Did you know that Premature Ejaculation (PE) is the most common male sexual dysfunction worldwide? Millions of men around the world suffer from this debilitating drawback and yet even today it remains one of the most poorly understood phenomena in the medical world. Experts in PE from the International Society of Sexual Medicine (ISSM) define the condition as consisting of three major components: a short time to ejaculation (prior to or within about one minute), lack of ejaculatory control and negative personal impact or distress related to ejaculation. It is known that the pathway resulting in ejaculation is comprised of foci within the brain and spinal cord, yet the exact mechanism of action remains unknown. This has boggled the minds of clinicians worldwide until recently whereby clinical trials with medications called SSRI’s have provided evidence that a pathway called the serotonergic pathway is involved in the ejaculatory mechanism.
Now SSRI stands for selective serotonin reuptake inhibitor and in plain English what this means is that they work on receptors in your brain to keep the “happy particle” (serotonin) from being eliminated too quickly. As a result these medications have been proven to be very safe and effective antidepressants in recent years with the beneficial adjunct of lengthening ones time in the bedroom. Despite numerous studies the complete mechanism of action of SSRI’s in relation to PE is not fully understood, although what is known is that the type of SSRI used is important in the efficacy of the treatment. It has been shown that one of the SSRI family medications dopoxetine (priligy) is claimed to be particularly effective, compared to other SSRIs, when given acutely even as suddenly as after the first dose. This is exciting news as other SSRI’s used in the past are known to take a very long time to provide the patient with any clinical benefit.
The interesting thing about dopoxetine is that after large clinical trials for use as an antidepressant it failed because it doesn’t hang around in the body for as long i.e. it has the shortest half-life of all SSRI medications. However this has been shown to be favourable when it comes to the treatment of PE as it provides faster clinical benefits with fewer side effects than comparable SSRI’s. For example other SSRI’s take on average 3-4 weeks to show clinical benefit whereas clinical trials with dopoxetine showed that clinical benefit is achievable in 1 week.
Although it has been mentioned that the exact mechanism of SSRI action in PE is unknown, we can reasonably assume that in depression, clinical efficacy is generated by an adaptive change in the brain that stops serotonin from being eliminated as quickly as it would do in a patient not on SSRI treatment. If this is true it is easy to explain why all SSRI’s are not clinically equivalent and that is because they are not all used at the equivalent dosage to inhibit serotonin elimination to the same degree. Although this may be true for depression, studies have shown that simply raised levels of serotonin in the brain and not an adaptive change may bring about clinical benefits in PE. In other words if you take a medication that straight away raises the level of serotonin in your brain you will get clinical benefit in treating PE but not depression. This is because with depression you must wait for an adaptive change in the brain to occur whereas in PE it is simply enough to acutely raise the levels of serotonin.
As mentioned earlier dopoxetine has the shortest half-life and thus will have the quickest clinical effect because appropriate levels of serotonin will be reached within a short period of time. This is unlike the other SSRI medication that can take weeks to reach the effective level of medication in the body. The reason then that this is good for PE and not depression is simply due to the fact that a steady level of SSRI over a long time is best in managing depressive symptoms due to the required adaptive change in the brain. However in PE taking the medication (dopoxetine) prior to sexual intercourse and in turn raising that level of serotonin for that period of time and not at all times is best. So because of the ability of dopoxetine to raise the level of serotonin in ones brain acutely and not chronically it makes for a good PE treatment. This is also reassuring to the patient because taking dopoxetine “on demand” (1-3 hours prior to sex) will not alter the function of the serotonergic pathway in the same way as other SSRI’s as an adaptive change is not required by the brain in order to have an effective mechanism of clinical action.
Although clarity is required on the exact mechanism of action of these medications it can be said that the discovery of the beneficial effects of dopoxetine on PE is an exciting medical breakthrough. This medication known by the trade name of priligy as of the 10th of February 2010 was released for prescription only use in Sweden and Finland and is the first tablet form of medication of its kind. It has been extensively evaluated in five randomised, placebo-controlled Phase III clinical trials involving more than 6,000 men with PE and their partners. As a result this is the most comprehensive not to mention the largest clinical trial to date re the use of drug therapy to treat PE. All going well it will hopefully be available in the US in the not too distant future.