sildenafil-citrate and Stress-Disorders--Post-Traumatic

To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat-related post-traumatic stress disorder (PTSD).. 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, 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 > or =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.. 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 (> or =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).. 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.

Topics: Adult; Analysis of Variance; Combat Disorders; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Stress Disorders, Post-Traumatic; Sulfones; Treatment Outcome

Post-traumatic Stress Disorder (PTSD) symptoms cause dysfunction in broad areas of patients' lives and those of their families. Sexual dysfunction (SD) is common in these patients and aggravates their distress, affecting overall sexual activity, desire, arousal, orgasm, activity and satisfaction. PTSD clinic patients are frequently referred for consultation and treatment in the SD clinic. This prospective naturalistic follow-up study of a random group of patients was intended to evaluate response to pharmacologic and psychotherapeutic interventions for SD, in terms of both sexual functioning and overall symptomatology.. Ten patients fulfilling DSM-IV diagnostic criteria for PTSD (one woman and nine men) were recruited. Treatment for the sexual symptoms was tailored individually and was administered in addition to the continuing (stable) treatment in the PTSD clinic.. After two months of treatment for the sexual symptoms, statistically significant improvements in all domains of sexual functioning were observed. In parallel, statistically significant improvements in all domains of the Impact of Events Scale scores were observed, both on the avoidance and intrusive subscales. There were no significant differences in response to treatment in terms of time elapsed since the onset of PTSD, or the pattern or severity of sexual and PTSD symptoms.. The results of this modest study demonstrate the importance of relating to the SD of PTSD patients irrespective of the duration or severity of their disorder. In this mixed group of PTSD patients with varied duration of symptoms, both SD and PTSD core symptoms improved significantly in response to individually tailored adjunctive treatment of the SD.

Topics: Adult; Chronic Disease; Combined Modality Therapy; Complementary Therapies; Female; Humans; Male; Middle Aged; Piperazines; Prospective Studies; Psychotherapy; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Stress Disorders, Post-Traumatic; Sulfones; Surveys and Questionnaires; Vasodilator Agents

Post Traumatic Stress Disorder (PTSD) is known to be associated with Erectile Dysfunction (ED). Sildenafil citrate was shown to be effective treatment for ED among different clinical populations. However, to date, no placebo-controlled trial has assessed sildenafil's effectiveness for treating ED in PTSD patients. The goal of the present study was to address this question using a double-blind placebo controlled crossover design.. A four-week double-blind crossover trial of sildenafil (50 mg up to 100 mg per usage) versus placebo was conducted on 21 outpatients diagnosed with chronic PTSD accompanied by ED. Erectile function was assessed biweekly using the International Inventory of Erectile Function (IIEF). Depressive symptoms, PTSD symptoms and subjective well-being scores were assessed as well.. Analysis of IIEF scores revealed a main effect of treatment phase (E = 33.361, df =2, P < 0.000). Pairwise comparisons showed that sildenafil IIEF scores (mean = 45.19 +/- 15.05) were significantly higher compared to baseline scores (mean = 20.00 +/- 12.32, P = 0.000) and placebo scores (mean = 33.04 +/- 12.99). Compared to placebo, a significant improvement was also observed during the sildenafil phase in erectile function, orgasmic function and sexual desire. There was no significant change in depression, PTSD symptoms or subjective well-being.. The results of this study suggest that sildenafil citrate treatment for ED in PTSD patients was accompanied with improvement of ED symptoms and was found to be significantly better than placebo. Nevertheless, this effect should be considered marginal since patients still meet the criteria of ED after treatment. Larger, parallel group studies are warranted.

Topics: Adolescent; Adult; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Satisfaction; Penile Erection; Piperazines; Purines; Sexuality; Sildenafil Citrate; Stress Disorders, Post-Traumatic; Sulfones; Surveys and Questionnaires; Treatment Outcome

Post-traumatic stress disorder (PTSD) may be associated with shrinkage of the hippocampus, with glutamate release causally related to these events. Recent animal studies strongly implicate activation of the nitric oxide (NO)-cascade in anxiety and stress. Using an animal model of repeated trauma, the effect of stress was investigated on the hippocampal NO-cGMP signalling pathway, specifically the release of nitrogen oxides (NOx) and its modulation by NMDA receptor-, NO-, cGMP- and nuclear factor K-beta (NFK-beta)-selective drugs. Immediately after stress, rats received the glutamate NMDA receptor antagonist, memantine (MEM; 5 mg/kg i.p./d), the NO synthase inhibitor, 7-nitroindazole sodium salt (7-NINA; 20 mg/kg i.p./d), the cGMP-specific PDE inhibitor, sildenafil (SIL; 10 mg/kg i.p./d) or the NFkappa-beta antagonist, pyrollidine dithiocarbamate (PDTC; 70 mg/kg i.p./d), for 7 days. Stress significantly increased hippocampal NOx on day 7 post-stress, which was blocked by either 7-NINA or PDTC, while MEM was without effect. SIL, however, significantly augmented stress-induced NOx accumulation. Increased cGMP therefore acts as a protagonist in driving stress-related events, while both nNOS (neuronal NOS) and iNOS (inducible/immunological NOS) may represent a therapeutic target in preventing the effects of severe stress. The value of NMDA receptor antagonism, however, appears limited in this model.

Topics: Animals; Cyclic GMP; Disease Models, Animal; Hippocampus; Indazoles; Male; NF-kappa B; Nitric Oxide; Piperazines; Proline; Purines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sildenafil Citrate; Stress Disorders, Post-Traumatic; Sulfones; Thiocarbamates