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Tolerance to the Therapeutic Effect of Tadalafil Does Not Occur During 6 Months of Treatment: A Randomized, Double-Blind, Placebo-Controlled Study in Men with Erectile Dysfunction


Chris G. McMahon, Australian Centre for Sexual Health Suite 1-4, 1a Berry Road, St. Leonards, New South Wales 2065, Australia. Tel: (02) 9437-3906; Fax: (02) 9906-5900; E-mail:


Introduction.  Tolerance can cause a decrease in drug efficacy during chronic therapy, possibly leading to treatment failures.

Aim.  The aim of this article is to determine whether tolerance developed to the effects of tadalafil on erectile function (EF) over a 6-month treatment period.

Methods and Main Outcome Measures.  Post hoc analysis of data from a multicenter, double-blind, randomized, placebo-controlled, parallel group study was performed. Men (≥18 years of age) with erectile dysfunction (ED) were randomized to treatment with placebo (N = 47) or 20-mg tadalafil (N = 93) taken as needed for 6 months. This report focuses on efficacy assessed with the Sexual Encounter Profile (SEP) diary (diaries were collected after a 4-week treatment-free run-in period [baseline], and monthly for 6 months), and with the International Index of Erectile Function (IIEF) (administered at baseline, and at 3 and 6 months).

Results.  The mean per-patient percentage “yes” response on SEP question 3 (SEP3, successful intercourse) was 33 ± 4% at baseline, 74 ± 4% after 1 month, and 78 ± 4% after 6 months of tadalafil treatment. The IIEF EF domain score was 16.2 ± 0.7 at baseline, 24.3 ± 0.8 after 3 months, and 24.3 ± 0.9 after 6 months of tadalafil treatment. In a subgroup of patients who took tadalafil ≥3 times per week (N = 24), the SEP3 score was 87 ± 4% after 1 month and 93 ± 3% after 6 months of treatment, and the IIEF EF domain score was 27.3 ± 0.9 after 3 months and 28.5 ± 0.4 after 6 months. Of 16 tadalafil-treated patients who discontinued, three cited a lack of efficacy.

Conclusions.  Tadalafil treatment significantly improved SEP3 and IIEF EF domain scores. The efficacy of tadalafil, taken as needed, was maintained over a 6-month treatment period in men with ED. McMahon CG, Carson CC, Fischer CJ, Wang WC, Florio VA, and Bradley JD. Tolerance to the therapeutic effect of tadalafil does not occur during 6 months of treatment: A randomized, double-blind, placebo-controlled study in men with erectile dysfunction. J Sex Med 2006;3:504–511.