for SSRI/antidepressant-induced sexual dysfunction are reviewed.Sexual dysfunction is a frequent adverse effect of many therapeutic agents; it is prominently associated with SSRIs, and may be an important factor contributing to discontinuation of and noncompliance with antidepressants. However, a significant number of patients spontaneously develop tolerance to this reversible adverse effect over time.Sildenafil is an important addition to the therapeutic armamentarium for treating erectile dysfunction in men. Preliminary data suggest that it also has potential for treating antidepressant-induced sexual dysfunction in men and women, particularly in patients who do not have sexual dysfunction prior to becoming ill. The effective management of SSRI treatment emergent sexual dysfunction can have an important impact on improving the effectiveness and clinical outcomes of treatment by reducing switching and premature discontinuation of medication, and reducing the related morbidity/mortality of major depression and other disorders for which these drugs are prescribed.

SSRI sexual dysfunction: a female perspective.

Women experience two to three times the rate of depression that men do. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for many conditions other than depression, such as anxiety disorders, premenstrual dysphoric disorder, pain syndromes, impulse control disorders, and personality disorders, some of which are more common in women. Increasing awareness of sexual side effects has tempered the initial enthusiasm with which SSRIs were greeted. Men taking SSRIs report higher rates of sexual side effect than women taking them, however, women seem to experience more severe sexual dysfunction. In this article, we discuss the epidemiology of sexual dysfunction and describe treatments with sildenafil.

Formulary restriction of selective serotonin reuptake inhibitors for depression: potential pitfalls.

The American healthcare market is currently estimated at more than

Treatment of Antidepressant-Associated Sexual Dysfunction With Sildenafil: A Randomized Controlled Trial

US900 billion with double digit rising costs per year. Psychotropic agent costs have more than kept pace with market increases. Medication acquisition costs are an obvious focus for limiting costs in various care systems.Restrictive formularies are a common method of attempting to limit costs. To support our opinion that a single agent is ill advised, we explored the available evidence on the intended and unintended consequences of having a single or exclusive selective serotonin reuptake inhibitor (SSRI) on a formulary. Central to this position is an assumption of the interchangeability of SSRIs; we examined the evidence for and against this through a model to determine the probability of interchangeability. We conclude that the practice of having a single SSRI on the formulary for a healthcare plan seems ill founded. Patients who switch antidepressants remain in treatment 50% longer and cost approximately 50% more to treat in a more costly treatment setting.Giving the primary care physician several antidepressant choices can provide more options to continue treatment of his or her patient in the less expensive primary care setting. In terms of cost containment, formulary restrictions are far more likely to have the opposite effect.