A clinical presentation of PSSD (Made by sufferer and Neurologist)

[Dw123345]

In my 4 months of total SSRI withdrawal I’ve been sent through the wringer with very very little improvements over time. Every symptom you can think of I’ve had it. When first put into protracted withdrawal I experienced every symptom of PSSD. Some symptoms have improved in that regard, and some have not changed. Being bed ridden for 2+ months I’ve done nothing but research, and the autoimmune and immunology theories fascinate me. Since going into withdrawal I’ve had many dysautonamia symptoms which are all new to me including food sensitivities, POTs symptoms, MCAs symptoms etc, long COVID symptoms, and found this on Reddit in regards to this theory. The name of the person isn’t disclosed but it was made between a PSSD sufferer and his neurologist with experiences from other PSSD and withdrawal sufferers. It could have relevance to the people in here with protracted withdrawal. Some people end up in withdrawal significantly longer than others, some people far more severe, and some people with no withdrawal at all. Every person has a unique set of genes and immune system, and even tho time is the biggest healer, I have hope that one day something will be available to help make that time significantly reduced or nulled. The author doesn’t make a direct correlation to ssri discontinuation syndrome, but in the thread this was found in he does mention that his neurologist does believe it is relevant to those in protracted withdrawal with no PSSD symptoms as well. It’s a long read, but it’s full of good information. 
 

Introduction

 

 I've compiled a comprehensive summary to form a clinical picture of Post SSRI Sexual Dysfunction from the base of my own diagnostic process and the conversations had between me, other patients, and my neurologist. My neurologist has seen dozens of PSSD patients and considers PSSD as a serious and broad ranging neuroimmunological condition with multineural and significant brain involvement. I underline that not enough patients have gone through the diagnostic process yet for us to conclude anything definitive. It is also entirely possible that there's variables in the mechanism of the condition, as some present with varying set of symptoms. But so far in the first patients examined, there's clear similarities in biomarkers and clinical findings. It would be crucial for each patient to pursue to get clinically evaluated for their PSSD, for us to bring this condition to the light in the medical world.

 

Neuropathy

 

 Small Fiber Neuropathy has been confirmed in many PSSD patients with decrease in intraepidermal nerve fiber density using PGP9.5 immunofluorescence staining skin biopsies and abnormalities in Quantitative Sensory Testing. Corneal Confocal Microscopy (CCM) has shown abnormal nerve fiber density and increase in dendritic cells, which suggests that there is an immune system component involved in the condition. Large nerve fiber involvement has not been present, with normal Electromyography (EMG). The presentations of neuropathy are non-length dependent and include sensory deficits and abnormalities like numbness of skin, tingling and touch sensitivity. Autonomic neuropathy is present in the SFN with dysfunction in the sexual, cardiovascular & gastrointestinal functions.

Identifying the underlying cause of Small Fiber Neuropathy is crucial, as different underlying causes require different treatment approaches. Treatments are discussed in a later section.

 The biomarkers identified so far have confirmed immune system involvement behind the SFN.

Blood & CSF biomarkers vary and they're not the same for everybody, but findings among patients include abnormalities in cerebrospinal fluid e.g., elevated leukocytes and IgG index.

 Typical CSF examinations are proteins, oligoclonal bands, IgG index, leukocytes, erythrocytes, and lymphocytes. The presence of these markers in csf indicate an abnormal immune response specifically within the central nervous system. Abnormalities in Cytokine concentrations are observed in the blood, with high inflammatory cytokines e.g., Interleukins 6 & 10 or an overall imbalance in cytokine concentration. In a healthy and properly functioning immune system, cytokines are typically balanced and regulated. This balance is crucial for maintaining immune homeostasis. GPCR autoantibodies are often observed in the blood, targeting the G-proteins of the autonomic nervous system and in around 15-30% of SFN cases TS-HDS & FGFR3 antibodies are present. New biomarkers will most likely continue to emerge, particularly the field of autoantibodies is still developing.

 In simple terms, an autoimmune condition is when the body's immune system mistakenly attacks its own cells, thinking they are invaders. This can lead to various health problems because the immune system is supposed to protect the body, not harm it. With an immune-mediated process in SFN, the immune system mistakenly attacks the small nerve fibers in the skin and other tissues, leading to nerve damage, dysfunction. What's present also is brain involvement with a neuroinflammatory process.

 

Neuroinflammation & Immunology

 

Neuropathy is one piece of the puzzle in the condition but there's indeed more going on with the brain involvement, which remains the most difficult area to tackle. Cognitive symptoms include e.g., emotional numbness, anhedonia, aphantasia, loss of libido, cognitive impairment. Are signs of severe neuroinflammation and dysfunction in Dopamine & Serotonin signaling. Neuroinflammation emerging from SSRI treatment has been observed with TSPO-PET by prof. Roberto Melcangi in the university of Milan.      Neuroinflammation is one of the key components in the condition. Neuroinflammation alters neurosteroid synthesis and studies have shown that pro-inflammatory cytokines, which are molecules involved in the inflammatory response, can affect the enzymes and processes involved in neurosteroid production.

 Neurotoxicity and brain damage have long been terms used by patients to describe their condition in the community, this terminology might not be entirely correct considering the clinical presentations of PSSD. A typical presentation is windows with bettering in symptoms and crashes with worsening in symptoms even years into the condition, these are signs of immunological fluctuations occurring. Many patients also describe a fluctuation in symptoms triggered by infections, many experience changes in the frequency of contracting different infections after getting PSSD. Also notable, that the onset of PSSD can occur immediately, suddenly during a longer period of SSRI use or only after the discontinuation. It is true that an initial neurotoxic effect has had to occur with the medication to induce the condition, but a persisting and fluctuating symptomatology that can start whenever during the period of SSRI use strongly suggests persisting neuroinflammation with immune system involvement in the long run. Many patients also present with Mast Cell Activation syndrome (MCAS) which includes newly emerged food allergies and other hypersensitivities leading to the overactivation response of the immune system. MCAS is also a contributor to the cognitive dysfunction in many patients.

 The persisting neuroinflammatory symptoms could be attributed to immunology. However, it remains unclear if the dysfunction in dopamine & serotonin signaling and synthesis are secondary presentations of the larger neuroimmunological entity or if there's also other 

mechanisms at play in that area. Although the biomarkers and most of the symptoms point to immunology, a lot more research is needed to observe the mechanisms of the brain changes in more detail. What we can be hopeful about is that on immunotherapy treatment, in addition to ease in symptoms of neuropathy occuring, cognitive improvement has also occured among patients. Suggesting an immune-mediated cause behind the neuroinflammatory process.

MRI brain scans of PSSD patients come back normal. However, FDG-PET and SPECT scans would be very important to perform on PSSD patients. MRI is good at visualizing detailed anatomical structures, but FDG-PET and SPECT scans excel at providing functional and molecular information about the brain, making them particularly valuable for conditions characterized by molecular or metabolic changes. The downside is that they are hard to access.

 The first FDG-PET scan performed on a PSSD patient showed signs of temporopariental hypometabolism likely attributed to their neuroinflammation, similiar discovery to long covid patients.

 Treatment options include, but not limited to

Immunomodulatory therapies are treatments that help regulate or modulate the immune system's activity. They are used to either enhance or suppress the immune response, depending on the specific needs of the patient and their underlying condition. To get treatment approved you will need a clinical diagnosis of small fiber neuropathy diagnosis and/or evidence of an autoimmune response occurring. If the neuroinflammatory response is also immunological, cognitive symptoms could also respond to the different immunomodulatory treatments. Officially these treatments are approved for diagnosed neuropathy and other autoimmune conditions.

 PSSD patients initially trialed on and experienced temporary, but not lasting effect with Inuspheresis which is a "blood plasma purification to remove disease-causing substances and environmental toxins. By relieving the human body, Inuspheresis helps to strengthen the immune system and the body's own self-healing". Inuspheresis Update: PSSD (reddit.com)

 More potent immunomodulatory therapies than inuspheresis are necessary to see lasting change, and the first PSSD patients trialing on these treatments have experienced improvement in their symptomatology. The rationale behind using immunomodulatory therapies such as IVIG or Rituximab in PSSD is to counter the autoimmune response causing SFN, neuroinflammation among other possible complications. And to modulate the immune system's activity, reducing the autoimmune response targeting the small nerve fibers and reduce the neuroinflammatory process. It is important to note that the rate of response for treatment varies from patient to patient, others might experience rapid response and relief with milder therapies while some need more potent and long-lasting immunotherapy. The treatment with immunomodulatory therapies is not a quick fix but a up and down long 

 process personalized for each patient, though also a very potential one. A larger reference pool of PSSD patients is needed to access the true rate on response to these treatments.

Different treatment options include:

• High Dose Corticosteroids: corticosteroids, like prednisone or dexamethasone, are synthetic versions of naturally occurring hormones in the body. They work by suppressing inflammation and immune responses. Corticosteroids are commonly used to manage symptoms of autoimmune diseases by reducing inflammation and suppressing the immune system's activity.
• IVIG: Made of a preparation of antibodies derived from the plasma of thousands of donors.

It contains a diverse range of antibodies that can help regulate the immune response. It used in the treatment of various autoimmune disorders to modulate the immune response.

• Rituximab: Is a monoclonal antibody that targets a specific protein (CD20) found on the surface of B cells, which are a type of immune cell. This binding triggers cell death or depletion of B cells from the circulation. This can help greatly modulate the immune response, particularly in conditions where B cells play a significant role.

Like stated not limited to, as other immunotherapies could emerge to prove useful. BC007 being one of them often mentioned in the community.

 

End Note

 

 I believe that one day there will be recognition and published studies formally explaining the mechanisms behind the condition. With patients getting diagnosed and some on treatment trials, we might be closer than we think. What we do know already, is that SSRIs have been shown to be immunomodulatory, and alter several aspects of immune cell functioning. They bind to and act on the ACE2 receptor likewise with the spike protein of COVID19.

Symptomatically PSSD and Long Covid patients also have similarities.

 Drug induced iatrogenic conditions are a difficult subject to approach in the medical world and there's no one else speeding up the process than ourselves. The best we can do now is to get clinically evaluated and diagnosed, so that we gather as much undisputed evidence to present with as possible. This community should get organized and focus on the scientific side, instead of pondering on the management of symptoms via mediums like supplementation.

 Similar or near identical conditions are documented occurring from e.g., Finasteride, Accutane, and neuroleptic use. Perhaps one day all of these will be officially recognized in the medical world under a term such as a "post drug neuroimmunological syndrome" with readily available treatment options. What our community can do is organize up, take note of these discoveries and pursue to get clinically diagnosed.

[Fairsome]

Great work. I believe PSSD/protracted withdrawal and Long Covid share the same root causes - there were people with PSSD who have tested positive for autoantibodies against proteins G which are also present in Long Covid. I also posted another article in the PSSD topic about that. It is just sick that SSRIs were invented almost 40 years ago and we are just starting to understand a bit more how do they work and what causes their long-term effects.

[Altostrata]

Is there any evidence of inflammation in PSSD? This theory hinges on that crucial connection.

 

Any theory of PSSD would also have to apply to female PSSD.

 

FYI there's zero evidence for inflammation as a cause of psychiatric disorders. It's one of those sciencey trendy buzzwords being tossed around by psychiatry as explanation for everything. Another is "epigenetics". In my opinion, neither has any more evidence than the zillion other biopsychiatry theories thrown against the wall over the years.

 

 

10 hours ago, Fairsome said:

Great work. I believe PSSD/protracted withdrawal and Long Covid share the same root causes - there were people with PSSD who have tested positive for autoantibodies against proteins G which are also present in Long Covid. I also posted another article in the PSSD topic about that. It is just sick that SSRIs were invented almost 40 years ago and we are just starting to understand a bit more how do they work and what causes their long-term effects.

 

Could those autoantibodies be from being exposed to covid or a covid vaccination? These are quite common sources of antibodies.

 

Very unlikely that sequelae from an infectious disease share same the cause as a drug-induced condition. Overlap of symptoms means nothing but coincidence. Coincidence is not causation -- people who are fuzzy thinkers about science repeatedly make the mistake of thinking coincidence is meaningful. Theories with this flimsy basis are more appropriately discussed on reddit or PSSDforum.org, not here. Thank you.

[Fairsome]

There's an ongoing research about these theories, it is not some random assumptions from reddit or the web. Professor Roberto Melcangi and others try to look into this. No one has made much effort to understand what causes some protracted SSRI effects, anyway.

 

It is well known that SSRIs affect the immune system in a variety of ways (and the gut microbiota, too, which is involved in immune response) so it is quite possible that at least some symptoms people experience have a significant immunological component behind them. These drugs don't act on one organ or one system - they have complex effects on pretty much everything in our bodies.

[Dw123345]

I’m not entirely sure on the neuro inflammation theory, it doesn’t intrigue me as much so I didn’t pay much mind to that, but I don’t think it’s just a coincidence that the symptomology is so similar between post ssri protracted withdrawal, PSSD, and things like long covid and dysautomania are so similar. I think the immunological theory is a strong one. What other strong theory would support why someome might experience so many debilitating symptoms from one pill, or 5 pills, or 10 years of pills, and someone else the same symptoms after a dose increase, or polydrugging, or a withdrawal. Same with Covid. One person might get the sniffles and another end up in the hospital or dead. Some people get long covid and some people recover 100%. I don’t see how it could be anything other than an immune response or gene interaction, and real testing needs to be done because of the similarities in the symptoms. It’s also the only thing we have going for us that isn’t “suffer it out and hope for the best”.

[Altostrata]

It's a coincidence. If you want to discuss these theories, reddit or pssdforum.org are more appropriate venues. Thank you.