The picture here shows the before and after feet of a person who has erythromelalgia. After exercise or in response to other triggers, sometimes just lying in bed, the feet or other body parts can become hot and burning, possibly painfully so. The condition is linked to sodium channels. Those who get it may have a genetic variation predisposing them to it. Those who get it have often had an antidepressant.
In 2015, we launched a complex withdrawal section aimed at exploring the idea that the collection of legacy effects that people often report after coming off SSRIs or SNRIs, look very similar to peripheral neuropathy – a condition in which the peripheral nerves that supply various aspects of our sense of touch stop working properly, resulting in sensory impairment and other problems.
From the start we have made close links between conditions like PSSD (post-SSRI sexual dysfunction) and complex withdrawal states. Understand one and you may well have the answer to the other. PSSD looks a best bet to research as the way in to all these problems because it is so clearly defined and its symptoms are right there on the surface of the body.
The most obvious examples of a sensory impairment from antidepressants is the genital anesthesia experienced in PSSD, or just the opposite, the sense of painful arousal that goes with PGAD.
Both PSSD and PGAD sufferers report a loss of libido, which for PSSD patients in particular is often viewed as indicating something wrong with the brain. But it makes just as much sense to view things the other way around. If the sensory input from the genitals is disturbed, this can be expected to lead to a decrease in libido.
This is even more the case when you find out that the fibers that seem most likely to be affected are C-fibers, and among the C-fiber group are a group of fibers that specifically transmit affective touch.
Many people on, or suffering withdrawal from, antidepressants report areas of skin numbness or altered sensation. These can be on the chest, back, abdomen – or sometimes the whole body. They often affect nipples, and are particularly common in feet and hands.
Sometimes people report the drug has altered the perceived pleasantness of touch sensations, such as a massage that now feels uncomfortable rather than enjoyable, or areas of the body that used to elicit a strong sexual response now feeling non-sexual or even causing a feeling of discomfort and irritation when touched.
In the complex withdrawal section we lay out the different types of nerve fibers that convey different aspects of our sense of touch. For example, some nerve fibers respond to vibrations and temperatures, while others respond to pressure. There are even specific fibers that produce a pleasant feeling when gently caressed at a certain speed – these are a specific type of C-fiber called C-tactile afferents. If something goes wrong with these fibers or the signals they process, this will give rise to unusual sensations or a change in the way we feel about being touched.
Sensory changes can have a much wider impact on our emotions and our well-being than people would ordinarily assume. For example, sense of smell is closely linked to parts of the brain involved in processing memory and emotions. Impairment of sense of smell can have a profound effect on the way we feel. Some people suffering from anosmia (loss of sense of smell) have reported feelings of isolation and emotional blunting. Smell is extremely important in the way we relate to a romantic partner.
In addition to touch, a neuropathy affecting small nerve fibers can also affect the autonomic nervous system which controls various automatic processes within the body such as heart rate, digestion, and breathing. This is called dysautonomia.
A condition that has increasingly come onto our radar when thinking about withdrawal and PSSD is small fiber neuropathy.
The peripheral nerves contain large fibers Alpha and Beta, as well as small fibers such as A-delta and C-fibers. In some patients, an underlying cause such as diabetes, vitamin B deficiency, autoimmune diseases, genetic mutations, excessive alcohol intake or recreational drug use can affect the large fibers, and the same factors can sometimes affect small fibers. In others, the underlying cause can be less clear but a large variety of drugs are known to cause these problems.
In 2016, a podcast about small fiber neuropathy by Anne Louise Oaklander, Associate Professor of Neurology and director of the Massachusetts General Hospital Nerve Unit – transcript Here – laid out some of the issues.
Dr Oaklander commented that if you ask doctors to list the most common symptoms of small fiber neuropathy, they usually talk about skin numbness, tingling, or pain – often starting in the feet. However, Dr Oaklander found that when patients with the condition were asked about their symptoms, they painted a very different picture. Most of them certainly did describe altered skin sensations, but they also listed the most severe and troublesome symptoms as fatigue, tiredness, reduced endurance and strength, cognitive and memory issues, dizziness, headaches, gastrointestinal problems, bloating after meals, weight loss, diarrhea, constipation, changes in sweating patterns, and difficulty urinating.
This not only reinforces the idea that problems involving peripheral nerves can affect much more than skin sensation, but it once again describes a clinical presentation that is curiously close to the one seen in people suffering from antidepressant legacy effects, or what is sometimes called protracted withdrawal.
So, we’re asking the question – do antidepressants cause small fiber neuropathy, and is this involved in PSSD, PGAD and protracted withdrawal?
Until recently diagnosing small fiber neuropathies has not been straightforward and for this reason these conditions have remained relatively unexplored. There are currently two main tests available, but first, it’s worth explaining what type of test isn’t suitable.
When patients visit their doctor mentioning disturbances of sensation such as numbness or pain, which for over a century a doctor will link to peripheral neuropathy, they are often sent for a nerve conduction study. This involves passing electrical pulses through the arms and legs and measuring the result with a machine to assess how well the nerves are working. The problem is that these tests only investigate large nerve fibers. Patients with small fiber neuropathy typically have normal results on nerve conduction studies. The risk is you will end up being told there is nothing wrong with you – it’s all in your mind.
The first type of test specifically used to assess small fiber neuropathy is quantitative sensory testing (QST). Devices which produce small vibrations and hot and cold temperatures are placed against the patient’s hand and foot, and they are asked if they can feel the sensation. The results are used to produce a graph which indicates any abnormalities in the patient’s thermal and vibratory thresholds. While this can be a useful test for detecting the presence of impaired sensation, it doesn’t specifically show that the problem is peripheral. In other words, it shows that the patient’s skin is numb, but the source of that numbness could be in the skin, the spine, the brain, or anywhere in between. Nevertheless, it’s noninvasive and can usefully show that there is indeed a problem that can be measured.
The second type of test is a skin biopsy with assessment of intra-epidermal nerve fibre density (IENFD). These tests go back a little over a decade now and have begun to come into use in many clinical settings.
A small amount of skin is extracted, generally around 3mm in diameter, one-tenth of an inch, usually from the lower leg. It is typically done under local anesthetic. The removed skin is then analysed to check for nerve fiber density.
Does this mean I have to have a skin biopsy of my penis or labia? No. In the case of both PSSD and PGAD, along with withdrawal, and also PRSD and PFS, our hunch is the damage is pretty extensive. The genital disturbance might be by far the most obvious thing but there will be in almost all cases a disturbance of sensory input to other areas too.
In the case of erythromelalgia of the feet for instance, the biopsy is taken above the ankle. With PSSD, especially if the disturbance sensations extend to inner thigh or groin as they often do, you could test there but in fact with both withdrawal and PSSD there is a good chance you could test almost anywhere.
While QST and skin biopsy are considered the standard methods for investigating small fiber neuropathy, the very latest kid on the block is another test called corneal confocal microscopy. This involves taking a scan of the patient’s eye. Its supporters claim it is more accurate than either QST or a skin biopsy. At the moment, we are not certain just what is involved or whether it is available outside of a research setting.
The paper that brought this to our attention featured the cases of two teenagers with disturbances of their feet and legs, like the erythromelalgia above. In this case the disturbances of their sensory nerves could be picked up in their eyes.
In all these cases of PSSD and withdrawal, there are likely to be fairly extensive disturbances throughout the body and these peripheral changes in many cases will explain the seemingly central changes like disturbed sleep, memory problems and loss of libido.
We need anyone reading this to help us all find out where these tests can be done (ie. which hospitals or clinics) and how much they cost. You might find the tests listed under the neurology department of some hospital websites. Or you could try writing to the neurology department at your local hospital to ask if they carry out these tests, and if not, where your nearest hospital would be.
We also need PSSD and complex withdrawal sufferers to actually have QST or a skin biopsy, or ideally both, and let us know the results. If anyone manages to arrange these tests, please let us know how you did it, how it went, what it cost and what the results were.
We may be able to generate referral letters, either to a family doctor or a specialist, especially for anyone who has submitted a RxISK report on PSSD, PRSD, PFS or enduring withdrawal.
Having even a few people produce findings of abnormalities would put us in an immeasurably stronger position to raise awareness of PSSD and understand the physiology behind it.
It would also totally transform the debate about withdrawal.