RxISK began in 2012. One of its main goals was to offer people an opportunity to report problems they had on treatments – any treatment – and generate a report they could take to a doctor in the hope this might get the doctor to take their problem seriously.
I had seen my first cases of Post-SSRI Sexual Dysfunction (PSSD) in 2000, had been writing about withdrawal since the late 1990s, was linked to suicide on SSRIs since the late 1990s, and everyone knew SSRIs interfered with sex. Still it came as a surprise that among the commonest reports of any problem on any drug to RxISK were of PSSD problems, along with post-finasteride (PFS) and post-retinoid sexual dysfunction (PRSD).
Within two years we were able to get an Article on 120 cases published and a few years later an article on 300 cases and we now have over 1000 reports on PSSD, PFS, PRSD or PGAD – See PSSD Literature page.
Brain and Body
The word antidepressant immediately conjures up an image of a brain but there is very little serotonin in the brain. Take an SSRI pill and the immediate effects are to feel nauseated and to have numb genitals – although not everyone notices either the nausea or the numbness.
Could the problem be peripheral? In the skin, or sensory nerves especially a group of small c-fibres, which seem linked to caresses rather than just the mechanical or other aspects of touch? Yes it could.
Skin is the biggest organ in our bodies – especially when you consider it includes our guts. The gut is not in the body. Like skin, the mucosa of our guts is a boundary between what is outside us and truly inside us.
Serotonin was discovered in the gut. Almost all antidepressants derive from anti-histamines, with as many effects on histamine as on serotonin and as everyone knows histamine and skin (as well as gut mucosa) are closely linked.
One of the strangest things is that today we seem to know more about the brain than about skin which faces us every minute of the day and which can do dramatic things in terms of sensing weather and other environmental changes. Skin contains proteins that can ‘see’ , ‘smell’ and sense in lots of ways we are only beginning to understand.
And of course the gut microbiome has become a hot topic lately.
In terms of investigating PSSD, skin offers what looks like a manageable challenge – explain why a very small patch of skin goes numb and why it stays numb. This should be easier than probing the brain. Should be – except we ignore skin.
These posts looked beyond PSSD to withdrawal, making the point that if we understand PSSD, we are likely to understand a great deal, if not everything about antidepressant withdrawal.
More recently our focus on Small Fibre Neuropathy (SFN) has slipped, as have engaged with proteins and transcription factors like prokineticin, kisspeptin, p 53 and p 63. These may all fit together as one story, especially when it comes to thinking about a cure.
So it was exciting to have a Finnish PSSD group get in touch last week and let us know that they are a group of 36 people with PSSD, growing rapidly, linked to a larger 1700 person antidepressant withdrawal group. The group is supported by a number of Finnish neurologists.
Small Fibre Neuropathy (SFN)
Of these 36, all who have been tested so far have positive SFN biopsy results. Many in the withdrawal group also have positive biopsy results.
What does a positive biopsy result look like? SFN biopsies are usually taken on the leg. The instrument used a PGP9.5 has a normal range of greater than 1 per mm intra-epidermal nerve fibre density (IENF).
One of the volunteers in Finland was measured at 2.5 IENF/mm. But for a 30-year-old male this result is extremely low and points to small fiber neuropathy. The average for a 30 year old male is 10.6/mm and should always be more than 8/mm. Many in the group have densities ranging from 0.8 to 4.
Normal ranges may vary with instruments used but in all cases age must be taken into account.
Anyone with any form of protracted withdrawal, especially involving dysautonomia, should consider getting these tests done. You will likely at the moment find neurologists slow to take this step – wanting to do other tests first.
You should also get your eyes reviewed, perhaps with corneal confocal microscopy – see RxISK vision. And you should have cardiac tests, an ECG Holter monitor, to look for heart rate variation and QT interval problems – Tell Tale Heart and Reverse Dodo.
Causes of Small-Fibre Neuropathy
Confirming a drop in the number of nerve-endings gives us an initial diagnosis but after that there is the question of what has caused this drop. Diabetes can cause SFN. Auto-immune conditions can too.
Forty years ago, there was evidence that SSRIs have effects on the immune and inflammatory systems. Many people taking them also develop auto-immune phenomena. This opens up the issue of checking for auto-antibodies in PSSD and related conditions.
Some patients with PSSD have recently reported auto-antibodies to FGFR3. There are likely other tests that would come up positive and these need to be explored, as they open up a possibility for treatment.
Drugs have long been know to be a cause of SFN but most articles on the condition do not mention this – other than mentioning the link to cancer chemotherapy. Thalidomide however famously caused a peripheral neuropathy. Isotretinoin does too. And so do SSRIs and alcohol and some vitamin deficiencies. These are unlikely to be auto-immune states.
The loss of nerve fibres also on its own likely doesn’t cause the problem – so much as the loss of sensory receptors linked to those nerve fibres. In the case of antidepressants we are likely looking at a Sensory Neuropathy that can affect vision and touch.
What about balance and dysautonomia? Balance critically depends on what are called proprioreceptors in our joints. Damage those and we cannot sense where our limbs are or body is. This might well play a part in the first enduring post drug problem that was recognised – tardive dyskinesia.
In the same way, dysautonomia likely hinges on malfunctioning sensory receptors within the body.
Systems like the autonomic systems are deep inside our bodies and we are unlikely to think they are sensory problems. We think of our eyes and ears as focussed on what is happening around us but 90% of the sensations we first pay heed to arise within us. Just think of what happens when your bladder or bowel are full or irritable and you will realise these can often command attention ahead of apparently more important things around us. Disturbances in these areas, our muscles and heart, rather than anythng wrong in the brain, likely give rise to the phenomenon of Brain Fog.
Covid has thrown a complicating factor into the mix. There is some evidence that SSRIs may have anti-Covid effects perhaps through actions on p 63 transcription factors leading to changes in ACE2 receptors – see Holy Grail.
Covid, and its mRNA vaccines, appear capable of inducing sexual syndromes that overlap with PSSD, PFS and PRSD. Welcome to Mondor.
Covid also induces a long Covid-syndrome that overlaps the protracted withdrawal syndromes from antidepressants.
The Covid vaccines also trigger auto-immune reactions, generate auto-antibodies, and either through these or other means lead to Small Fibre Neuropathies.
This is a complicating factor for anyone with PSSD or antidepressant withdrawal, as almost everyone now has had a vaccine. Do my SFN biopsy results stem from my antidepressant or from a vaccine? The person best place to decide this based on the timing of when problems emerged is you.
It is just as much a problem for people trying to manage a vaccine induced SFN. Many people who have had problems on the vaccines, with injuries afterwards, have been put on SSRIs and some of their difficulties may have come from this source.
Just because SSRIs may be helpful preventing Covid doesn’t mean they are a treatment for Long-Covid etc. PSSD is a lot worse than Long-Covid. Until we are absolutely sure they cannot independently cause problems, SSRIs are best avoided by anyone with Covid or vaccine induced problems.
Covid, and its vaccines and SSRIs all have effects on ACE2 receptors, so when you have a test result showing ACE2 receptor antibodies, will anyone know for sure what this means?
The Vaccine injured are natural allies for those with PSSD and SSRI withdrawal.
REACT19.org is a fabulous site created by Bri Dressen and colleagues to collate all information from those who have suffered vaccine damage.
The site is a treasure trove of information about biopsies, antibody tests and possible treatments that have proven helpful.
One of the concerns about SFN in the PSSD community is that this seems to point to irreversible damage. This isn’t the case. It is clear that some people with PSSD recover fully, and many have windows. The damage therefore is reversible.
We also know that small fibres can regenerate; our problem therefore is to work out what is stopping this from happening.
This is where research on P63, prokineticin, kisspeptin and other compounds remains important.
If the problem in some cases arises from auto-antibodies, this might open up the possibility of IVIG (intra-venous immunoglobulin) treatments. REACT19 is a fount of knowledge on treatments like this. It is not curative – but can provide windows of recovery
More recently there has been great excitement about a use of CAR-T therapies for auto-immune disorders. These began life as a treatment for cancer but seem now to be tried in other conditions. When CAR T works, it comes closer to being a cure but the current price tag is around $400,000 USD. It might be cheaper in something like PSSD but is still likely to be a barrier.
These new therapies need exploring by the PSSD, withdrawal and vaccine injured communities.
We need people with PFS, PRSD and PGAD to get SFN tests done to see if they too have biopsy evidence of changes.
Everyone with visual changes after antidepressants should get Corneal Confocal Microscopy (CCM) tests done.
We need people with tardive dyskinesia after antipsychotics to get SFN tests done to see if they too have biopsy evidence of changes.
We need the antidepressant withdrawal community to recognize that PSSD, PFS, PRSD and PGAD are withdrawal syndromes and that the changes happening in them likely overlap with other withdrawal syndromes and point to possible causes and treatments.
We need antidepressant communities to recognize links to vaccine injuries and common actions of Covid treatments and antidepressants on factors like p 63 and ACE2 receptors.
We need to establish in the case of people with PSSD what is inhibiting the regeneration of small fibre nerve endings and work out how to intervene to allow these nerve terminals to regrow.
The factors that inhibit regrowth may be different in the case of antidepressants, vaccines, finasteride and isotretinoin.
Finding out what is preventing recovery is most likely to happen where there is liaison between the enduring sexual dysfunction groups, the withdrawal community, and the vaccine injured.
Breaking news on Vaccinations and Sexual function
RxISK acknowledges that the experiences of those who have been harmed by medical treatments are the cornerstone on which it is built, and believes this should be the case for all of medicine.
See Black Robe, White Coat for more detail on this people acknowledgement