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What is post-SSRI sexual dysfunction (PSSD) and how to know that you have it

Updated: Mar 31, 2021

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.

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.

You might be suffering from PSSD if you had been taking an antidepressant and suffer from newfound symptoms lasting 6-12 months without any sign of improvement. Although not by any means conclusive, I've come up with a classification for PSSD in order to aid me in helping others. Subtypes: 1- Pure PSSD: Pure sexual dysfunction without other symptoms. Symptoms include ED, premature ejaculation or delayed orgasm, genital numbness, etc. These are manifestations of nitric oxide pathway dysfunction, TRPC and TRPV channel dysfunction, sex hormone dysregulation and sex hormone receptor insensitivity, with a possible thyroid involvement. 2- Cognitive PSSD: Sexual symptoms + cognitive dysfunction, but without anhedonia or blunted affect. In this subtype, there's a clear cortical dysfunction (cholinergic and/or glutamatergic, and DA/NErgic) leading to brain fog, reduced intelligence, poor memory, and poor concentration. 3- Excitatory-inhibitory PSSD: Sexual symptoms + cognitive symptoms + either intense anxiety/obsessions or complete loss of the anxiety response. Either severe insomnia or excessive daytime sleepiness. Symptoms do not include anhedonia and blunted affect, or any mesolimbic-cortical pathway dysfunction. This subtype is due to GABA-glutamate dysregulation. Low glutamate PLUS either low GABA (insomnia, anxiety, OCD, panic, paranoia etc) or high GABA (excessive drowsiness, complete loss of anxiety). This type is related to dysfunction of neurosteroids and allopregnanolone, as well as changes of expression of 3α-HSD and 3b-HSD enzymes and blunting of the HPA axis (GR upregulation). 4- Mesolimbic PSSD: Sexual symptoms + GABA-glutamate dysfunction + mesolimbic pathway dysfunction but [u]without[/u] cognitive dysfunction. This subtype most likely involves presynaptic 5HT1A supersensitivity or postsynaptic 5HT1A receptors desensitization, or both, plus phasic (not tonic only) dopamine release dysfunction, and reduced oxytocin and beta endorphin release. 5- Complex PSSD: Sexual symptoms + cognitive symptoms + GABA-glutamate dysfunction + mesolimbic-cortical pathway dysfunction. All previous symptoms PLUS severe anhedonia and blunted/flattened affect. There's a clear central dysfunction involving multiple brain areas, with autonomic nervous system dysfunction on top. This severe subtype most likely involves presynaptic 5HT1A supersensitivity or postsynaptic 5HT1A receptors desensitization, or both. Along with all the previous dysfunctions. There's a cholinergic, dopaminergic, DA/NErgic, GABAeric, glutamatergic, and serotonergic involvement + sex hormone and NO pathway dysfunction on top.


#PSSD is an under-recognized condition in the medical community, with very little research done on the subject. As such, your psychiatrist will most likely brush it off unless they are one of the few souls that recognize it. If you suffer from PSSD, know that you are not alone. There's an entire community with fellow sufferers you can communicate and exchange information with.


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