PSSD Cures? How To Reverse Post-SSRI-Sexual Dysfunction.

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Lucas Aoun

Founder @ BYB

July 10, 2020

Post-SSRI sexual dysfunction (PSSD) is a protracted syndrome that begins after quitting antidepressants and remains for months or even years on end. Symptoms are numerous and can be life-disabling.

Key Facts

Antidepressants can trigger PSSD from just a few pills in the unlucky few, depending on genetic vulnerability. Symptoms can be fully present or partially present, depending on which pathways are affected:

  • Erectile dysfunction.
  • Premature ejaculation or delayed orgasm.
  • Genital numbness.
  • Cognitive dysfunction (brain fog, poor memory, etc)
  • Anhedonia (inability to feel pleasure)
  • Apathy
  • Blunted affect (Flattened emotions)
  • Insomnia or excessive daytime sleepiness.
  • Intense anxiety or complete loss of the ability to feel anxiety.
  • OCD, panic, paranoia.
    (Meso, 2021).

What Is Happening In The Brain?

Different theories have been proposed to explain the pathophysiology of PSSD: R

  • Cytochrome actions
  • Dopamine-serotonin dysfunction.
  • Desensitized/downregulated 5HT1-A Receptors.
  • Epigenetic gene expression
  • Hormonal changes in the central and peripheral nervous systems
  • Proopiomelanocortin (POMC) and Melanocortin effects
  • Serotonin neurotoxicity

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

The raphe-to-spinal projections are serotonergic with receptors subtypes 5HT1A, 5HT1B, 5HT2A and 5HT2C (formerly known as 5HT1C) present [11].

5HT1A receptor: Anti-erectile, both pre-synaptically and post-synaptically [12] [13] [14] [15].

5HT1B receptor: Anti-erectile similarly to 5HT1A receptors [12] [16].

5HT2A receptor: Data on its effect on erection is insufficient [17] [21].

5HT2C receptor: Pro-erectile. Directly opposes the anti-erectile effect of 5HT1A receptor, but might be following an inverted U-shaped curve [18] [19][22][23]. Chronic activation might by anti-sexual though inhibition of melanocortin MC4 receptors by 5HT2C and 5HT2A agonism [20].

Supplements That Have Helped Some PSSD Cases:

  • Phosphorus (30C homoeopathic remedy)
  • EDOVIS (L-Citruline, Tribulus Terrestris, Maca, Damiana, Muira Puama, and Folic Acid) R
  • Ginkgo Biloba R
  • Maca R
  • Saffron R
  • St John’s Wort (via upregulating 5-HT1A receptor) R
  • Yohimbine R
  • Zeolite R

More can be found here:

What To Avoid:

  • Antidepressant medications that possess SSRI, SNRI properties R
  • Ashwagandha -
  • Berberine can worsen symptoms via acting on the 5-HT1A receptor R
  • Ginseng may worsen symptoms for PSSD users, since it may act as a mild SNRI R
  • Herbal 5-HT1a partial agonists such as Ginger R


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