Placebo and nocebo effects in randomized trials with phosphodiesteraze type 5 inhibitors
Article published in Urologia Polska 2005/58/2.
Jakub Dobruch, Andrzej Borówka, Artur A. Antoniewicz
- Oddział Urologii Międzyleskiego Szpitala Specjalistycznego w Warszawie
Ordynator oddziału: prof. dr hab. Andrzej Borówka
erectile dysfunction, phosphodiesteraze type 5 inhibitors, nocebo, placebo
- introduction and objectives
- Efficacy of phosphodiesteraze type 5 inhibitors in the treatment of erectile dysfunction has been proved in many randomized, placebo controlled trials. The purpose of the study was to evaluate the role of placebo and nocebo effects in randomized trials concerning treatment of erectile dysfunction with phosphodiesteraze type 5 inhibitors.
- material and methods
- Results of randomized, placebo controlled trials concerning efficacy and safety of phosphodiesteraze type 5 inhibitors (sildenafil, vardenafil and tadalafil) in the treatment of erectile dysfunction were analyzed. The placebo effect was estimated basing on the changes of International Index of Erectile Function (IIEF) and Global Assessment Questions (GAQ) symptoms scores. Placebo effect was presented as percent change of mentioned above indexes comparing final and initial values. Nature and frequency of observed adverse events and percentage of men who discontinued the study were also evaluated.
- Erectile function was improved in the placebo groups. Mean IIEF-5 questions 3 and 4 increased even by 50% and 44% respectively. The percentage of men who claimed that erectile function improved reached 37%. 0-81% of patients within the placebo groups discontinued the study. Adverse events were the reason of discontinuation in 0% to 2.6% cases.
- The placebo effect was observed in each study however its intensity varied among studies. It was less evident in men with proved organic etiology of erectile dysfunction.
- NIH Consensus Development Panel on Impotence. NIH consensus conference: impotence. JAMA 1993; 270; 83-90.
- Ignarro LJ, Bush PA, Buga GM et al: Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990; 170; 843-850.
- Lincoln TM: Cyclic GMP and mechanisms of vasodilation. Pharmacol Ther 1989; 41; 479-502.
- Stief CG, Uckert S, Becker AJ et al: The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol 1998; 159; 1390-1393.
- Rosen RC, Riley A, Wagner G et al: The International Index of Erectile Function (IIEF): a mulitidimensional scale for assessment of erectile dysfunction. Urol 1997; 49; 822-830.
- Dobruch J, Borówka A, Antoniewicz AA, Chłosta P: Efekt placebo i nocebo: istota i przyczyny. Urol Pol 2004; 57; 7-10.
- Fink HA, Mac Donald R, Rutks IR et al: Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Int Med 2002; 162; 1349-1360.
- Young JM, Bennett C, Gilhooly P et al: Efficacy and safety of sildenafil citrate (VIAGRA) in black and hispanic american men. Urol 2002; 60; 39-48.
- Nurnberg HG, Hensley PL, Gelenberg AJ et al: Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. JAMA 2003; 289; 56-64.
- Guliano F, Hultling C, El Masry WS et al: Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Sildenafil Study Group. Annals Neurol 1999; 46; 15-21.
- Maytom MC, Derry FA, Dinsmore WW et al: A two-part pilot study of sildenafil (VIAGRA) in men with erectile dysfunction caused by spinal cord injury. Spinal Cord 1999; 37; 110-116.
- Lue TF: A study of sildenafil (Viagra), a new oral agent for the treatment of male erectile dysfunction. J Urol 1997; 157; 181A.
- Montorsi F, McDermott TE, Morgan R et al: Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. Urol 1999; 53; 1011-1018.
- DeBusk RF, Pepine CJ, Glasser DB et al: Efficacy and safety of sildenafil citrate in men with erectile dysfunction with stable coronary artery disease. Am J Cardiol 2004; 93; 147-153.
- Incrocci L, Koper PCM, Hop WCJ, Slob KA: Sildenafil citrate (VIAGRA) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double blind, placebo controlled, cross-over study. Int J Radiation Oncology Biol Phys 2001; 51; 1190-1195.
- Dinsmore WW, Hodges M, Hargreaves C et al: Sildenafil (VIAGRA) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects. Urol 1999; 53; 800-805.
- Tan HM, Moh CL, Mendoza JB et al: Asian sildenafil efficacy and safety study (ASSESS-1): a double-blind, placebo-controlled, flexible-dose study of oral sildenafil in Malaysian, Singaporean, and Filipino men with erectile dysfunction. The Assess-1 Study Group. Urol 2000; 56; 635-640.
- Rendell MS, Raifer J, Wicker PA, Smith MD: Sildenafil for the treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. JAMA 1999; 281; 421-426.
- Meuleman E, Cuzin B, Opsomer RJ et al: A dose-escalation study to assess the efficacy and safety of sildenafil citrate in men with erectile dysfunction. BJU International 2001; 87; 75-81.
- Lewis R, Bennett CJ, Borkon WD et al: Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as determined by the Erectile Dysfunction Inventory of Treatment Satisfaction Questionnaire. Urol 2001; 57; 960-965.
- Padma-Nathan H, Steers WD, Wicker PA: Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. Int J Clin Practice 1998; 52; 375-379.
- Seidman SN, Roose SP, Menza MA et al: Treatment fo erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sidenafil citrate. Am J Psych 2001; 158; 1623-1630.
- Nurnberg GH, Gelenberg A, Hargreave TB et al: Eficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors. Am J Psych 2001; 158; 1926-1928.
- Goldstein IL, Tom F, Padma-Nathan H et al: Oral sildenafil in the treatment of erectile dysfunction. N Eng J Med 1998; 338; 1397-1404.
- Padma-Nathan H, Stecher VJ, Sweeney M et al: Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial. Urol 2003; 62; 400-403.
- Porst H, Young JM, Scmidt AC et al: International Vardenafil Stuudy Group: Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patients subgroups. Urol 2003; 62; 519-524.
- Brock G, Nehra A, Lipshultz LI et al: Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. J Urol 2003; 170; 1278-1283.
- Hatzichristou D, Montorsi F, Buvat J et al: European Vardenafil Study Group: The efficacy and safety of flexible-dose vardenafil (levitra) in a broad population of European men. Eur Urol 2004; 45; 634-641.
- Hellstrom WJG, Gittelman M, Karlin G et al: Vardenafil Study Group. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urol 2003; 61; 8-14.
- Porst H, Padma-Nathan H, Giuliano F et al: Efficacy of tadalafil for the treatment of erectile dysfunction AT 24 and 36 hours after dosing: a randomized controlled trial. Urol 2003; 62; 121-126.
- Stuckey BGA: Tadalafil Phase 3 experience. Eur Urol 2002; 1; 25-30.
- Seftel AD, Wilson SK, Knapp PM et al: The efficacy and safety of tadalafil in United States and Puerto Rican men with erectile dysfunction. J Urol 2004; 172; 652-657.
- Montorsi F, Nathan HP, McCullough A et al: Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. J Urol 2004; 172; 1036-1041.
- Brock GB, McMahon CG, Chen KK et al: Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002; 168; 1332-1336.
- Thadani U, Smith W, Nash S et al: The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol 2002; 40; 2006-2012.
- Dobruch J, Borówka A, Chłosta P, Antoniewicz AA: Znaczenie efektu placebo i efektu nocebo w badaniach nad skutecznością farmakologicznego leczenia chorych na łagodny rozrost stercza. Urol Pol 2004; 57;
- Benet AE, Meloman A: The epidemiology of erectile dysfunction. Urol Clin North Am 1995; 22; 699-709.
- Araujo AB, Durante R, Feldman HA et al: The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from Massachusetts Male Aging Study. Psychosom Med 1998; 60; 458-465.
Międzyleski Szpital Specjalistyczny
ul. Bursztynowa 2
tel. 0 503072230