© 2009 THE AUTHORS 376 JOURNAL COMPILATION © 2 0 0 9 B J U I N T E R N A T I O N A L | 1 0 4 , 3 7 6 – 3 8 3 | doi:10.1111/j.1464-410X.2009.08560.x 2009 The Authors; Journal compilation 2009 BJU International Original Article SILDENAFIL IN PTSD-EMERGENT ED SAFARINEJAD et al. Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat-related post-traumatic stress disorder: a double-blind, randomized and placebo-controlled study Mohammad Reza Safarinejad, Ali Asgar Kolahi* and Gholamhossein Ghaedi † Urology and Nephrology Research Centre, *Department of Health and Community Medicine, Shahid Beheshti University Research Centre (MC) and † Department of Psychiatry, Faculty of Medicine, Shahed University, Tehran, Iran Accepted for publication 21 November 2008 hypertension, Peyronie’s disease) and smokers of more than five cigarettes daily were excluded. The patients were randomly divided into a group of 133 who received 100 mg of on-demand sildenafil 0.75–2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use ≥ 16 doses or attempts at home. The efficacy of the treatments was assessed every four attempts during treatment, and at the end of the study, using responses to the 15- question International Index of Erectile Function (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, patients’ event logs of sexual activity, and a Global Assessment Question about erections. RESULTS Sildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures ( P = 0.08). A normal EF domain score ( ≥ 26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively ( P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo ( P = 0.08). The incidences of treatment-emergent adverse events were significantly greater in the sildenafil arm than in the placebo group ( P = 0.01). CONCLUSIONS Sildenafil is no better than placebo in treating PTSD-emergent ED. Further randomized clinical trials are warranted in combat veterans and other populations with PTSD to better elucidate the role of phosphodiesterase type 5 inhibitors in treating PTSD-emergent ED. KEYWORDS erectile dysfunction, post-traumatic stress disorder, sildenafil, treatment. Study Type – Therapy (RCT) Level of Evidence 1b OBJECTIVE To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat- related post-traumatic stress disorder (PTSD). PATIENTS AND METHODS In all, 266 combat-exposed war veterans with ED (aged 37–59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician-Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. Patients with comorbid conditions (diabetes mellitus, hypercholesterolaemia, INTRODUCTION Post-traumatic stress disorder (PTSD) was first recognized after the devastating effects that war experiences had on soldiers serving in Vietnam. Of Vietnam veterans, ≈ 30% developed PTSD during, or at some point after, the Vietnam War [1]. PTSD is listed as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM)- IV [2]. The symptoms of PTSD fall into three domains and define PTSD: re-experiencing symptoms, avoidance symptoms, and hyper- arousal symptoms (DSM IV TR) [3]. It has been shown that veterans with chronic PTSD have emotional, social and professional problems [4]. PTSD also results both significant intrapersonal and interpersonal difficulties, including problems with family cohesion, sexual intimacy, and the expression of affection, hostility and aggression [5,6]. The symptoms of PTSD and comorbid conditions among the veterans of wars typically last for more than two decades [7]. There has been very limited investigation of the prevalence of sexual dysfunction (SD) in patients with PTSD. Vietnam combat veterans with PTSD were more likely to report ‘low sexual desire’ than were subjects without PTSD [8]. Letourneau et al. [9] reported that > 80% of combat veterans with PTSD experience SD, of whom 69% have erectile dysfunction (ED). The problems of patients with PTSD have a BJUI BJU INTERNATIONAL