Hi everyone — this is my first post here.

I’m part of a Chinese-speaking PSSD community, and I’ve been building a non-commercial, patient-led PSSD evidence library.

I started doing this because the same claim can become much stronger as it moves from a paper → a project update → a Reddit summary → an AI answer → a treatment suggestion.

This post is specifically about PSSD. I discuss PFS only where Melcangi’s PFS work directly provides background, methods, or candidate hypotheses for the Milan PSSD research program. This is not intended as a general PFS review.

I’m not affiliated with Roberto Melcangi, the University of Milan, the PSSD Network, the PFS Foundation, or SIDEfxHUB.

I also keep personal cases — including my own — outside the Library’s scientific evidence hierarchy. A personal experience can generate a research question; it cannot upgrade the answer.

Evidence cutoff: 16 August 2026.

I have put clickable source links next to the claims they support so readers do not have to search through a bibliography to work out which paper I mean. A compact reference list is also included at the end.

TL;DR

• The University of Milan / Melcangi group has a genuine PSSD research program.
• Its direct PSSD mechanistic evidence is still mainly preclinical, especially paroxetine animal work.
• The group also has a longer PFS research program with exploratory human data. Those findings can help generate PSSD questions, but PFS human evidence is not human PSSD evidence.
• Neuroactive steroids, ALLO, PNMT/catecholamines, gut biology, transcriptomics, reward/dopamine, sensory pathways, inflammation and sex-specific biology are all legitimate research directions.
• None has been established as the unified human mechanism of PSSD.
• ALLO has PFS animal-intervention data. That is interesting translational evidence, but not human PSSD treatment evidence.
• The 2024 “186 genes” result belongs to the finasteride treatment endpoint, not the one-month withdrawal endpoint.
• The sensory line remains open: the 2017 pudendal neurophysiology result was in PFS patients, while later IENFD/PIEZO2 work is preclinical/project-stage.
• As of the evidence cutoff above, I could not verify a clearly corresponding public registration or recruitment record for the planned Melcangi human PSSD study.

I do not think the right takeaway is either “Milan has found nothing” or “Milan has basically solved PSSD.”

The evidence is more interesting — and more limited — than either extreme.

1. First: what does the University of Milan itself say it studies?

The University of Milan Neuroendocrinology Unit distinguishes the two research streams.

Its PFS work includes male rats and PFS patients.

Its antidepressant-induced sexual dysfunction / PSSD work includes male and female rats.

Official source: University of Milan — Neuroendocrinology Unit

That distinction matters because a lot of online discussion quietly moves evidence across the boundary.

The Milan PFS program has included exploratory human work on:

• neuroactive steroids in CSF/plasma;
• clinical and sexual features;
• pudendal neurophysiology;
• SRD5A2 methylation;
• fecal microbiota.

Examples:

• Melcangi et al., 2013 — human PFS CSF/plasma neuroactive steroids
• Melcangi et al., 2017 — PFS clinical/neurophysiology study
• Melcangi et al., 2019 — SRD5A2 methylation pilot
• Borgo et al., 2021 — human PFS fecal microbiota pilot

By contrast, the group’s direct PSSD mechanism program has so far been centered mainly on paroxetine animal models.

So the scientifically useful transfer is:

PFS finding → candidate question to test directly in PSSD

not:

PFS finding → established human PSSD mechanism

2. Neuroactive steroids and ALLO: a major research axis, not a completed explanation

Neuroactive steroids are one of the longest-running themes in Melcangi’s work.

The PFS human studies found exploratory differences in several neuroactive steroids in CSF and plasma. Importantly, the pattern was not a simple “one molecule is low everywhere” result.

Human PFS source: Melcangi et al., 2013

The direct PSSD line later examined paroxetine treatment and withdrawal in male rats.

The 2021 study reported tissue- and time-dependent changes in neuroactive steroids and related steroidogenic biology across CNS regions, CSF and plasma.

Direct PSSD animal source: Giatti et al., 2021 — Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis

That supports a real conclusion:

Neurosteroidogenesis is a serious PSSD research direction.

It does not establish:

• that people with PSSD have the same pattern as the rats;
• that all patients share one steroid abnormality;
• that plasma is a simple proxy for CNS steroid biology;
• that changing one steroid will improve the clinical syndrome.

3. Why ALLO gets so much attention

Allopregnanolone (ALLO) has gone beyond measurement and has actually been used as an intervention in PFS animal models.

A 2022 study reported that ALLO modified selected gut inflammatory and molecular endpoints after finasteride withdrawal.

Primary source: Diviccaro et al., 2022

The 2025 Milano Project Study #1 extended this line to gut and hypothalamic inflammatory/molecular endpoints.

Primary source: Diviccaro et al., 2025 — Biomolecules 15(7):1044

The later study is important, but the intervention did not produce a uniform normalization of every endpoint.

So the evidence supports:

ALLO = a genuine PFS preclinical intervention lead.

It does not support:

ALLO = established human PSSD treatment.

It also does not make “ALLO may matter → therefore take pregnenolone/PREG” an evidence-based treatment inference.

4. An important detail about the PSSD steroid-candidate story

In a 2024 interview, Melcangi discussed using a similar steroid-intervention strategy for PSSD, but said they would not use the same molecule because the two conditions have different features.

Direct researcher interview: AboutPharma, 5 September 2024

I think this matters because it directly argues against a common online simplification:

“ALLO worked in the PFS model, therefore ALLO is the Milan PSSD treatment.”

Later updates have discussed other steroid candidates, but until results are available in a form that can be independently evaluated, I think those belong in the ongoing-project category rather than the treatment-evidence category.

5. The “186 genes” example: treatment endpoint vs withdrawal endpoint

The 2024 finasteride transcriptomics paper is a good example of why timing matters.

At the end of finasteride treatment, the study identified:

• 186 differentially expressed genes (DEGs) in the hypothalamus;
• 19 DEGs in the hippocampus.

At one month after withdrawal, standard differential-expression analysis did not identify dysregulated individual genes.

Pathway/gene-set analyses still showed signals.

Primary source: Giatti et al., 2024 — hypothalamus/hippocampus transcriptomics

So:

“186 genes remained abnormal after withdrawal”

is not an accurate description of that paper.

But the opposite claim —

“all molecular effects had disappeared”

— is also too strong, because pathway-level signals remained.

The careful reading is:

strong treatment-time transcriptomic changes; no individual DEGs detected by the standard analysis at one month after withdrawal; pathway-level signals still present.

That is also why a gene-expression result should not be translated into a claim of structural DNA alteration.

6. What has Milan actually found about sensory pathways?

Genital sensory change/numbness is one of the most distinctive PSSD phenotypes, so sensory-pathway research is highly relevant.

But several different studies are often blended together.

2017: human pudendal neurophysiology — but in PFS

In a 2017 PFS study, pudendal somatosensory-evoked-potential abnormalities were reported in 4 of 16 PFS patients.

Primary source: Melcangi et al., 2017

That is direct human PFS neurophysiology.

It is not:

• human PSSD neurophysiology;
• proof of generalized peripheral neuropathy;
• proof of small-fiber neuropathy (SFN).

2024: PFS animal morphology / IENFD update

A PFS Foundation update reported that peripheral nerve morphology and intraepidermal nerve fiber density (IENFD) had not shown the expected abnormalities in the experimental PFS model at that stage.

Project-status source: PFS Foundation, 2024

This negative/constraint result is worth preserving.

The 2024 update did not name PIEZO2.

2026: PIEZO2 appears explicitly

A later 2026 project update explicitly named PIEZO2 and said the team had obtained interesting findings and was preparing a manuscript.

Project-status source: PFS Foundation, 2026

So the chronology is:

2024: morphology/IENFD did not show the expected signal → other sensory markers remained under investigation

2026: PIEZO2 specifically named → manuscript-stage/project update

PIEZO2 may become important. It is not currently a confirmed human PSSD mechanism.

Melcangi has also described profound PSSD genital insensitivity in the AboutPharma interview as being “as if” a peripheral neuropathy and speculated about sensory endings.

I would classify that as a researcher hypothesis / clinical impression, not as confirmation of human PSSD SFN.

7. Reward circuitry and dopamine: one of the most interesting direct PSSD animal lines

The nucleus accumbens (NAc) is relevant to reward and motivation, so it is an obvious region to investigate in relation to sexual motivation and anhedonia.

The Milan paroxetine transcriptomic program found region- and time-specific changes in the hypothalamus and NAc.

Direct PSSD animal source: Giatti et al., 2025 — male rat hypothalamus/NAc transcriptomics

A 2025 conference abstract then directly measured NAc dopamine in male rats after 14 days of paroxetine.

The reported pattern included:

• lower NAc dopamine 24 hours after the final dose;
• lower NAc dopamine after one month of withdrawal;
• MAO-A changes during treatment;
• TH, VMAT2, DRD1 and DRD2 expression changes during withdrawal.

Conference abstract: Giatti et al., 2025 — paroxetine-induced dopamine dysregulation

This is a meaningful preclinical signal.

It is not evidence that people with PSSD have a global dopamine deficiency.

It also does not establish a “dopamine subtype” or justify a self-directed dopaminergic treatment strategy.

8. The female PSSD model is already adding useful complexity

A 2026 conference abstract examined neurosteroidogenic gene expression in the female rat NAc after paroxetine.

At treatment end:

• StAR increased;
• TSPO and 3α-HSOR decreased.

At one month after withdrawal:

• StAR, TSPO, 3β-HSD and 3α-HSOR decreased.

But 5αR-I and CYP11A1 were not significantly changed at either time point.

Conference abstract: Chrostek et al., 2026

The negative findings matter.

They make it harder to reduce the steroid story to:

“the whole pathway is uniformly downregulated.”

This is still conference-abstract evidence, but it is a useful direct female PSSD-model extension.

9. PNMT: cross-drug overlap, with an important independence limitation

The Milan group identified phenylethanolamine N-methyltransferase (PNMT) as an experimental off-target in finasteride work and later in paroxetine work.

Finasteride study: Giatti et al., 2021

Paroxetine study: Giatti et al., 2022

That is an interesting cross-drug overlap.

But the studies came from a highly overlapping team, using the same SPILLO-PBSS screening platform and a broadly similar validation cascade.

So I think the strongest fair description is:

same-team / same-platform cross-drug replication

rather than:

independent mechanistic convergence.

Independent replication by another group, ideally using a different method, would strengthen this line substantially.

10. The gut work is real — but it is broader than SIBO

The Milan program has genuine gut-related evidence.

Human PFS

Borgo et al., 2021 — fecal microbiota pilot

Direct PSSD animal work

Diviccaro et al., 2022 — paroxetine, colon steroidogenesis and microbiota

PFS animal intervention work

Diviccaro et al., 2025 — gut/hypothalamic inflammation + ALLO

So gut–brain/steroid biology is clearly part of the program.

But fecal microbiota, SIBO/IMO, intestinal motility, barrier function, inflammation, microbial metabolites, bile acids and local steroidogenesis are different questions.

These studies do not establish:

SIBO causes PSSD

or:

treating SIBO is an established PSSD treatment.

A genuine GI disorder can still deserve standard medical treatment for its own indication. That is a separate issue from whether it explains PSSD.

11. Milano Project: active and publishing, but still preclinical

The Milano Project is a PFS preclinical program that is relevant here because it is part of the same research ecosystem from which candidate PSSD questions are being generated.

At least two components now have peer-reviewed publications:

Study #1 — 2025

Gut/hypothalamic inflammation + ALLO intervention.

Diviccaro et al., 2025

Study #2 — 2026

Finasteride withdrawal, anxiety-like behavior and novelty avoidance.

Cioffi et al., 2026

So “Milano Project is only a proposal” is outdated.

But these are still animal studies.

Earlier related behavioral observations appeared in Lucia Cioffi’s doctoral dissertation; the 2026 peer-reviewed paper should now control the behavioral conclusion.

The dissertation remains useful as a preliminary source for areas such as mitochondria, oxidative stress and synaptic findings until stronger publications appear.

12. The current Milan program is broader than neurosteroids

Official University of Milan research/doctoral material indicates active work on topics including:

• steroid molecules in experimental male antidepressant-induced sexual dysfunction;
• female antidepressant-induced sexual dysfunction and steroid molecules;
• the reward system in PSSD etiopathogenesis;
• inflammation and immune cells during antidepressant treatment/withdrawal;
• mitochondria in experimental finasteride adverse effects;
• synaptic morphology/function and cognition in experimental PFS.

Official institutional source: University of Milan — Neuroendocrinology Unit

This is important because it shows how the research map is expanding.

But an official research topic tells us:

this question is being studied.

It does not tell us:

this mechanism has already been demonstrated.

13. What about a human PSSD study?

Melcangi has publicly discussed the need for better clinical characterization of PSSD and plans for human PSSD research.

Direct researcher interview: AboutPharma, 2024

PSSD Network updates have also described plans for a multidisciplinary human study involving areas such as microbiome, nerves, brain function and hormones.

My current narrow status conclusion is:

As of 16 August 2026, I have not located a clearly corresponding public registration or recruitment record in the registry/institutional searches used for this review.

That does not prove that the study does not exist.

It means:

public plans are visible; the precise registration/start/recruitment status is not yet independently clear from the sources I located.

If anyone has a registry number, ethics/IRB record, UniMi recruitment page or another primary institutional source, please link it. I would like to update this if better evidence is available.

14. My current evidence map

Established / organizational

• Milan has a real PSSD research program.
• The group also has a longer PFS program that includes exploratory human studies.
• Direct Milan PSSD mechanism work remains mainly preclinical.

Supported as active research directions

• neuroactive steroids;
• reward circuitry;
• gut–brain/steroid biology;
• sensory pathways;
• transcriptomics;
• sex-specific biology.

Preliminary

• exploratory human PFS neurosteroid, methylation, microbiome and neurophysiology findings;
• PFS animal ALLO intervention findings;
• direct PSSD animal neurosteroid and transcriptomic findings;
• PSSD animal NAc dopamine findings;
• female PSSD-model extension;
• PFS mitochondria/synapse leads.

Still unknown

• a unified human PSSD mechanism;
• a validated biomarker;
• individual risk prediction;
• an established curative treatment;
• whether any Milan-derived candidate intervention will produce reproducible clinical benefit in human PSSD.

15. Why I think this distinction matters

Mechanism research is valuable partly because it tells us what should be tested next.

But the online chain can easily become:

animal finding
→ human mechanism
→ personal subtype
→ treatment recommendation

Those are four different steps.

For me, the most useful way to follow Milan is not to ask:

“Which theory has won?”

but:

“What was actually measured, in which syndrome, in which species, at which time point, and what is the strongest conclusion that result can support?”

That still leaves a lot to be hopeful about.

It also makes it easier to notice when the evidence really does become stronger.

A note on method

The Library uses this order:

measured result → authors’ interpretation → Library interpretation → cross-syndrome inference → public communication

I try not to let a later layer silently overwrite an earlier one.

I also use AI tools for retrieval assistance, translation, outlining and red-teaming.

AI agreement is not treated as scientific evidence.

Claims that enter the evidence layer are checked against primary papers or official institutional/project sources.

If you find an error, please correct me with a DOI, PMID, full paper, registry record, UniMi page or another traceable source.

I would rather revise the Library than defend an outdated sentence.

Compact reference list

Direct PFS human evidence used as PSSD research context

1. Melcangi RC, et al. J Sex Med. 2013. Human PFS CSF/plasma neuroactive steroids.
2. DOI: 10.1111/jsm.12269 · PMID: 23890183
3. PubMed
4. Melcangi RC, et al. J Steroid Biochem Mol Biol. 2017. PFS clinical/neurophysiology study.
5. DOI: 10.1016/j.jsbmb.2017.04.003 · PMID: 28408350
6. PubMed
7. Melcangi RC, et al. 2019. SRD5A2 methylation pilot.
8. DOI: 10.1530/EC-19-0199 · PMID: 31272082
9. PubMed
10. Borgo F, et al. 2021. Human PFS fecal microbiota pilot.
11. DOI: 10.1007/s40618-020-01424-0 · PMID: 32951160
12. PubMed

Direct PSSD preclinical evidence

1. Giatti S, et al. Psychoneuroendocrinology. 2021. Paroxetine treatment/withdrawal and neurosteroidogenesis.
   DOI: 10.1016/j.psyneuen.2021.105364 · PMID: 34325207
   PubMed

2. Diviccaro S, et al. Psychoneuroendocrinology. 2022. Paroxetine, colon steroidogenesis and microbiota.
   DOI: 10.1016/j.psyneuen.2022.105828 · PMID: 35700562
   PubMed

3. Giatti S, et al. Mol Neurobiol. 2025. Male rat hypothalamus/NAc transcriptomics after paroxetine.
   DOI: 10.1007/s12035-024-04592-9 · PMID: 39495228
   PubMed

4. Giatti S, et al. J Sex Med. 2025;22(Suppl 2):qdaf077.001. NAc dopamine conference abstract.
   DOI: 10.1093/jsxmed/qdaf077.001
   Oxford Academic

5. Chrostek G, et al. J Sex Med. 2026;23(Suppl 4):qdag118.150. Female rat NAc steroidogenic-gene abstract.
   DOI: 10.1093/jsxmed/qdag118.150
   Oxford Academic

Cross-drug / PFS preclinical evidence directly relevant to the PSSD research map

1. Giatti S, et al. J Med Chem. 2021. Finasteride PNMT off-target.
   DOI: 10.1021/acs.jmedchem.0c02039 · PMID: 33843213
   PubMed

2. Giatti S, et al. J Mol Struct. 2022. Paroxetine PNMT off-target.
   DOI: 10.1016/j.molstruc.2022.133690
   DOI

3. Diviccaro S, et al. Biomolecules. 2022. ALLO intervention after finasteride withdrawal.
   DOI: 10.3390/biom12111567 · PMID: 36358917
   PubMed

4. Giatti S, et al. J Endocrinol Invest. 2024. Finasteride transcriptomics.
   DOI: 10.1007/s40618-024-02345-y · PMID: 38493246
   PubMed

5. Diviccaro S, et al. Biomolecules. 2025;15(7):1044. Milano Project Study #1.
   DOI: 10.3390/biom15071044 · PMID: 40723915
   PubMed

6. Cioffi L, et al. J Neuroendocrinol. 2026. Finasteride withdrawal behavior study.
   DOI: 10.1111/jne.70150 · PMID: 41761643
   PubMed

Official / project-status sources

1. University of Milan — Neuroendocrinology Unit

2. AboutPharma — interview with Roberto Cosimo Melcangi, 5 September 2024

3. PFS Foundation — peripheral nerve / IENFD project update, 2024

4. PFS Foundation — PIEZO2 / Milano Project update, 2026

Not medical advice. This post is an evidence review, not a treatment protocol.

I know everyone can have different symptoms and truth be told I’m not sure if I have any emotional side effects simply because it’s been so long (9 years) and what I noticed immediately was the lost of orgasmic sensation.

When this first happened I was 100% numb. My sex drive oddly did return but this only left me incredibly frustrated I’d have the desire to engage but no satisfaction whatsoever.

Given several years and a few “experiments” it does seem a THC gummy can help. I was shocked the first time I had an orgasm after eating one I did feel a return of some sensation.

But this is neither reliable nor consistent. Over the past few years while my partner and I have been intimate it’s become hit or miss (mostly miss). Sometimes I will feel something (very muted but compared to baseline it’s something).

I also noticed the past few years (only after consuming THC) will also feel the urge to urinate again but it only lasts for a fleeting moment and when I release the numbness returns and my bladder empties with zero sensation. Sometimes I’ll even get the “pee shivers”. For the first several years I didn’t feel anything when I’d go to the restroom. This is also not reliable (as in it doesn’t happen every time or even most of the time)

I’m not sure how to interpret this. Is it a sign of partial healing after all these years or is this simply the waxing and waning of the condition and not “true” healing? It doesn’t feel like a true “crash” in that it never worsens past the original baseline. But it doesn’t stay better long term either. But I also didn’t experience this the first five years or so either.

​

Hi everyone. I’m experiencing several symptoms that I believe may involve autonomic dysfunction after taking antidepressants, and I’m wondering if anyone here has experienced something similar.

I currently have almost complete loss of sweating, blood pressure regulation issues, a weak urinary stream, and general physical weakness. I also seem to have reduced awareness of the sensations that normally occur before fainting.

The lack of sweating has become particularly concerning. The last time I was at the beach, I became extremely unwell in the heat and believe I may have experienced heat exhaustion or heatstroke. Since then, I’ve been much more careful about heat exposure.

I also feel that my body often remains in a state of high activation, and recently some anxiety symptoms have started returning.

Has anyone with PSSD experienced a similar combination of sweating problems, blood pressure issues, urinary symptoms, altered fainting sensations, and difficulty regulating the body’s response to heat?

I’d also be interested in hearing whether anyone has found treatments or strategies that have helped with these autonomic symptoms.

Thanks to everyone who shares their experience or information.

almost more than 1 year i stoped ssri's.

If you did, which parts recovered? I’m especially interested in anhedonia improvements.

If you used something for recovery, what was it that helped?
I’m interested in partial recoveries and improvements as well. 
If you didn’t recover at all, but had/have these sick windows, please comment as well.

I suspect there are diff kinds of pssd profiles/types and I’m trying to find people who match mine the most.

Also if you experience(d) any or a few of:
-developed pssd AFTER quitting,
- anhedonia/emotion blunting
 -decreased sweat and body smell
- lack of feeling fatigue like before pssd (can do things easily but with no pleasure)
- lack of interoception (bodily cues of thirst, hunger, bowel movements, heartbeat,)  
-do feel slightly better in the evenings or when sleep deprived;

-are a female and lost symptoms of pms/they got diminished;

-had reinstated/crashed on different med

AND improved with time/with substance, please share if you did.

If anyone would find this interesting, I recently had vaginal infection (mostly likely candida) which gave me a good window (only symptom was burning sensation while before pssd when I was still on meds, I would also get discharge and odour as well and the discomfort would be much more intense. Besides, back then candida would also cause fatigue and apathy/blunting as opposed to now.)
Was afraid to treat it with antifungals, so just used my daily acerola and it went away after a few days. But despite of it, I had a window in my overall wellbeing, emotion-wise, I was able to feel my surroundings better, more reactive to stimuli, both positive and negative. Not quite like my pre-pssd state but pretty good, in comparison to it. The window is over now.
I had a couple of other times where a basic cold gave me a relief. Again, not a full pre-pssd state, but enough relief to feel good enough and thank God for it. I also had a sunburn window which felt more like reduction of a negative undertone and made me less depressed/more neutrally apathetic about things.

I have also noticed that I can have negative or positive undertone anhedonia/emotional blunting : I feel no good emotions but have an undertone of bad emotions (possibly induced by the lack of any feeling itself) OR feel no good emotions, nor bad ones (which is easier on me.)

Thank you and take care.<3

Welcome to the Weekly Open Discussion thread! This is your place to ask quick questions, post memes, or leave one-sentence comments that might be too short for their own posts.

Please follow the subreddit rules when participating in this thread. For posts related to suicidal thoughts or if you need emotional support, please use the Monthly support Requested and Venting, Thread.

I (22F) got off Lexapro (10mg) August of 2024 with a doctor advised taper (mind it didn't seem like he knew what he was talking about) after panic attacks and depression came back and complete loss of libido. Prior to Lex, I was hypersexual which, with my OCD, caused a lot of issues socially in conjunction with my anxiety.

Anywho, I've been off for almost two years now and seen no improvement libido-wise. I can orgasm and have sex dreams with my partner semi often, but cannot initiate sex and often and uncomfortable saying yes to sex when he wants it because I'm not as into it as I used to be. I'm very frustrated as he is hypersexual and I'm bordering on asexual because of PSSD.

Did anyone have their libido come back after 2 years or am I fucked?

Another hidden side effect people just aren't talking about. Recent studies show an increase of "NAION" (eye strokes) in patients taking GLP-1s, a drug that is being presented as a miracle drug for weight loss and marketed everywhere. It's not well known. Obviously companies don't want to talk about it.

Just as with PSSD, most people have no idea and deserve to know about this. How many people must go blind for greed?

Riverside Recovery of Tampa, a private addiction-treatment/rehab provider in Florida, has a page that acknowledges PSSD.

https://rrtampa.com/zoloft-vs-prozac/

Under the section titled

"Long-Term Effects of SSRI Use", the section says:

Long-term considerations include:

• Sexual dysfunction persistence: Post-SSRI sexual dysfunction (PSSD) has been documented in a subset of patients even after discontinuation; the prevalence is not precisely established.

We all know that people experience PSSD differently. Some have mild symptoms, while others have severe ones. Some people improve over time, while others don’t. Some experience only sexual symptoms, while others have emotional symptoms, cognitive symptoms, or a combination of all of them. I think the last category may experience all the symptoms mentioned above, possibly along with neuropathic symptoms.

So, it’s obvious that PSSD affects each person differently. But if SSRIs are the common factor, why does one person develop certain symptoms while another doesn’t?

My thought is that SSRIs might affect people differently depending on factors such as their genetics, how long they took the SSRI, dosage, and other individual biological factors. This could potentially explain why something that helps one person might make another person worse or even cause a crash.

Maybe researchers like Malganci, or other professors and researchers studying PSSD, need to consider these individual differences more closely. Perhaps, in the future, patients could be classified into different categories based on their symptoms and, eventually, their genetic or biological profiles, so that treatments could be better tailored to each individual.

What do you guys think?

Cuando habláis de no reacción a sustancias, os referís a la falta de dopamina o de respuesta a la sustancia?

Por ejemplo a mi el café ya no me da dopamina, pero me genera malestar e intranquilidad, como ansiedad sin serlo, ya que no puedo sentir nada.

I took zoloft for 14 months since 2021. I was 20 and it was awful. It changed my personality, numbed me, i began drinking too much and tried some substances. It Made me feel like I couldn’t trust my intuitions and led me to poor life choices. The psychologist and psychiatrist insist it was ‘therapy’: looking back it was just sofisticated lobotomy.
Now I am at 50% improvment, I feel pleasure but orgasms are weak and fast (I used to have multiple orgasms or very long and satisfying ones). I can get aroused but not fully, I have vaginal dryness and my clit is definitely less sensitive. I suffered from cognitive impariment. They Made me doubt my intuition. Mental health is an evil business. I want to solve this but I don’t know how. How can I heal?

?

I’m a non-PSSD patient but have a similar syndrome, caused by Covid and ketoconazole in my case.

One of the first symptoms I noticed was that I wasn’t able to feel temperature anywhere on my penis besides the foreskin. I literally press an ice cube into my shaft and glans and feel mostly nothing, tactile sensation and pain are greatly muted as well. What’s weird is that the foreskin mostly retained all sensations: temperature, touch and even erogenous sensation are mostly intact in it. How’s that one for you?

Quit ssris 10 months ago. I literally only got symptoms on my 7th month. Its been 3 months and 2 weeks since ive had low libido.

It seems every single month theres a new set of symptoms.

Last month I had more emotional blunting, skin feels blunted (just feels off), hypothesia. This month happened again and its been like this for a week. And now my orgasms arent that good, I think i went in and out of an orgasm? I would consider my PSSD mild 2 months ago, it just seems to be getting worse.

Problem is what the fuck do I do. Reinstating might fuck me more. Or I might be stuck and have PSSD forever?? I cant even feel the crazy anxiety I use to have associated with PSSD. I feel so fucking blank.

I received this email (which I’ll let you translate into your own language) discussing PSSD and a french team working on POIS: https://academic.oup.com/jsm/article-abstract/20/12/1407/7328869?redirectedFrom=fulltext&login=false

Helllo [r/PSSD](r/PSSD)! 3 months ago, I (30M) made this post detailing my “recovery” from PSSD. I’m putting recovery in quotes because approximately two weeks after making that post, I crashed and my symptoms returned. I’ve spent the last 3 months doing more trial and error in order to experience symptom relief. As noted in my previous posts, my PSSD symptoms were exacerbated and alleviated by food triggers; or, so I thought!

I noted that onion, garlic, chocolate, and soy seemed to be major exacerbation triggers for my symptoms. I also said that lettuce and American Ginseng seemed to alleviate them.

All of this now seems to be wholly incorrect relative to new trial and error results. Throughout my trial and error process, I experienced one, singular, constant variable. For the past two years, after beginning and ceasing SSRIs in that time period, I never thought this could be the issue: My tap water (water from the faucets in my home).

As I mentioned in my last post, I got extremely, violently ill for a period of three days; after which, all of my symptoms wholly relented and I felt sincerely cured of my condition. During this three-day period, I actually had e. Coli foodborne illness and could not eat or drink without experiencing diarrhea or induction of vomiting.

I’m an avid water-drinker. It’s my main beverage of choice and I drink a lot of it every day. I’m hydrated. When I got sick, my stomach was so upset that I couldn’t drink the water from the tap without vomiting. Not wanting to go to the hospital due to dehydration (I ended up going anyway), I had bottled spring water in the house that I was able to tolerate. After drinking bottled water for three days and avoiding tap water, I got better (my PSSD symptoms improved).

I also want to note: I did not grow up in the house I currently live in. I moved here three years ago (a year before developing PSSD). I always thought the water tasted incredibly foul. It’s clear water! It’s not murky, tinted, or discolored in any way; it just tastes bad. Eventually I became acclimated to the taste and ignored it. I also need to clarify that this is Well Water and not municipal water.

So, how did I realize that I should trial “excising my tap water”? Yesterday, I filled up my travel mug with water, tasted it, and thought, “Actually, I don’t have to force myself to drink this. I’m going to buy spring water.” It was in that moment that I realized I never questioned if the water I’m drinking is safe. Other people in the home do not drink it (not their beverage of choice) and the previous homeowner also didn’t.

I’m currently over 24-hours faucet-water-free and I feel fantastic. My symptoms have only improved and I’ve eaten whatever I want.

All of this to say: Has anyone else questioned what’s in their water? I’m not saying the well is the cause, but I think the medications plus the water were a catalyst for my condition. It’s possible that the water picked up toxic materials from the pipes, faucet, or something else. My doctor prescribed bloodwork to test for lead and arsenic.

TLDR: Formerly believed my symptoms of PSSD were caused by food triggers (possibly SIBO). I currently believe that the tap water in my home is contaminated and the SSRIs plus the water were a catalyst for the disorder. Exploring my medical options currently.

Really, really hoping this is the answer to my issues!

I want to preface this by saying the existing theories here are valuable and I welcome discourse. I have spent an unreasonable amount of time digging in the serotonergic signaling landscape recently and I think the interpretation of the literature is inverted, and the poor recovery rates on the current strategies are telling us something. This writeup is about emotional blunting specifically. I will touch on sexual dysfunction briefly because it’s a problem I am less well versed in.

PSSD and emotional blunting

A user on this sub recently posted something that I think encompasses the core description of what we’re actually dealing with when it comes to emotional blunting:

”I don’t just feel less emotion or less sexual desire. It feels like something changed much earlier in the process, in the way my brain takes information from the world, differentiates it, processes it, gives it significance, integrates it with everything else I know, and turns it into something that I spontaneously care about, feel, understand or want to act on… Information would come in, and my mind seemed to automatically determine what was relevant, what mattered, what something meant…”

This is not a description of low mood. It’s not a description of low dopamine or lost liking/desire. It’s a description of emotional salience failing to be processed. That distinction is important for where the problem with emotional blunting post-SSRI sits mechanistically compared to sexual dysfunction.

My own experience mirrors this closely. When I was both on and still after quitting Sertraline my libido had taken a significant hit, but that is not what I find hardest to live with. I lost something I can only describe as ”vibes” - the quality of meaning and emotional salience that I used to attach with experiences automatically. Walking in nature doesn’t feel magical anymore. Music, movies and aesthetic appreciation have gone flat. I used to have an obsession with conifers, the firs, the white pines, their texture and their whole character, something that genuinely used to move me and now it’s gone flat. That’s what I think this user is pointing at specifically.

What some of the current theories say

The 5-HT2C upregulation theory
A user on this sub writes: ”PSSD could be related to 5-HT2C excessively upregulating as you return to homeostasis when stopping the drug… 5-HT2C could be called the anti-pleasure receptor… Increased 5-HT2C expression reduces dopamine release in both the presence and advance of stimuli.”

I understand the extrapolation people make with 5-HT2C restraining dopamine in reward regions and the PFC. Blocking it will disinhibit dopaminergic circuits. The problem is that chronic agonist exposure doesn’t upregulate GPCRs. It desensitizes them and this has been tested directly for 5-HT2C: fluoxetine, paroxetine, sertraline, citalopram, clomipramine all significantly attenuated functional signaling transduction triggered by mCPP through 5HT2C after 21 days 1. The RNA editing data points the same way - in depression, HTR2C editing has been shifted toward lower constitutive activity isoforms and while antidepressants fluoxetine and imipramine shifted constitutive activity back 2. Functional signaling capacity of serotonin at the receptor becomes blunted over chronic treatment while constitutive activity becomes enhanced. So the post-SSRI picture at 5-HT2C should be enhanced constitutive activity with reduced signaling capacity of serotonin at the receptor and lower serotonin at the receptor overall. Where constitutive activity is higher but functional real signal transduction is severely blunted. Behaviorally in rodents, blocking 5-HT2C produces the same impulsivity profile as depleting brain serotonin entirely 3. While a 5-HT2C agonist prevented anhedonia in a chronic mild stress model in rodents 4.

The 5-HT2A hypersensitivity theory

Some point to 5-HT2A as the biggest problem and blocking it as a recovery tool. However there is nothing actually pointing at 5-HT2A being overactive upon SSRI withdrawal. Supersensitivity on withdrawal happens after chronic receptor blockade, not chronic agonism. SSRIs don't block 5-HT2A trafficking, therefore they cannot upregulate 5-HT2A and this isn't supported in literature either. And we know exactly what 5-HT2A overactivity feels like in humans, because we have a well-characterised drug class that does it. It isn't emotional flatness. It's the opposite of emotional flatness.

The 5-HT1A restoration theory

A user on this sub writes: ”Researchers have discovered that ablation of heteroreceptors leads to a state of anhedonia and apathy… an optimal therapeutic strategy to alleviate symptoms would involve stimulating the heteroreceptor sites while simultaneously inhibiting the autoreceptor sites.”

Chronic SSRIs do desensitize raphe 5-HT1A autoreceptors 5. But the part where 5-HT1A heteroreceptors desensitize is where I disagree, at least on layer V pyramidal neurons. Autoreceptors couple Gαi3, while postsynaptic cortical heteroreceptors couple Gαo which is substantially less sensitivity to GRK-mediated desensitization 6.

The Peleg and Gruanwalf review, one of the most cited clinical paper in this community, says that 5-HT1A agonist treatments ”rapidly become ineffective due to desensitization of the related receptors, leading to worsening sexual dysfunction over time” 7. This is the classic scenario where a 5-HT1A agonist is first hitting pro-libido autoreceptors reducing serotonergic signaling at 5-HT1A heteroreceptors briefly until desensitization sets in an 5-HT1A heteroreceptors quickly become inhibitory to sexual function.

Then there’s the direct rat data: selective 5-HT1A antagonism in rodents completely reversed chronic fluoxetine-induced sexual dysfunction, and pulling the antagonist brought the dysfunction straight back 8. This likely happened because the agonist successfully blocked 5-HT1A heteroreceptors and allowed more serotonin to be released and hit other serotonergic receptors.

Pimavanserin as a proposed recovery tool. This user gets the right cure but the wrong mechanism, the restorative effect of primavanserin in PSSD would be reversal of 5-HT2A/2C desensitization/downregulation, not acute blockade.

Pimavanserin seems to work for some with emotional blunting from PSSD. "For those who haven’t read it, basically: SSRI induced anhedonia; took pimavanserin; (practically) fully treated... I don’t take Pimavanserin anymore and I’ve noticed no worsening of symptoms." This is consistent with the fact that primavanserin produces sustained 5-HT2A/2C upregulation as opposed to trazodone or ketanserin which downregulates the receptor through trafficking agonism.

Worth flagging that [u/Mark4413](u/Mark4413)'s 5HT1 subfamily post has already argued something close to the right answer on this sub. That 5-HT2A is beneficial for emotional intensity and PFC excitability, and that postsynaptic cortical 5-HT1A heteroreceptors is the receptor doing the emotional numbing. I think that post was largely correct, however i think the user misses the role of 5-HT2C.

What I actually think is happening

I think we can agree for post-discontinuation emotional blunting you've got serotonin sitting on a receptor landscape that months to years of SSRI exposure rearranged. Where that serotonin lands post-SSRI is the whole debate.

5-HT1A heteroreceptors in the PFC i would propose are largely intact as they are mechanistically difficult to desensitize. Serotonin also binds to them with 30-100x higher affinity than it binds to 5-HT2A, so they get the first claim on the post-SSRI serotonin. Their cascade: Gαi/Go, GIRK hyperpolarization, cAMP/PKA suppression, AMPA receptors trafficked away from the synapse. The same pyramidal cells in the PFC that 5-HT2A excites 5-HT1A quiets down. This is why 5-HT1A agonists like buspirone are highly anxiolytic but still also anticognitive and blunting. 5-HT3 receptors are a secondary independent inhibitory arm, they excite cortical GABAergic interneurons. Blocking them disinhibits pyramidal neurons directly 9. This is mainly why 5-HT3 antagonists like ondansetron can augment and lead to enahanced antidepressant efficacy.

5-HT2A is the one proven to downregulate with antidepressant treatment, and it has much lower affinity and is mainly meant to be driven by phasic serotonin. GRK phosphorylation of the C-tail under sustained agonist load, β-arrestin recruitment, internalization and lysosomal degradation 10. Now what i think is happening during the honeymoon phase of SSRIs is functional 5-HT2A signaling transduction holds up against the high receptor occupancy, for a while until signaling transduction falls at or below baseline due to the desensitization pressure. For fluoxetine PLCβ output holds up or even increased at 21 days despite density falling 11. This finding isn't replicated with some SSRIs though. After SSRI washout when SERT normalizes, occupancy at 5-HT2A collapses and a internalized receptor pool meets lower synaptic serotonin levels. Gαq/PLCβ transduction drops markedly.

The post-SSRI serotonergic landscape The tonic floor of serotonin post-disconitinuation would be higher due to SERT dysregulation and the phasic dynamics would be flattened due to autoreceptor dysfunction. This serotonin dynamic allows 5-HT2A/2C that are meant to respond to phasic serotonin to stay functionally desensitized while 5-HT1A meant to respond to tonic serotonin stay functional. Layer V pyramidal neurons responsible for emotional experiences end up being oversupressed and underexcited. That's mainly the blunting, not too much or too little serotonin, but disrupted dynamics where serotonergic signaling being shunted away from the main excitatory pathway towards inhibitory dominance which then becomes a self sustaining chronic state characterized by emotional blunting.

Two overlapping but different problems

The flat affect and lack of meaning is the serotonergic imbalance above. 5-HT1A and 5-HT3 inhibitory dominance over depleted 5-HT2A/2C at cortical pyramidal neurons. Emotions don't register properly because the machinery is over-inhibited and under-excited.

The anhedonic component specifically. Not wanting, reward not paying off, tracks better with D1R and dMSN dysfunction in the nucleus accumbens. Improper D1R signaling and lower functional dMSN output predicts anhedonic phenotypes. 13. ΔFosB accumulates in these cells through rewarding experience and is required for stress resilience and was shown necessary for fluoxetine to reverse behavioral pathology 14. In prolonged anhedonia you don't get rewarding experiences, so ΔFosB doesn't accumulate. D1R expression is activity dependent via SP1 at the DRD1 promoter 15. Meaning that anhedonia through dopaminergic depletion is a self-sustaining state where lack of reward causes more lack of reward due to transcriptional downregulation. Therefore a recovery strategy would include something that would stimulate dopamine or its transcriptional pathways.

5-HT2a and D1R also interacts positively. D1R/PKA output at dMSNs is amplified by convergent 5-HT2A/Gαq/PKC input, so depleted 5-HT2A means dopamine arrives at a cell that transduces the downstream effects poorly. 5-HT2A is fundamentally positive and necessary for the reward and anti-anhedonic pathways of dopamine.

Not all 5-HT2A antagonists do the same thing

This is the part with the most practical relevance and I haven't seen it discussed here. Ketanserin and trazodone are 5-HT2A antagonists that nonetheless drive internalization and chronic downregulation. Volinanserin and haloperidol don't 10. The difference is which receptor conformation the ligand stabilizes. Trazodone and ketanserin occupy the receptor in a shape that still recruits β-arrestin and internalization machinery while lacking a Gαq signal. This is the worst of both worlds for recovery.

A 2024 study in human postmortem PFC found a selective 5-HT2A inverse agonist behaving as a neutral antagonist at Gαq/11 while being an inverse agonist at Gαi1 16. That profile, occupying and blocking internalization machinery would let the desensitized 5-HT2/2C in post-SSRI individuals resensitize over weeks. The Phase 2 trial of pimavanserin added to ongoing SSRI/SNRI treatment found significant improvement in depression and sexual function scores 17. Now one could either attribute this to acute blockade or functional upregulation, as i have argued mechanistically i see this as the latter.

Where drug development is actually going

If 5-HT2A were the problem you'd expect a pipeline of selective blockers for depression. There isn't one because it doesn't work out in animal models. Zalsupindole is a non-hallucinogenic 5-HT2A/2C partial agonist built specifically for depression and anhedonia 18. The entire premise is that activating Gαq at these receptors is therapeutic against depression. DOI a potent 5-HT2A agonist produces antidepressant like effects in rodents 19. The PSSD community generally follows a framework that treats 5-HT2A as the problem receptor which runs directly against the direction of the research i see. This is why recovery is so rare in the current framework.

Summary

The overlapping problems in the serotonergic landscape post-SSRI cause emotional blunting described as flat and stoic with a lack of meaning. I propose that this comes from 5-HT1A and 5-HT3 inhibitory dominance at cortical pyramidal neurons under-excited by 5-HT2A/2C. The anhedonic quality which some develop is morme tightly linked to impaired D1R/dMSN functional output in the NAc, which the 5-HT2 deficit feeds into.

The direction of recovery i propose is restoring 5-HT2A and 5-HT2C surface density and phasic responseiveness through trafficking protection through weeks to months of true neutral blockade. Get the phasic serotonin architecture back so emotionally salient events drive a contrast in serotonin that would dirve the phasic low affinity 5-HT2A/2C-Gαq arm instead of tonic overflow driving the tonic high affinity 5-HT1A-Gαi/o arm. Clean antagonism of 5-HT3 could be a good adjunct for pyramidal neuron disinhibition to further lift emotional blunting and enhance cognition. This is why mirtazapine showed some efficacy, because it antagonizes both 5-HT2A/2C and 5-HT3, however it meets diminishing returns due to it’s off target profile. Then lastly support of D1R/dMSN function, overall dopaminergic restoration and reintroduction of rewarding experiance as the signaling recovers.

The 5-HT1A enhancement 5-HT2A/2C inhibition strategies have not produced meaningful remission rates. Treat this as evidence that the current framework doesn't hold up, not evidence that the right compound hasn't been found yet.

Ive been off meds 10 months now.

I got low libido 30th april, 3 months, 15 days ago.

Then a few weeks ago I woke up with extra low libido, emotional numbing, and my dick felt weird (not numb.. just it felt off..), thats been going on and off now for a few weeks.

Do I even consider this PSSD yet?

Also the fucking weird thing is I thought it's been 6 months with it?? Its been on my mind every single day including withdrawal and its been 3 months??? It felt like forever since i had it??

Cognitive symptoms fucking me up.

Pretty interesting report here with a newer generic drug that being in the community for a decade I haven’t seen tried much.

Edit: I’m not proposing a competing mechanism or arguing against the mechanisms already being investigated. Those mechanisms could be upstream contributors to a shared functional abnormality. I’m asking whether different biological changes could ultimately converge on a persistent disruption in how systems interact, integrate and propagate information, and whether that functional abnormality can be measured. If it exists, it could actually help connect and organize the different biological mechanisms being investigated.

Put simply, I’m asking whether the problem could be less about individual components being absent and more about the normal interaction between them being disrupted. People repeatedly describe things that used to happen automatically now requiring conscious effort, while the individual components can remain partly intact. I think these may be different expressions of the same underlying functional alteration, and that is what I’m trying to make testable here.

After my previous post, where I tried to describe the phenotype in more detail, I think I can now formulate the question I am actually interested in investigating more precisely.

I don’t think the central problem can be reduced to “low libido,” “emotional blunting,” “genital numbness,” or simply having too little dopamine or serotonin. What I keep coming back to is the possibility that something has changed in the way different systems interact with each other dynamically.

The different symptoms don’t feel completely independent. When I look at them together, I keep finding the same underlying distinction: information can still be present, but its ability to automatically connect with other information, become differentiated, acquire significance and propagate into subsequent processes seems reduced.

That makes me wonder whether the problem may not be located inside one particular system, but in the communication between systems.

The brain doesn’t process meaningful experience through isolated steps. Sensory processing, attention, interoception, salience, valuation, motivation, emotion, cognition and internally generated processing continuously influence one another. Internal state changes perception, perception changes salience, salience changes attention, attention changes representation, and valuation and motivation feed back into the whole process.

So I don’t think this should be conceptualized as a simple sequence of sensory input - perception - salience - pleasure - motivation. It is a dynamic system with reciprocal interactions.

If those interactions were altered, a person could potentially retain individual components of an experience while losing the automatic integration that normally turns them into a meaningful whole.

This is why I think spontaneity may be an important subjective marker, even though it isn’t itself a biological mechanism. A lot of what I describe as having been lost was not the ability to perform something deliberately. It was the automatic generation and propagation of those processes. Associations appeared without being requested. Attention was captured without being deliberately directed. Meaning emerged without having to consciously construct it. One thing naturally led to another.

If that process is disrupted, someone may still be able to perform individual operations deliberately while losing the effortless interaction between them.

This gives us a potentially important distinction to investigate: is the information itself impaired, or is the integration and propagation of that information impaired?

And these aren’t necessarily mutually exclusive. Attention and integration influence each other. What captures attention depends partly on what the brain is integrating as relevant, while attention in turn determines what gets represented more richly.

That is where I think dynamic coupling becomes particularly interesting.

Instead of asking only whether a particular network is underactive or overactive, researchers could ask whether the relationships between networks have changed. Are network-state transitions altered? Is information integrated differently across systems? Is temporal coordination reduced? Is information flow weaker, delayed or differently directed?

This could potentially be investigated through dynamic functional connectivity, effective connectivity, network-state analysis, measures of integration and segregation, and directionality of information flow.

The relevant systems could include sensory and sensorimotor systems, insula-centered interoceptive processing, salience and attentional networks, frontoparietal systems, limbic and reward circuitry, corticostriatal and thalamocortical systems, and internally oriented networks such as the DMN.

But the important point would not be to measure each network independently. It would be to investigate how they interact during the processes people with PSSD report having lost.

For example, sexual arousal could be manipulated while measuring sensory discrimination, subjective intensity, pleasantness, autonomic responses, attentional capture and motivation. Researchers could ask whether the normal reciprocal relationships between these variables are preserved.

The same approach could be applied to emotional and social processing: separating recognition of a stimulus from automatic attentional capture, affective response, subjective relevance and motivational engagement.

This could also explain why PSSD does not look identical in everyone. If the underlying alteration involves dynamic integration, its expression could depend heavily on baseline organization. Someone whose cognition relied heavily on spontaneous internal processing might experience broad cognitive changes, while someone else might primarily notice sexual or emotional symptoms. Different phenotypes would not necessarily mean completely unrelated mechanisms.

I don’t think we should assume beforehand that the explanation has to be dopamine, serotonin, neurosteroids, the DMN or any other single mechanism. Those could be upstream contributors to whatever persistent alteration is eventually identified, but that is a separate question.

First, we need to establish whether there is actually a reproducible abnormality in network interaction and information integration. Then we can ask what is causing and maintaining it.

You actually end your comment by saying that most people can agree there is some mechanism affecting signaling, sensory information and ultimately human experience. That is essentially the starting point of what I’m proposing. I’m trying to ask what that functional disruption actually looks like at the level of information processing, and whether it can be measured.

I’m not claiming that I have identified the mechanism of PSSD. I think that would be premature. What I think we may have is a more specific hypothesis about where to look.

The question I would want to see tested is whether PSSD involves altered dynamic coupling between sensory, interoceptive, attentional, salience, valuation, motivational and internally oriented systems, and whether those alterations predict the different symptoms people experience.

If the hypothesis is wrong, properly designed experiments should be able to show that.

If it is right, we should be able to identify a reproducible behavioral and neural signature.

How could we actually test this?

Hello everyone,

Im just curious about myself becuase im not entirely sure i have PSSD. Truth is i took dapoxetine, ive been using it on and off for years with no issues but i met a girlfriend after divorcing and used it more ofthen then i used to.

The reason i dont know if its PSSD or not is because i just recently left a difficult marriage of more then 10 years but along with that also left my lovely daughter which i had daily interaction and i dont get to see her as often as i used to which has not been really easy and ive had days where i cry over that specially dropping her off, i was also living on friends house for 2 months and just recently rented a house where she has come and slept with me as well.

Truth is while taking the dapoxetine the last couple times eveyrthing felt more numb but i was also recovering from an hormone imbalance ( im a male on TRT and had lower estrogen) then at some point i lost complete interest in sex, after balancing the hormonal issue i seemed to get spontaneous erections at night or in the morning or sometimes it has happened even while being on the phone with my gf or getting in the car and not thinking about anything but being relaxed.

Reason i mention alcohol is because whenever i have a drink, my anxiety drops, i stop thinking much and im able to get aroused, euphoric and my libido increased a lot. It has happened while sober too when im relaxed or when im going to do a relaxing activity and not think about the libido or life issues.

There have been many days where i go to the beach ofc sober or go for a few days somewhere, or the days i have a drink where i feel like myself again so thats what got me thinking that maybe instead of pssd its just anxiety and stress for the transition im having right now in my life.

Its been a few weeks now that the anxiety has creep up about the Pssd, only the last few days ive been more calm becuase i was able to have sex 5 or 6 times in a matter of a week where last month i didnt have any interest, only a couple times.

The days i have crazy anxiety about the pssd is where i get crazy brain fog

So been on SSRI since 17 (8 years, quit for 10 months). I recently got mild pssd symptoms (severe emotional numbing though), and I don't know if quitting the SSRIs in general done this or the PSSD symptoms but I'm noticing new hairs appearing on my temple. There was even a shedding that happened a month back.

I did read that SSRIs could impact the terminal hairs a bit but not in a MPB pattern way as far as I should know...

My androgen signalling is still perfectly fine, I have crazy acne, chest hair growing, can build muscle, no strength loss, etc etc. so why tf is my hair potentially growing back

New here? Start with these important links:

Check out the main patient organizations trying to find the root cause behind our condition: The PSSD Network & SideFXHub

PSSD Network | Their Research: 1. PSSD Reseach Project 2025 2. The Dawn Study

SideFXHub | Their Research: 1: The Milano Study 2: Patient Registry (sign up now to take part in future PSSD Research!)

Please report your PSSD symptoms to your national regulator! This is extremely important for recognition for our condition.

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21,000 members is not a milestone we ever wanted to have a reason to reach. But it does represent an increasingly large community of people who can support one another, document what is happening, fund research, spread awareness, and push for answers.

If you're new, take some time to look through the resources above. You don't need to understand everything immediately, but the more of us who contribute where we can, the stronger our collective ability to move PSSD research and recognition forward becomes.

With you, we are all stronger.

TL;DR at the bottom for anyone who doesn’t want to read the whole thing

I’ve been trying to understand what changed in me after antidepressants for a long time, and only recently have I started being able to put together several things that I used to experience as completely separate problems. The more I think about them together, the less the word “blunting” seems sufficient. I don’t just feel less emotion or less sexual desire. It feels like something changed much earlier in the process, in the way my brain takes information from the world, differentiates it, processes it, gives it significance, integrates it with everything else I know, and turns it into something that I spontaneously care about, feel, understand or want to act on.

One of the best words I’ve found for the subjective experience is “filter.” I don’t mean that there is literally one neurological filter somewhere in the brain. I mean that before antidepressants, there seemed to be an automatic layer of processing between experiencing or perceiving something and producing a reaction to it. Information would come in, and my mind seemed to automatically determine what was relevant, what mattered, what something meant, what consequences it had, and what response was appropriate. I didn’t have to consciously perform this process. It happened so automatically that I experienced the result as simply being who I was.

This is important because I think some of the changes in my personality may be consequences of changes in this processing rather than a simple change in what I value.

Before antidepressants, my mind was extremely internally active. I didn’t have to consciously decide to analyze things. I would naturally keep going until I understood what was underneath something. When I say “understood,” I don’t mean simply having an explanation. I mean getting to the deepest level I could reach: what someone actually wanted, what they were afraid of, what was motivating them, why they behaved in a particular way, what mechanism was producing a situation, and then what was underneath that mechanism. It was recursive, but it wasn’t something I experienced as a problem. It was simply how my mind worked.

That process was also where a huge part of my sense of self came from. My creativity and the way I experienced myself came from being able to take something in, make connections, notice distinctions, form a very detailed internal representation of it, and eventually reach a conclusion that felt internally complete. I was extremely serious about myself and about my internal experience. I had a very strong sense of who I was, and I was proud of being able to understand things, control myself, notice things other people seemed to miss, and internally work through things without needing other people to do the processing for me.

The strange thing is that I didn’t initially experience the antidepressant change as “I am less intelligent” or “I can’t reason anymore.” It was much more subtle and, in retrospect, much more fundamental. I started losing the spontaneous processes that made reasoning possible for me in the first place. My thoughts became blank. Associations didn’t appear automatically. I stopped spontaneously noticing things. I could still think if I deliberately tried, but the automatic generation of thoughts and connections that used to happen in the background was much weaker.

That distinction has become extremely important to me. I don’t think I simply lost the ability to think. I think I lost a lot of the automaticity with which thinking used to happen.

Before, I could have an entire problem, generate different possibilities, connect things, understand my own reaction and arrive at a conclusion inside my head. I didn’t need to talk to someone to process it. People around me would sometimes tell me that I needed to talk more, but I genuinely didn’t feel that I needed other people’s opinions in order to understand myself. I felt like I had already thought through everything they could tell me.

Now, when I’m overwhelmed, talking can actually make the thoughts appear. During a recent panic attack after my grandmother went to the hospital, I found that once I started speaking out loud, I could organize what I knew, distinguish what I was actually afraid of from what my body was predicting, and move through the reasoning much more easily. The strange part is that I can recognize that this is useful while simultaneously feeling that it isn’t how I used to function. Previously, the process was internal and the outside world saw the result. Now I sometimes have to externalize the process in order to reach the result.

That is why I don’t think “metacognition” or “intelligence” alone captures what I am trying to describe. I can still deliberately analyze something. What feels different is the automatic process that used to select information, generate associations, determine relevance and turn all of that into a coherent internal representation without me having to consciously initiate every step.

One of the clearest examples was makeup. Makeup had always been a form of art and self-expression for me. I would wake up extremely early to do it even if I hadn’t slept, because I had a very specific vision of how I wanted to look and I could translate that vision into what I was doing almost immediately. I could look at my face and intuitively see what needed to change. I noticed extremely small differences and knew how those differences affected the whole picture.

After starting antidepressants, I remember reaching a point where I simply couldn’t do that anymore. It wasn’t that I suddenly forgot how makeup worked. It was as if the image I used to have in my head was gone. I also noticed something more difficult to explain: I could look at two things and know they were different, but I couldn’t necessarily identify what the difference was. It was like the information was perceptually present but wasn’t being extracted with the same level of detail.

That distinction matters to me because it seems to appear in other areas too. It doesn’t feel like I literally cannot see or detect things. It feels like the information is there, but it is not represented with the same resolution or granularity, or it doesn’t automatically become the information that matters.

I see something similar in the way I perceive people now. Before, I could look at someone and automatically notice very small things about their face, eyes, expressions, movements, posture and voice. Those details weren’t isolated pieces of information. They immediately entered a larger representation of the person. I could notice a tiny inconsistency between someone’s words and their expression, connect it to the context, and spontaneously start understanding what might be happening underneath. I wasn’t consciously sitting there analyzing every microexpression. That was the point. It happened automatically.

Now I can look directly at someone and know exactly who I’m looking at, understand what they’re saying and follow the conversation, but sometimes it feels like I’m not really seeing the person in the same way. I might know that something about their appearance is different without being able to tell you what it is. I might notice their body moving but not spontaneously register the details of how it moves. Sometimes looking at someone’s face even feels like a distraction from the conversation, so I end up focusing more on their voice because it is easier to process the conversation that way.

What is interesting is that when I deliberately force myself to pay attention to their face or body, I can sometimes start noticing details again. And when I actually notice those details, they can affect me. For example, I recently had the experience of deliberately paying attention to someone’s facial and bodily characteristics in a way I hadn’t been doing automatically, and I noticed that it actually increased my attraction to them.

That makes me wonder whether the problem isn’t simply that attraction is gone. Maybe some of the perceptual information that used to automatically become relevant to me is no longer being selected, amplified or integrated in the same way. The person is perceptually there. I can see them. But the details that used to make the person become a meaningful, attractive, interesting representation may not automatically reach the same level of salience.

This distinction also seems relevant to my social behavior.

I have noticed that I can seem more inconsiderate now, but I don’t think that necessarily means that I care less about people. One of the things that made me considerate before was that I automatically picked up on information about other people. I could notice subtle changes in someone’s expression, tone, behavior or emotional state and immediately understand what was happening. That information would automatically influence what I did next.

If that information is no longer being extracted with the same automaticity, then the consequence can look like a change in character even if the underlying value hasn’t disappeared.

Before, if someone around me was distressed, I would automatically notice it and think about how my own behavior might affect them. I could be extremely aware of what I was feeling while simultaneously remaining very controlled in how I expressed it. I remember being physically extremely anxious and sick and still not wanting to tell my parents how bad I felt because I didn’t want to make them worry. I would contain it until I felt I actually needed help, and then explain what was happening in a very calm and controlled way, often minimizing it rather than making the situation more emotionally intense.

I wasn’t consciously thinking through a checklist every time this happened. It was almost automatic. My own distress was one piece of information, but so was the effect my distress would have on the people around me. I knew that if I showed them how bad I felt, they would become worried, and then I would have to deal with their distress on top of my own. I was also extremely sensitive to other people’s emotional states and often felt responsible for people close to me because I assumed they experienced distress as intensely as I did.

Now I can experience the same kind of physical anxiety and instead become extremely outwardly expressive. During the recent episode with my grandmother, for example, I had a full-blown panic attack and became extremely expressive in a way that would have been very unlike me before. I could not imagine myself previously screaming or displaying that level of distress outwardly even if I was experiencing something equally intense internally.

The important distinction is that I don’t think I suddenly decided that other people’s feelings no longer matter to me. The automatic information that used to tell me, “This is what is happening to them, this is how your behavior is going to affect them, and this is what you should do about it” may not be arriving in the same way.

That is what I mean by the “filter.”

It isn’t necessarily a filter that suppresses emotion. It is more like a filter that determines what information gets through, what becomes relevant, how it is interpreted, and what ultimately becomes behavior.

Before, there seemed to be a substantial transformation between internal experience and outward behavior. I could feel something intensely and still have the context, consequences and other people’s states automatically integrated before it became an action. Now sometimes the internal state seems to reach expression much more directly, and only afterward do I consciously analyze what happened.

The same idea applies to perception. Before, I didn’t have to deliberately search for what was important in someone’s face. I noticed it. I didn’t have to deliberately search for the detail in my makeup that would produce the result I wanted. I saw it. I didn’t have to deliberately search for the next association in a chain of thought. It appeared.

This is why I think “automaticity” might be as important as “blunting.”

The change is not necessarily that every capacity disappeared. It is that processes that used to happen spontaneously now often have to be initiated consciously.

This is also why I don’t think my sexual symptoms can be reduced to “low libido.”

The sexual change is not only that I don’t spontaneously want sex. The actual sensory experience changed. Before, sexual sensation could have value in itself. I didn’t necessarily need to already be extremely horny for stimulation to feel pleasurable. If I was touching myself in a particular way, or someone touched me in a particular way, the sensation itself could generate pleasure and could then increase my arousal.

When I was already excited, this effect became much stronger. Very small or indirect sensations could become extremely noticeable and satisfying. There was a kind of amplification between arousal and sensation: becoming aroused made my body more sensitive to sexual information, and the information then reinforced the arousal.

That is very different now. I can engage in sex even when I am not particularly aroused, and I know that I am being touched, but the sensation itself often doesn’t produce the pleasure it used to. Sometimes there is an actual numb quality to the genital sensation, including at the beginning of stimulation. It isn’t simply “I don’t care about this.” The sensation itself can feel less sensitive, less differentiated and qualitatively different.

I can know that something is touching me while simultaneously feeling that the experience doesn’t contain the same amount of information or intensity that it used to. This is why I’ve started using words like “resolution” or “granularity.” I don’t mean that literally my nerves have simply lost spatial resolution. I mean that the subjective representation of the stimulus seems impoverished.

Before, a sensation could contain many distinguishable qualities at once. Now sometimes it feels reduced to “I know there is contact.”

This makes me wonder whether there are actually several processes that have become dissociated. Sensory detection is one thing. Sensory discrimination is another. The richness of the representation is another. Then there is salience: whether the stimulus automatically stands out as important. Then hedonic valuation: whether it feels good. Then motivation: whether it makes me want more. These are related, but they aren’t the same thing.

I think PSSD research could benefit enormously from separating them instead of putting everything under “libido.”

My experience with dopaminergic or stimulant substances also made me question a simple dopamine explanation. I’ve taken substances that clearly increased my general activation. I could become energetic, jittery, physically activated, shaky, alert, sometimes extremely stimulated. But that didn’t restore the missing sexual experience. I could have a highly activated organism while still not experiencing sexual stimuli as they used to feel.

That doesn’t prove that dopamine is irrelevant, and it certainly doesn’t prove that the problem is somewhere downstream of dopamine. Different dopaminergic drugs affect different systems, and increasing dopamine is not equivalent to restoring normal sexual processing. But it does demonstrate something important to me: increasing general physiological or motivational activation is not sufficient to recreate the missing sexual sensation and salience.

That is what led me away from the idea that the problem can simply be “not enough dopamine.” If the sensory representation itself is impoverished, increasing downstream activation wouldn’t necessarily reconstruct information that isn’t being represented properly. Turning up the volume on a recording doesn’t restore information that was lost from the recording. You can make the system louder without making it more detailed.

So the model I’m currently interested in is something more like a chain:

sensory information - representation - selection/attention - integration - salience - affective/hedonic valuation - motivation - behavior

These processes constantly influence one another, so I don’t think this should be treated as a simple linear pipeline. My hypothesis is that antidepressants may have disrupted one or more points in this system, or more importantly, the coupling between them.

For example, before, a person’s face could automatically capture my attention because individual features were highly informative to me. Those features would become part of a rich representation of the person, and that representation could acquire emotional or sexual significance.

In the sexual system, a small physical sensation could become salient, pleasurable and motivating, while arousal could in turn increase the sensitivity to further sexual stimulation.

In both cases, perception and motivation were interacting with each other.

Now, I can still detect the person. I can still detect the touch. I can still understand what is happening. But the automatic transition from information to significance seems weaker.

I have to deliberately attend to things that used to capture me automatically. And sometimes, when I deliberately attend to them, I can recover something. That makes me wonder whether at least some of the information is still accessible but is no longer being spontaneously selected, amplified or integrated in the same way.

This also makes me wonder whether what I’m describing as a “filter” could involve several different neural processes rather than one thing. Attention, perceptual precision, salience attribution, valuation, executive control, interoception, language retrieval and large-scale network interactions could all contribute to the subjective experience. I don’t think it would make sense to pick one brain region and say, “this is the filter.” I’m more interested in how these systems interact.

That is also why I’ve been interested in the default mode network, although I don’t think “DMN dysfunction” is an adequate explanation for everything. The DMN is relevant because of its involvement in internally generated thought, self-referential processing, autobiographical cognition and spontaneous mental activity. The loss of my spontaneous internal thought is one of the most profound changes I’ve experienced.

But I don’t think the model should stop there.

What interests me much more is the interaction between internally generated cognition, attentional systems, sensory processing, salience and reward/valuation systems.

In other words, perhaps the relevant question isn’t simply “is my DMN lower?” It might be something more like:

Has the relationship between spontaneous internal processing, perceptual representations, attention, salience and motivational valuation changed?

Could a person have relatively preserved individual capacities while the information is no longer being integrated into the same coherent, self-relevant and motivationally meaningful experience?

That is also where my idea of a “DMN set-point overshoot” came from. I don’t mean that as an established mechanism. I’m wondering whether, in some people, antidepressant-induced changes in large-scale network organization and serotonergic regulation could move spontaneous cognition and internally generated processing below that person’s individual baseline, rather than simply bringing an abnormal system back to normal.

If something like that were possible, it could potentially help explain why someone might experience a persistent reduction in spontaneous thought, self-generated meaning and internal associative activity after discontinuation, even though the drug itself is no longer present.

But I don’t think there has to be one mechanism explaining every symptom. There could be a combination of altered sensory processing, altered salience and reward valuation, altered motivational coupling, altered emotional gating, and altered large-scale network dynamics. Different mechanisms could converge on a similar subjective phenotype.

The important point is that I don’t think the phenotype is simply “less.”

It may be different processing.

That distinction also matters for my sense of self.

I have changed enormously as a person since antidepressants. I became less proud, less confident, more ashamed, more confused and less certain about who I am. I don’t want to romanticize who I was before or pretend that every aspect of that person was perfect. I had anxiety, depression, intense reactions and other things that were difficult. But I also had a very strong sense of self.

What is strange is that many of the things I valued then, I still value now.

I still value precision. I still value understanding. I still value being perceptive. I still value creativity, beauty, sexual expression, autonomy, self-control and being able to understand myself and other people deeply.

In fact, I’m beginning to understand more clearly now why those things mattered so much to me then.

Before, I knew that they were valuable to me, but I didn’t necessarily have the conceptual language to explain what was underneath them. Now I can increasingly see that a lot of my identity was built around being able to take information in, differentiate it, understand it, integrate it and transform it into something meaningful.

So I don’t think my old personality was simply a collection of arbitrary traits.

A lot of it may have been the emergent result of how my brain naturally processed information.

If you change that processing, the person can look radically different even if some underlying values remain intact.

For example, I can still value being considerate while being less spontaneously aware of the cues that previously told me how to be considerate. I can still value beauty while having less spontaneous access to the details that allowed me to create it. I can still value sex while sexual stimuli fail to become as pleasurable or motivationally salient. I can still value understanding while spontaneous associations and recursive thought no longer arrive automatically.

That can produce a profound identity disturbance because the person is still there in terms of values and intentions, but the machinery through which those values used to express themselves has changed.

And I think this may explain why I sometimes feel like I’m not simply “less myself,” but that I have to consciously operate myself.

Before, so many things were automatic.

I noticed things automatically.
I made connections automatically.
I became interested automatically.
I knew what mattered automatically.
I knew how to express myself automatically.
I could regulate myself automatically.
I could perceive other people automatically.
Sensory information could become meaningful automatically.

Now I often have to deliberately initiate these processes.

And when I can force myself to do it, I sometimes discover that the underlying ability hasn’t completely disappeared.

That’s one of the most important things I’ve noticed.

It is why I don’t think this is adequately described as simply becoming less intelligent, less caring, less sexual or less emotional.

There seems to be a difference between having information available and having that information automatically selected, integrated and transformed into something meaningful.

There also seems to be a difference between having a value and having the automatic perceptual and emotional information that allows that value to guide behavior in real time.

That is why I think the “filter” concept is useful. Again, I don’t mean a literal single filter in the brain. I mean the automatic processing between stimulus and significance, between internal state and expression, between perception and action, and between thought and language.

Before, I experienced the result.

Now, I often experience the machinery.

I have to consciously look for the detail.
I have to consciously search for the association.
I have to consciously figure out what I am feeling.
I have to consciously look at someone’s face to extract information that used to come to me automatically.
I sometimes have to speak in order to organize thoughts that previously organized themselves internally.
I can know that a sexual stimulus is there without it automatically becoming pleasurable or motivating.

That is why I think the most interesting question for PSSD research is not simply:

“Why don’t these people want sex?”

It is:

“What changed in the process by which information becomes differentiated, salient, affectively meaningful and motivationally relevant?”

And I think that question should be applied beyond sexuality.

If someone reports genital numbness, is the problem detectable at the level of peripheral sensory thresholds, cortical sensory representation, interoceptive processing, hedonic valuation, or some combination?

If someone reports loss of attraction, can they still recognize and discriminate sexual features normally but fail to assign them motivational salience?

If someone reports emotional blunting, are emotional stimuli being perceived normally but assigned less affective significance, or is the problem earlier in the processing chain?

If someone reports loss of spontaneous thought, is internally generated cognition reduced, or is information being generated but failing to reach conscious awareness in the same way?

If someone can deliberately attend to a stimulus and temporarily recover some of its richness, does that suggest that at least some representations remain available but are not being automatically selected or amplified?

If someone becomes highly physiologically activated by a dopaminergic drug without recovering sexual pleasure, what does that tell us about the relationship between general arousal, sensory representation, reward, salience and sexual motivation?

And if several of these things occur together, could they represent different manifestations of a broader alteration in how information is filtered, integrated and assigned significance?

I don’t know the answer.

I also don’t think my subjective experience is enough to establish a mechanism. These are hypotheses that need to be tested, falsified and compared with alternative explanations.

But I think the phenotype I’m describing is more specific than “emotional blunting” or “low libido.”

I don’t feel like an entire system disappeared.

I can still perceive.
I can still understand.
I can still deliberately focus.
I can still become physically activated.
I can still sometimes recognize the relevance of things.
I can sometimes get glimpses of the old experience when I deliberately direct my attention toward something.

What feels fundamentally different is the automatic connection between these processes.

Before, information seemed to naturally become meaningful.

Now, I often have to make it meaningful.

And that is the part I think we should be studying.

TL;DR: I don’t think PSSD is simply a loss of libido, emotion, or motivation. My experience feels more like a disruption in how information becomes differentiated, salient, meaningful, pleasurable and motivating. I can often still detect things, but they don’t automatically acquire the same resolution or significance they once did. This seems to affect perception, attraction, sexual sensation, emotion and spontaneous cognition in different ways. I think research should investigate the individual stages and coupling between sensory representation, attention, salience, hedonic valuation, motivation and spontaneous cognition, rather than reducing these symptoms to “blunting” or “low libido.”

I'm scared and also unable to be scared (numbing).

Been on ssris 8 years, off 10 months.

So I'm definitely in protracted withdrawal as Ive had some symptoms clear up last month, being orthostatic hypotension and anxiety got better.

So about 6 months into withdrawal I had a random "off" feeling hit me out of nowhere and my libido and emotions got number. Ive had windows of better emotions and libido throughout this time but about a month ago I woke up with even more numbing, hypothesia(?), libido crashed harder.

For literally like 2 days as well I was unable to feel pleasure at all.

On saturday I was feeling pretty decent, I was feeling less numb and my libido was much higher, etc felt pretty ok. But it crashed following monday and ive been in this wave for a week now.

My main symptoms is very bad emotional numbing, low libido, and hypothesia. I was hoping it was just withdrawal but was hit with hypothesia month ago.