Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sildenafil citrate (Viagra) is a phosphodiesterase type V inhibitor used to treat erectile dysfunction. Ten men with idiopathic Parkinson's disease (PD) and erectile dysfunction were prescribed 50-100 mg sildenafil citrate to use in eight sexual encounters over a 2-month period. Patients underwent Unified Parkinson's Disease Rating Scale (UPDRS) evaluations and completed a Beck's Depression Inventory (BDI) and a Sexual Health Inventory-M version (SHI-M) at baseline and after 8 weeks. There was statistically significant improvement in total SHI-M scores (23.8 +/- 2.0 vs 16.6 +/- 2.8; p = 0.01), overall sexual satisfaction (p = 0.03), satisfaction with sexual desire (p = 0.04), ability to achieve erection (p = 0.02), ability to maintain erection (p = 0.03), and ability to reach orgasm (p = 0.04) with use of sildenafil citrate. UPDRS and BDI scores were not significantly changed. Side effects included headache in one patient during three sexual encounters. In this open-label study, sildenafil citrate significantly improved sexual function in men with PD and erectile dysfunction.
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PMID:Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson's disease. 1075 81

In the three years since its launch, sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been prescribed to more than 10 million patients worldwide and has been further evaluated in clinical studies in diverse patient populations. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled trials in patients with ED and underlying diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. Promising results have also been reported for patients with treated prostate cancer, end-stage renal failure, Parkinson's disease, and spina bifida and in multiple organ transplant recipients. Accounts of sildenafil use in clinical practice and postmarketing data reflect clinical trial findings of effectiveness in a broad spectrum of ED aetiologies and overall good tolerability. As in the clinical trials, most adverse events associated with sildenafil use have been transient, mild or moderate effects that rarely lead to treatment discontinuation.
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PMID:Three-year update of sildenafil citrate (Viagra) efficacy and safety. 1132 62

Impotence is often associated with protease inhibitor use, but much of the medical press ignored this issue until Spanish doctors described sexual difficulties following protease inhibitor therapy in 14 of 260 patients. Causes of sexual dysfunction in HIV-infected men are difficult to isolate but may also be traced to depression, physical weakness, opportunistic infections, stress, nerve damage, or hormonal imbalances. Pfizer, the manufacturer of Viagra, released study data on the effects of the drug used in combination with Ritonavir and Saquinavir; the data led Pfizer to alter Viagra dosing recommendations for people on protease inhibitors.
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PMID:Protease inhibitors, sexual dysfunction and Viagra. 1136 2

Erectile dysfunction (ED) and depression are highly prevalent conditions and frequently occur concomitantly in predisposed individuals. Men with ED and depression are also likely to have other comorbid conditions, including diabetes, hypertension, and heart disease. Because ED is also a common adverse effect of some medications for these conditions, patients are frequently noncompliant with treatment. Sildenafil citrate (Viagra) is effective in treating ED of a broad range of etiologies, suggesting that it may be equally beneficial in patients with ED that is associated with depressive symptoms and in those with ED resulting from serotonergic reuptake inhibitor (SRI) antidepressant treatment. We review the results of 3 randomized, placebo-controlled trials and a retrospective analysis of data pooled from 10 clinical trials that examine the efficacy of sildenafil in treating ED associated with depression and as an adverse effect of SRI treatment. The results suggest that sildenafil is efficacious as a first-line treatment for ED in men with untreated minor depression, in men with ED that is refractory to successful SRI treatment of depression, and in those whose depression was successfully treated but who developed ED as a consequence of SRI treatment. Given the complex interrelations among ED, depression, and other comorbid conditions, the key to proper management is a comprehensive evaluation, including sexual function, and an accurate differential diagnosis.
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PMID:Depression, antidepressant therapies, and erectile dysfunction: clinical trials of sildenafil citrate (Viagra) in treated and untreated patients with depression. 1241 34

Sildenafil citrate (Viagra) is a potent orally active cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor that is effective as a peripheral conditioner in the treatment of male erectile dysfunction (ED) of organic, psychogenic or mixed aetiology. Sildenafil is the first effective oral agent in the management of ED that has had a revolutionary impact on management of ED. The present review has been subdivided into five major sections. Based on the most recent peer-reviewed publications, the first section is aimed at critically evaluating PDE5 selectivity as well as the pharmacokinetics and pharmacodynamics of the drug, mainly to assess the best doses for each group of patients (i.e. adult and elderly men). Effectiveness in a broad spectrum ED population is the subject of the second section of the review, principally reporting post-marketing company-independent results. Safety and tolerability are the key concerns of the third section, with a broad consideration of the most commonly reported adverse events. Special attention has been paid to the cardiovascular safety of the drug, chiefly outlining the positive and potentially protective cardiac effects of sildenafil. Moreover, the impact of sildenafil in special patient populations is considered, namely in men complaining of diabetes mellitus, depression, neurological disorders, renal failure and those who have undergone a radical prostatectomy. Sildenafil and the ageing male has been especially underlined. Finally, the review covers a few new potential applications of sildenafil in ED patients with regard to high-dose treatment and combination therapy. The review ends with several considerations regarding the direct and/or indirect impact of sildenafil over quality of life and quality of partnership.
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PMID:Sildenafil in erectile dysfunction: a critical review. 1284 17

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
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PMID:Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. 1295 49

The objective of this study was to compare the economic cost of adding sildenafil citrate (Viagra, Pfizer Inc., New York, NY) to treat selective serotonin reuptake inhibitor (SSRI)-induced erectile dysfunction with that of discontinuing antidepressant pharmacotherapy, switching patients to another SSRI, or adding a non-SSRI. Based on our real-world experience in an academic medical center, we performed an economic analysis of a hypothetical cohort of 1000 patients taking SSRIs on a course of acute and continuation treatment recommended by the American Psychiatric Association. We used standard costing of antidepressants, sildenafil, and unit costs for physician visits within a managed care environment and cost-of-illness methodology to calculate the annualized cost of depression for different treatment outcomes. After 6 months of SSRI treatment, the sildenafil add-on group had the lowest cost estimates compared with groups that discontinued SSRIs, substituted another SSRI (switching), or added a non-SSRI to the existing SSRI (augmentation). Sensitivity analyses demonstrated that the physician visit was the single most important cost component in this hypothetical population and relapse/remission the most costly outcome. Sildenafil can be a cost-effective add-on therapy to control SSRI-induced erectile dysfunction. Healthcare payors should consider this when developing optimum treatment strategies for men with depression.
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PMID:Economic analysis of sildenafil citrate (Viagra) add-on to treat erectile dysfunction associated with selective serotonin reuptake inhibitor use. 1470 90

More than 30 million men are estimated to have erectile dysfunction (ED) in the United States. Worldwide, ED is estimated to affect more than 150 million men, and that number is expected to exceed 300 million men by the year 2025. The prevalence of ED ranges from 7% in men aged 18-29 years to 85% in men aged 76-85 years. In addition, a recent report showed that 68% of patients with ED aged 18 years and older have at least one comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression, and research suggests that ED may be an early indicator of systemic vascular disease. Viagra (sildenafil citrate), the first-in-class phosphodiesterase type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED. In the 7 years since its market launch, more than 750,000 physicians have prescribed sildenafil to more than 23 million men, helping establish an excellent safety and efficacy record. Clinical studies have demonstrated that sildenafil successfully treats ED of varied organic, psychogenic or mixed aetiology, and is effective in men with ED and comorbidities such as hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a breakthrough medication that addressed a previously unfulfilled medical need. The impact of sildenafil has stimulated academic, clinical and industrial research to better understand the nature of sexual function and develop better treatment and management for sexual dysfunctions such as ED. With the advent of other erectogenic therapies for the treatment of ED, this 7-year update will focus on the unique history and development of sildenafil, its current use and applications and its future directions and indications. Special emphasis is placed on the impact of sildenafil on our understanding of sexual health and on the extensive safety and efficacy data that have been amassed from numerous clinical trials.
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PMID:Past, present, and future: a 7-year update of Viagra (sildenafil citrate). 1592 97

Sexual dysfunction is a common and troublesome side effect associated with selective serotonin reuptake inhibitors and other antidepressants that reportedly occurs in 40%-70% of patients prescribed selective serotonin reuptake inhibitors. Management of this iatrogenic condition has relied on "clinical wisdom" derived over decades primarily from open-label, non-placebo-controlled, selected case and literature review studies. Management approaches fall into four broad categories: 1) antidote, 2) avoidance, 3) augmentation/switching, and 4) adaptation. Until the development of sildenafil (Viagra), none of the existing managements demonstrated clear efficacy in systematic, double-blind, placebo-controlled trials. Renewed interest in treatment-associated sexual dysfunction emerged because of advances in our knowledge of the biological mechanisms of sexual functioning, awareness that sexual dysfunction compromises patient adherence to treatment, and an improved focus on improving disease management outcomes of depression. Recent placebo-controlled studies provide evidence for questioning the effectiveness of earlier approaches to the management of sexual dysfunction side effects, and suggest improved treatment options with sildenafil. Effective management of treatment-emergent sexual dysfunction is a medical necessity in order to prevent relapse and recurrence of serious disorders such as major depression, which are highly treatment responsive but frequently compromised by medication noncompliance due to side effects such as sexual dysfunction.
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PMID:Managing treatment-emergent sexual dysfunction associated with serotonergic antidepressants: before and after sildenafil. 1599 May 10

Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p </= 0.001). No changes in sexual functioning were detected. Significant improvement was also noted on the self-report measures of depressive symptoms. Sildenafil citrate might have an antidepressant effect on late onset DD, that is not attributable to improvement in erectile function. Possible explanations for this effect are offered. Larger placebo controlled studies are warranted.
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PMID:An open-label pilot study to evaluate the efficacy of sildenafil citrate in middle-aged men with late-onset dysthymia. 1855 28


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