Overview of Trials

The trials evaluated the following treatments: phentolamine (one additional trial of phentolamine is described in the Sildenafilsection¹²⁴), ^{333, 338} trazodone, ^{336, 337, 339, 341, 344} cabergoline, ^{162, 350} pentoxifyling (in 4 reports), ^{340, 343, 345, 349} and miscellaneous medications. The latter consisted of treatments with moclobemide, ³³⁴ isoxsuprine, ³³⁵ opiate antag, ³⁴² ACE, ³⁴⁶moxonidine, ³⁴⁷ dehydropiand, ³⁴⁸ tetrahydrobiopterin (BH4), ³⁵³ Myoinositol, ³⁵¹ and Tianeptine.³⁵² (Table F-10, Appendix F)

Phentolamine. Two trials investigated the effect of phentolamine in comparison to placebo.^{333, 338} One of the trials was used a crossover design (n = 5)³³³ and the other a parallel design (n = 44).³³⁸ Subjects in these trials were generally older than 18 years, with ED of at least 3 months of duration and various etiologies (the majority with organic causes). Total Jadad score was 3 for both trials.^{333, 338} The allocation concealment was unclear for both trials. The trial outcomes were patient diary³³⁸ and RigiScan measures on nocturnal erectile activity.³³³

Harms. One trial reported one adverse event occurring in a patient taking 60 mg dose.³³⁸ In another trial, no adverse events occurred.³³³ No serious adverse events were reported in any of these trials.

Efficacy. Forty to 50 percent of patients improved their erections with higher doses of phentolamine (40 and 60 mg) compared with 30 and 20 percent with lower dose (20 mg) or placebo respectively.³³⁸

Oral phentolamine (40 mg, 3 consecutive nights) administered before sleep increased the number of erectile events with rigidity of at least 60 percent lasting at least 10 minutes (p = 0.02), and the rigidity activity unit (RAU) per hour of sleep both at the base (p = 0.023) and the tip of the penis (p = 0.019), which were not different from changes after administration of placebo.³³³

Trazodone versus other active treatment versus placebo. Five trials reported on the effect of treatment with trazodone (n = 333, range: 34–100 participants).^{336, 337, 339, 341, 344} The trials were conducted in Belgium, ³³⁶ Turkey, ^{341, 344} the Netherlands, ³³⁹and US.³³⁷ Total Jadad score ranged from 1³⁴¹ to 4³³⁹ with a mean of 2.8.

Four studies used a parallel^{336, 339, 341, 344}, and one crossover design.³³⁷ Trazodone was administered at doses of 50 mg, ^{337, 344}150 mg, ^{339, 341} or 200 mg³³⁶ per day. Aydin et al. (1995)³⁴¹ compared the effect of trazodone to oral testosterone (120 mg/d), hypnosis or placebo. Kurt et al. (1994) compared trazodone to ketanserin and mianserin (antiserotoninergic agents).³⁴⁴ Subjective measures such as self reported questionnaires to address improvement in erection with treatment were used in four trials.^{336, 337, 341, 344} The outcomes based on RigiScan measurements (i.e. NTP, rigidity) were reported in two trials.^{336, 339}

Harms. In one trial, numerically more patients in the trazodone group reported dry mouth (25.0 percent), drowsiness (18.8 percent), and fatigue (14.6 percent) compared with the placebo group (16.7, 12.5, and 8.3 percent, respectively).³³⁷ Another study reported 50 percent more withdrawals due to adverse events in trazodone group versus the placebo group.³³⁹ In the trazodone arm of one trail, five patients experienced sedations; no information on adverse events for other groups (i.e., testosterone, hypnosis, and placebo) was reported. ³³⁹ In a trial comparing the efficacy and harms of trazodone to mianserin, ³⁴⁴ two patients (8 percent) withdrew due to adverse events from the mianserin treatment group and two patients (8 percent) in the trazodone group developed serious adverse events (priapism and sedation).

Efficacy. Improvement in erection measured by Index of Sexual Satisfaction was 19 and 24 percent in trazodone and placebo groups, respectively.³³⁷ One study reported minor improvement from baseline in trazodone group but the between-group (versus placebo) difference for base rigidity (> 60 percent), nocturnal erection, or morning erection, was not statistically significant.³³⁶ For one trial, improved erections were observed in 66, 60, 80, and 39 percent of the patients treated with trazodone, testosterone, hypnosis, and placebo, respectively.³⁴¹

The proportions of patients with positive response (3 or more successful intercourse attempts during 30 days and rigidity ≥ 30 minutes) at the end of 30 days of treatment with 50 mg trazodone, 20 mg ketanserin, 10 mg mianserin, and placebo were 65.2, 19.1, 31.6, 13.6 percent, respectively.³⁴⁴

Cabergoline versus placebo. Two trials were identified with a total of 452 participants randomly assigned to treatment with cabergoline (n = 225) or placebo (n = 222).^{162, 350} The trials were conducted in Germany³⁵⁰ and Iran.¹⁶² The German study recruited patients with no organic cause of ED. The Iranian study recruited non-responders to previous sildenafil therapy. The mean age of participants was approximately 40 years. Total Jadad scores for the two trials were 3³⁵⁰ and 5.¹⁶² The allocation concealment was unclear in one³⁵⁰ and adequate in the other.¹⁶² Both studies were parallel design and placebo controlled. The dose of cabergoline was 0.5 mg per day³⁵⁰ or 0.5–1 mg.¹⁶² In both trials, the IIEF was used to measure baseline severity and treatment effect.

Harms. The number of patients with any adverse events was greater in cabergoline group (12.2 percent versus 2.0 percent, p = 0.001).¹⁶² Withdrawals due to adverse events were higher in the active arm versus placebo in the study which reported this information (5.9 versus 1.01 percent).¹⁶² No information on serious adverse events was reported in any of these trials.

Efficacy. Both trials reported numerically or statistically significant improvements in the results with cabergoline 0.5 mg versus placebo. The German study reported a change of 11.7 in mean scores of erectile domain of IIEF from baseline in comparison to a change of 6.9 in the placebo group. In the Iranian trial, patients improved by 5 points in the Intercourse Satisfaction domain of the IIEF.¹⁶² The improvement in Q3 (frequency of penetration), and Q4 (ability to maintain the erection after sexual penetration) was 45.5 and 51.4 percent in the cabergoline arm versus 15 and 20 percent in the placebo arm, respectively.¹⁶²

Pentoxifylline. Three parallel design studies were included (n = 114, range 18–60).^{340, 343, 345} Mean age of participants was approximately 60.6 years. The trials were conducted in Turkey³⁴⁰ and US.^{343, 345} The trial duration ranged from 2 to 3 months.

Total Jadad score ranged from 1³⁴⁰ to 2.^{343, 345} Allocation concealment methods were unclear in all three studies.

All three trials were placebo controlled administering 1.2 g/day of pentoxifylline and evaluating subjective measures of improvement in erection. One study also included RigiScan outcomes (i.e., NPT, penile rigidity).³⁴³