Psychosocial Outcomes After Tadalafil or Sildenafil for ED
Psychosocial Outcomes After Tadalafil or Sildenafil for ED
Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N=252) or sildenafil-citrate (sildenafil) 50 mg PRN (N=261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P=0.044 and P=0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups.
The most widely prescribed PDE5Is approved for the treatment of ED are sildenafil-citrate (sildenafil), tadalafil and vardenafil. Although PDE5Is are generally well tolerated and effective, patients poorly adhere to treatment in real-life conditions. We recently reported the primary outcome of a randomized, open-label study showing that men with ED who started initial PDE5I treatment with tadalafil once-a-day (OaD) or on demand (pro-re-nata, PRN) adhered to randomized treatment significantly longer than men initiating treatment with sildenafil PRN. Improvement of erectile function (EF) was not significantly different between treatment groups (assessed by International Index of Erectile Function—Erectile Function (IIEF-EF) and % 'yes'-responses to Sexual Encounter Profile (SEP) Question 3 (successful intercourse). The most frequent reason for discontinuation from randomized treatment without significant difference between groups was 'lack of efficacy (hardness of erection)'. An important reason for switching to a different treatment in all groups was preference for a dosing scheme (PRN or OaD) different from the randomized regimen. Reasons for discontinuation of randomized treatment with significant differences between treatment groups included 'lack of efficacy (duration of action)' and 'time constraints due to short window of action', and the patients' feeling that medication was controlling their sexual life. Several of these reasons indicate a clinical relevance of the long half-life of tadalafil (17.5 vs 3.7 h for sildenafil). EF improvements can last up to 36 h post-dose for tadalafil PRN, compared with up to 12 h for sildenafil. The unique pharmacokinetic properties of tadalafil allow for OaD dosing, which results in continuous PDE5 inhibition sufficient for ED treatment in the majority of patients.
However, EF improvement is not the only factor that is crucial to resuming a satisfying sex life. In addition to general concerns regarding efficacy or tolerability and patient or partner preference for a particular dosing scheme, psychosocial outcomes such as sexual self-confidence and spontaneity, in part related to the effect of time constraints on sexual activity, may have an important role and may be particularly relevant for men without previous PDE5I experience starting ED treatment. We additionally evaluated the impact of initiating treatment with tadalafil OaD, tadalafil PRN and sildenafil PRN on all IIEF domains, improvement of erections and ability to engage in sexual activity, sexual self-confidence, spontaneity and other psychosocial outcomes, and assessed overall treatment satisfaction in men with ED with no previous PDE5I treatment.
Abstract and Introduction
Abstract
Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N=252) or sildenafil-citrate (sildenafil) 50 mg PRN (N=261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P=0.044 and P=0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups.
Introduction
The most widely prescribed PDE5Is approved for the treatment of ED are sildenafil-citrate (sildenafil), tadalafil and vardenafil. Although PDE5Is are generally well tolerated and effective, patients poorly adhere to treatment in real-life conditions. We recently reported the primary outcome of a randomized, open-label study showing that men with ED who started initial PDE5I treatment with tadalafil once-a-day (OaD) or on demand (pro-re-nata, PRN) adhered to randomized treatment significantly longer than men initiating treatment with sildenafil PRN. Improvement of erectile function (EF) was not significantly different between treatment groups (assessed by International Index of Erectile Function—Erectile Function (IIEF-EF) and % 'yes'-responses to Sexual Encounter Profile (SEP) Question 3 (successful intercourse). The most frequent reason for discontinuation from randomized treatment without significant difference between groups was 'lack of efficacy (hardness of erection)'. An important reason for switching to a different treatment in all groups was preference for a dosing scheme (PRN or OaD) different from the randomized regimen. Reasons for discontinuation of randomized treatment with significant differences between treatment groups included 'lack of efficacy (duration of action)' and 'time constraints due to short window of action', and the patients' feeling that medication was controlling their sexual life. Several of these reasons indicate a clinical relevance of the long half-life of tadalafil (17.5 vs 3.7 h for sildenafil). EF improvements can last up to 36 h post-dose for tadalafil PRN, compared with up to 12 h for sildenafil. The unique pharmacokinetic properties of tadalafil allow for OaD dosing, which results in continuous PDE5 inhibition sufficient for ED treatment in the majority of patients.
However, EF improvement is not the only factor that is crucial to resuming a satisfying sex life. In addition to general concerns regarding efficacy or tolerability and patient or partner preference for a particular dosing scheme, psychosocial outcomes such as sexual self-confidence and spontaneity, in part related to the effect of time constraints on sexual activity, may have an important role and may be particularly relevant for men without previous PDE5I experience starting ED treatment. We additionally evaluated the impact of initiating treatment with tadalafil OaD, tadalafil PRN and sildenafil PRN on all IIEF domains, improvement of erections and ability to engage in sexual activity, sexual self-confidence, spontaneity and other psychosocial outcomes, and assessed overall treatment satisfaction in men with ED with no previous PDE5I treatment.
