Yohimbine

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Yohimbine is derived from the bark of the West African yohimbe tree. It is an indole alkaloid that has been reputed to have aphrodisiac properties for over 70 years. Pharmacologically it is an alpha-2-adrenergic antagonist, and its activity is mediated by blocking these receptors in the brain.

In one study, yohimbine was shown to improve sexual function in men with psy-chogenic ED but had little effect in men with organic ED [56].

Men with psychogenic ED showed a 46% response to yohimbine compared with a placebo response of only 16%. However, only 50% of the men actually achieved an erection sufficient for penetration [56].

However, another study assessed the clinical response at baseline and after two different doses of yohimbine in 18 non-smoking men with organic erectile dysfunction [57]. Of the 18 men, 9 (50%) were successful in completing intercourse in more than 75% of attempts, although the authors note that the yohimbine responders were men with less severe ED [57]. They claimed that yohimbine is an effective therapy for organic ED, contradicting earlier studies.

Ernst and Pittler reviewed and meta-analysed all randomized, placebo-controlled trials of yohimbine monotherapy for erectile dysfunction to determine its therapeutic efficacy [58]. They identified seven trials that demonstrated that yohimbine is superior to placebo (odds ratio 3.85, 95% confidence interval 6.67 to 2.22) and suggested that yohimbine could be considered a reasonable therapeutic option for ED and should be considered as an initial pharmacological intervention [58].

Another meta-analysis of four independent trials from (i) controlled clinical trials of yohimbine (when used alone), (ii) uncontrolled trials examining yohimbine (alone), (iii) controlled trials of yohimbine when used in combination with other drugs and (iv) uncontrolled trials of yohimbine plus other drugs reported a consistent tendency for yohimbine, and for other medications containing yohimbine, to enhance erectile functioning relative to placebo [59].

Lebret and colleagues reported a double-blind, placebo-controlled, three-way crossover, randomized clinical trial to compare the efficacy and safety of the combination of 6 g of L-arginine glutamate and 6 mg of yohimbine hydrochloride with that of 6 mg of yohimbine hydrochloride alone and that of placebo alone [60]. They included 45 patients in their study and demonstrated the on-demand oral administration of the 6 g L-arginine glutamate and 6 mg yohimbine combination is effective in improving erectile function in patients with mild to moderate ED [60].

Whilst many studies have shown improvement in sexual function after taking yohimbine, there are at least an equal number of publications claiming that it has no effect.

Kunelius et al. conducted a randomized, double-blind, placebo-controlled, crossover comparison of a placebo with high-dose yohimbine hydrochloride (36 mg a day orally) in 29 men with mixed-type ED [61]. They found no benefit to yohimbine over placebo as a first-line treatment for mixed-type impotence [61].

Similarly, Mann and colleagues conducted a double-blind, placebo-controlled study in 31 men with ED [62]. They found a therapeutic effect of yohimbine in men with non-organic ED, with a significantly greater improvement in the yohimbine group compared to the placebo group. However, they could not demonstrate any superiority of yohimbine over placebo in the organic group [62].

The usual dose of yohimbine is 15 to 30 mg a day in divided doses. However, larger doses (20 to 30 mg) can be used 'on demand'. A tincture of yohimbine bark has been used as 5 to 10 drops three times a day. There are many side effects even in small doses, and its use is not really recommended. It is also contraindicated in men with cardiovascular and neurological diseases.

Despite encouraging scientific evidence for its effectiveness in ED, yohimbine lacks medical and public acceptance. There are many reasons for this: firstly, dose -response studies are lacking; secondly, other forms of administration, such as sublingual, have not been explored; and continuous versus 'on-demand' yohimbine has not been studied. One expert has suggested that this may be because yohimbine is an old drug that has no patent protection or commercial viability [63].

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