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Apomorphine for erectile dysfunction

Clinical bottom line

Sublingual apomorphine is effective in erectile dysfunction. The number needed to treat compared with placebo for erections sufficient for intercourse was 7 (5 to 10). Nausea was the chief adverse effect.


Background

Apomorphine is a centrally acting, nonopioid, dopamine agonist. Such agents are known to cause erections in rats, and dopamine agonists improve erections in men treated for Parkinson's disease. The chief problem is nausea.

Searching

Searching was done using PubMed, Medline and the Cochrane Library, up to September 2005. Randomised trials in which apomorphine was compared with placebo or other treatments were sought. Details of the trials were abstracted and quality scoring done with a 5 point scale.

The outcome sought was patient/partner judgement of satisfactory erections suitable for intercourse, or actual intercourse, at home. Relative risk and NNT were calculated using standard methods. A list of references is given at the end of the article.

Results

The randomised comparative studies are shown in Table 1. Four studies compared sublingual apomorphine at various fixed or dose-optimised systems between 2 and 6 mg with placebo, in 1594 men. A successful outcome, usually as percentage of successful attempts at intercourse, occurred in 45% of men with apomorphine, compare with 29% of men with placebo (Figure 1). The relative risk was 1.4 (95% confidence interval 1.2 to 1.7), and the number needed to treat was 6.6 (5.0 to 9.6).

Table 1: Placebo and active controlled studies with apomorphine

Study
Design
Quality score
Patients
Treatment
Outcomes
Result
Adverse events
Dula et al, 2000
USA
Sublingual apomorphine
Randomised, double-blind, 8 week comparison of dose-optimised, and fixed dose apomorphine versus placebo R=1
DB=2
WD=1
Total=4
Established ED (mean 5 years), in otherwise good health, mean age 55 years, mostly white 1 Dose optimised, 2,4,5,6 mg (n=242)
2 Fixed dose 5 mg (n=119)
3 Fixed dose 6 mg (n=89)
4 Placebo (n=119)
Primary was percentage of attempts resulting in erection firm enough for intercourse 1 50%
2 51%
3 50%
4 33%
Similar results from partner
Increased rates of nausea, dizziness, sweating in maintenance period, though higher initially
Dula et al, 2001
USA
Sublingual apomorphine
Randomised, double-blind, crossover of 3 mg vs placebo and 3 mg vs 4 mg, each of 4 weeks R=1
DB=1
WD=0
Total=2
Established ED, 60% with co-morbidities, mean age 57 years 1 3 mg (n=194)
2 placebo (n=194)
3 3 mg (n=102)
4 4 mg (n=102)
two separate studies
Primary was percentage of attempts resulting in erection firm enough for intercourse 1 47%
2 32%
3 49%
4 50%
Similar results from partner
Better results in mild or moderate ED than severe ED
Increased rates of nausea, dizziness, yawning
von Keitz et al, 2002
Europe
Sublingual apomorphine
Randomised, double-blind comparison of dose-optimised apomorphine 2-4 mg versus placebo for 8 weeks R=1
DB=2
WD=1
Total=4
Established ED, 40% with co-morbidities, mean age 55 years, mostly white, with normal baseline testosterone 1 Dose optimised, 2-4 mg (n=254)
2 Placebo (n=253)
Primary was percentage of attempts resulting in erection firm enough for intercourse 1 38%
2 28%
Adverse event withdrawal:
1 5%
2 1.6%
Main adverse events were digestive and nausea
Gontero et al, 2005
Italy
Sublingual apomorphine
Randomised, double-blind comparison of apomorphine 4 mg versus placebo, 4 tablets, in diabetic men R=1
DB=2
WD=1
Total=4
Diabetic men with Ed for 3 months, without previous ED treatment. Mean age 56 years, mean HbA1c 7.9% 1 Fixed dose, 3 mg (n=65)
2 Placebo (n=65)
Improvement in IIEF Improved erections
1 25%
2 21%
Responders (5 point increase in IIEF EF domain
1 23%
2 17%
Nausea
Comparison with sildenafil
Eardley et al, 2004
UK
Sublingual apomorphine
Randomised, crossover, open comparison of sublingual apomorphine with oral sildenafil with dose optimisation R=1
DB=0
WD=1
Total=2
Men with ED, mean age 56 years, mostly white 1 Apomorphine 2-3 mg (n=139)
2 Sildenafil 25-100 mg (n=139)
EF domains of the IIEF Percentage of successful attempts at intercourse
1 35%
2 75%
More nausea with apomorphine, more flushing, headache, dyspepsia, abnormal vision with sildenafil
Perimenis et al, 2004
UK
Sublingual apomorphine
Randomised, open, crossover comparison of 2 mg apomorphine and 50 mg oral sildenafil R=1
DB=0
WD=1
Total=2
Men with ED, mean age 56 years, 85% with comorbidities 1 Apomorphine 2 mg (n=20)
2 Sildenafil 50 mg (n=20)
Percentage of successful attempts Percentage of successful attempts at intercourse
1 63%
2 73%
No information

 

Figure 1: Sublingual apomorphine compared with placebo

Two studies also compared sublingual apomorphine with oral sildenafil in open studies. In the larger of these, using titrated dosing to effect, sublingual apomorphine was much less effective than sildenafil.

In all these studies, nausea was the commonest adverse event with apomorphine.

Comment

While apomorphine is effective, in that it is better than placebo, it is clearly less effective than oral PDE-5 inhibitors.

References

  1. E Dula et al. Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. Urology 2000 56: 130-135.
  2. E Dula et al. Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4 mg apomorphine SL in male erectile dysfunction. European Urology 2001 39: 558-563.
  3. AT von Keitz et al. A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction. BJU International 2002 89: 409-415.
  4. P Gontero et al. Clinical efficacy of apomorphine SL in erectile dysfunction of diabetic men. International Journal of Impotence of Research 2005 17: 80-85.
  5. I Eardley et al. An open-level, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction. BJU International 2004 93: 1271-1275.
  6. P Perimenis et al. Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study. Andrologica 2004 36: 106-110.