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July 10, 2020
Post-SSRI-Sexual-Dysfunction (PSSD) is a fairly new, unexplored and underdiagnosed iatrogenic condition, that arises for individuals following the use of antidepressant medication. R
The symptoms of PSSD can start days or weeks after beginning SSRIs and can persist after discontinuing SSRIs. R
In fact, PSSD also can present after a single dose of an antidepressant. R
SSRIs can cause long‐term effects on all aspects of the sexual response cycle that may persist after they are discontinued. R
Different theories have been proposed to explain the pathophysiology of PSSD: R
Sexual behavior is impaired by many 5-HT agonists and agents that increase 5-HT. R
Serotonin (5-HT) is primarily inhibitory, although stimulation of 5- HT2C receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT1A receptors has the opposite effects like facilitation of ejaculation and, in some circumstances, inhibition of erection. R
Stimulation of other 5-HT2 receptors hypothetically mediates several of the side effects of the SSRIs sexual dysfunction. R
Excessive release of serotonin (which has a mixed but essentially inhibitory role on sexual functions) by the serotonergic neurons (concentrated in the raphe nuclei of the midbrain) causes "desensitization" of 5-HT1A autoreceptors (that act as sentinels that regulate the release of a substance according on how much there is already in circulation). R
The "down-regulation" of the 5-HT1A autoreceptors is instead caused by chronic and excessive activation by its natural "agonist" (serotonin) that is made available in abnormal quantities by the use of SSRIs. R
It is therefore natural to think to the autoreceptors as something that is "damaged" by excessive competition and that can be cured using an antagonist that lead the person to be again "sensitive." R
For example, when rodents were administered an SSRI medication, they noted a sustained desensitisation of 5-HT1A receptors after removal of the drug. R
In another study, a 5-HT1A antagonist was shown to reverse and prevent sexual dysfunction in rodents that were being administered with fluoxetine. R
However, PSSD sufferers through online support forums have tried and reported on the effects of all combinations of medicines acting on serotonin and dopamine systems, and medicines known to enhance functionality (ie sildenafil), are without benefit. R
It is also hypothesized that SSRI treatment induces disturbances of Transient Receptor Potential (TRP) ion channels of mechano-, thermo- and chemosensitive nerve endings and receptors resulting in the penile anesthesia in PSSD. R
