9. Serotonin receptors and protracted antidepressant withdrawal

Do they always matter?

Introduction

So for five years I had protracted withdrawal sensations from psychiatric drugs. I was very scared that these drugs had damaged me forever. I constantly wondered: will my brain and body recover, will my nervous re-find its balance after getting profoundly disturbed by all these drugs I took? Or can my nervous system find another way to reach a new homeostasis?

So that’s the topic of this video. Please note I’m not a licensed medical professional or researcher, but exploring these questions yields unexpected results that run contrary to what is sometimes presented to the public.

The Serotonin/Neurotransmitter Hypothesis of Protracted Withdrawal Syndrome

There are theories out there propagated by psychiatrists and others that the probable cause of “protracted withdrawal syndrome” is related to the serotonin system or some other imbalance of neurotransmitters. Sound familiar? Psychiatrists are obsessed with talking about these specific chemicals as the source of human distress even for our post-psychiatry suffering. Here’s a snippet from a Mad in America podcast with such a psychiatrist: 

“Now, when you stop the antidepressants, your serotonin levels go back to normal. But your brain doesn’t just snap back into how it was before the drug was there. Those adaptations, those changes, take a while to get back to normal. In fact, in one study, after stopping antidepressants in patients, there were changes in the serotonin system for up to four years after stopping. In animal studies, findings are similar: after stopping antidepressants, there are changes to the hormonal system that we think can last for months or years . . . That is probably why withdrawal syndromes can last for so long, because of the residual effects on the brain after stopping the drugs.” 

He goes on to say they don’t really know but this is what they think. And I think it’s very probable that this explains acute withdrawal, that the brain must readapt itself to life after the drugs. But if someone is struggling, as I was, with protracted sensations going on for a long time, maybe years, is this still always a viable explanation? Here’s a quote from The Maudsley Deprescribing Guidelines:

Protracted withdrawal symptoms are thought to be caused by changes to the brain during exposure (generally long-term) to antidepressants, which persist for months and years after stopping the drugs. Indeed, there is PET imaging which demonstrates changes to serotonergic receptor sensitivity for months and years after the medication is stopped (P. 96).

Now these quotations I’ve given from both the podcast and the deprescribing guidelines give the same academic reference as evidence for this idea that the serotonin system or related hormones are probably responsible for protracted withdrawal sensations. But if we look at this reference, a brain imaging study, it reveals that these psychiatrists are kind of making misleading statements that fail to provide essential context. 

So here’s the actual study: Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635.

In this study the participants were divided into two groups, one who had never taken “antidepressants” before and another group who had taken them but had stopped them six months to several years ago. And what’s found is that in the people who had previously taken “antidepressants”, there were comparably significant decreases in certain serotonin receptors. This suggests that these downregulated receptors as a result of taking drugs could take years to bounce back, if at all. And the psychiatrists that I previously quoted on that podcast, in the Describing Guidelines, that’s what they rightly pointed out. 

However they also stated this is what’s probably causing protracted withdrawal syndrome. But here’s why that’s misleading: because the participants in the study with fewer serotonin receptors, they felt fine. They weren’t in withdrawal. They weren’t “depressed.” They felt healthy. In fact a prerequisite of the study was that all the participants who entered it felt well. So how is a decrease in serotonin receptors the cause of protracted withdrawal syndrome? The way this information is presented is misleading. Not saying it’s intentional but I don’t know why it’s lacking context. These people are not in withdrawal.

Now the authors might back-pedal and say well maybe it’s not the serotonin system per se but other neurotransmitter systems because they’ve been shown to be altered in animal studies too. Yeah. But if the serotonin receptors, which are presumably the most implicated in SSRI drug withdrawal, if these receptors haven’t fully recovered and yet the people are fine then why should we assume that other chemical receptors that are less directly involved are now responsible? Especially since we’re misled to start with, it makes me wonder, what else is not being said? 

So why are they doing this? Well, again, I’m not saying the authors are intentionally misleading us but it’s pretty apparent that they’ve accepted a traditional biomedical model for protracted withdrawal probably because this is just what they were educated with, but this model has been a travesty for decades in its attempt to understand mysterious syndromes, like more recently protracted withdrawal. Let’s take a brief look at why this is and then how people are actually going around these bioreductionistic ideas to heal themselves. And that’s not to say people can’t resolve things with this model, but that it’s not necessarily giving the whole picture or solution for everyone.

The Failure of Biomedical Models

The biomedical model is the dominant model in the medical industry, including psychiatry. It’s this idea that something is always broken or diseased or off balance. Now to be fair this biomedical model has value for acute withdrawal, aspects of tapering, and specific iatrogenic injuries and other things like a broken arm or maybe an infection. But for those of us with mysterious syndromes that go on and on, they have no idea why this is and so they just start blaming things, blame structures in the body (things that don’t look right even if it’s not even related) or maybe they blame your genes. But when no explanatory cause is found this approach fails pretty miserably. 

How can we know this? As scientific research gets more advanced on medically mysterious syndromes, there are now record numbers of people with chronic pain, migraines, fibromyalgia, eczema, chronic fatigue, Long COVID with no tissue damage, and how many people are psychiatrized now with these meaningless labels. And when these professionals don’t know what’s going on they just medicalize people and give them drugs, surgeries and in some ways people are more disabled than previously. Future research on “protracted withdrawal syndrome” seems likely to yield similar results. But if the serotonin system or related systems aren’t causing protracted withdrawal, as is suggested by the research I’ve shared, we could ask why it isn’t. And what else could be going on actually causing these sensations to persist?

What Can Work

So there’s actually research and clinical trials moving away from traditional biomedical models and they’re having success for a range of mysterious syndromes. Take certain pain syndromes, for instance. Many people are told that chronic pain is the result of a structural problem with their back or a muscular imbalance or nervous system problems, but for the vast majority of people this is not the cause of the pain.

In fact two clinical trials, one on something called Pain Reprocessing Therapy, and the other on Psychophysiologic Symptom Relief Therapy, between 70% to 75% of participants who completed these studies resolved the pain or almost entirely resolved the pain.  The “usual care” group saw about 18% to 25% resolve the pain. Obviously a massive difference and absolute landmark studies. 

So why are these approaches so superior? Well there are several factors of course but one major one is that the people in “usual care” still thought something was wrong with them. And you can read tons of frightening stuff on chronic pain, all the stuff that’s changed in the body. And one might think that all these changes are the ultimate cause of the pain. But there are also a bunch of biochemical changes in the body when we cry for instance but that’s not the reason that we cry. Usually it’s because we’re having an emotional response to something. Likewise these biochemical, neurophysiological changes for pain, a lot of times they generally don’t matter or at least they’re not the root cause of the pain. Something deeper is going on.

What’s been demonstrated in these successful clinical trials is what truly causes the pain is a continual sense of danger that our minds are interpreting, an alarm signal that keeps going in the brain that feeds directly into the brain’s processing of pain. And in part this fear is driven by people believing that we’re physically damaged and whatever ever sense of danger that we’re perceiving, whether it’s physical or emotional. Emotional threats can keep this danger signal going as well. So in pain reprocessing therapy for instance people learn there is nothing fundamentally wrong with them, and change their relationship to the sensations they feel, and do some specific work in that regard, the pain is then very likely to resolve. This has also been used successfully for people with Long COVID without tissue damage, and anecdotally people have used this approach for so many different syndromes.

So when psychiatrists tell us that we have something wrong with our serotonin system or whatever without any proof, without providing context, they are potentially perpetuating the syndrome. They are setting people up to potentially get worse. It’s by learning that we’re not damaged despite how badly we might feel and addressing other things making us feel unsafe that we can begin to work toward resolving the syndrome because the long-term changes might very well be completely inconsequential. 

Another Example of Meaningless Changes

I’ll give one more example of why these changes for long-term syndromes might not matter. So pain rehabilitation physician John Sarno whose ideas were used in the clinical trials I mentioned, when he first saw people for chronic pain he would push down on certain areas of their backs that would almost always trigger pain. (For people without chronic pain, he could push down on these areas and it wouldn’t hurt them.) Then after people resolved the chronic pain after taking Sarno’s program and got back to living their lives, they’d have a follow-up with Sarno and he would push down on their back again and, guess what, they would still have pain in these key areas. But only when he pushed on them. This had no bearing on their day-to-day pain-free life. So what this means is that there can be persistent neurophysiological changes that last perhaps indefinitely but they are totally irrelevant to our everyday life. They don’t matter. Injuries heal but maybe not in the way we expect them to. Sometimes the brain can be smarter than us and find other ways of rebalancing itself in ways that this limited biomedical model can’t understand. But there is a world beyond this biobiobio one and there are new ways of understanding protracted withdrawal so if any of this resonates with you, you can find out more about the approaches I mentioned here on this Substack and I’ve made other videos on this topic as well. So feel free to check that out and I wish you all the best no matter what path you choose.