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Key points
- SSRIs are known to have thousands of actions on the brain and body, some not well-studied or understood.
- Adverse effects can continue long after the drugs are stopped, raising questions about their toxicity.
- A new perspective on dysregulation challenges the role of serotonin and puts the focus on the body and organs.
In a recent webinar, “Why Are Antidepressants So Difficult to Stop?,” the distinguished pharmacologist and psychiatrist David Healy raised troubling, little-known details about the history of selective serotonin reuptake inhibitors (SSRIs) and the several thousand actions they have been recorded as having on the brain and body. I had a number of questions.
Chris Lane: What are some of the least-known actions from SSRIs that have been reported, and why can these persist in some people months, even years, after they are stopped?
David Healy: Anhedonia and problems tied to vision, balance, sexual desire, and one’s gut and bladder happen regularly on SSRIs and can endure decades after stopping. Pharmacology has no answer for why. Over many years, I have seen active efforts to avoid telling people about these hazards, so as not to deter them from getting treatment.
CL: One of your key claims is that “SSRIs are anxiolytic rather than antidepressant.” They act principally on sensory systems in our guts and blood, where most serotonin is produced and stored, and involve the brain much less than has been taught. Have we been approaching withdrawal problems from SSRIs from the assumption that they involve a deficiency of neurotransmitters rather than as a broader dysregulation of the body?
DH: SSRIs were discovered because of their anxiolytic effect. A branding as antidepressants later became a marketing maneuver. They don’t work for significant depressive disorders such as melancholia. The serenic effect they can produce can help some mild depressions, but has come with adverse effects and behavioral rebranding—we are no longer seen as nervous, stressed, tense, or anxious, but as depressed. That relocates what may be social problems in us. Withdrawal problems from SSRIs are dominated by the same thinking.
CL: How does focusing on dysregulation alter or resolve that issue, and would a different treatment picture emerge that could pinpoint causes more accurately?
DH: Dysregulation makes it clear we don’t know what is going on. Pretty much everyone given an SSRI was put on an unnecessarily high dose (20 mg of fluoxetine) from the outset. We need to get bodily systems back into something closer to normal shape, which might mean turning to strategies like routine exercise to force our bodies to re-regulate.
Importantly, drug dysregulations do not stem from our mental state. If we turn to therapy for the dysregulation, it will likely misidentify the source of the harm—as trauma rather than drug-induced toxicity. There is a growing lifestyle and coaching industry whose skill lies in locating problems in us rather than in being able to eliminate them. People with no idea neurochemically what is going on with SSRIs should not be collecting fees from those made vulnerable by the damage.
CL: In the webinar, you argue that a “brain bias” in psychiatry—coupled with the deceptive marketing of SSRIs as adjusting a “chemical imbalance”—helped lay the groundwork for the “myth of low serotonin” as a leading cause of depression, with SSRIs cast as its closest neurobiological solution. In your words, “The Serotonin of Psychiatry is as unreal as the Tooth Fairy. It can’t be measured.” Should 5-HT1A (serotonin) receptors be de-coupled entirely from SSRI withdrawal problems, or are you saying overemphasis of serotonin as a cause of depression has also disposed us to overestimate the benefits of SSRIs?
DH: Serotonin has nothing to do with depression, but its marketing has captured the health food industry and clinical psychology. Linking withdrawal to tapering at serotonin receptors similarly opens a door to herbalists and neuroplasticioners—those who tell us that their help in manipulating our neuroplasticity will solve the problems of drug toxicity.
The difficulty with all this is that we know that many of the effects of these drugs stem from actions on regulatory proteins like p63 and enzymes such as carbonic anhydrase—actions that need thorough investigating, as distinct from buzzwords that may seduce a client.
CL: Your work documents a history of thinking about withdrawal as “relapse,” “discontinuation,” and “symptoms on stopping” (SOS)—emphases that tend to favor drug-makers via continuation at higher dosage or on a different SSRI. How does emphasizing dysregulation impact emphasis on antidepressant withdrawal (AW) and, perhaps especially, protracted withdrawal (PWS)?
DH: We are dealing with toxic states. Talking about protracted withdrawal makes it sound like an opioid problem located in failed people rather than a crazy marketing program that overrode common sense. We need to recognize and address this first. We also need to reverse what has become a type of “bio-babble” in our culture and discourse—it’s not just oversimplifying and incorrect, but infantilizing.
CL: Is there a risk that AW would lose urgency or precision as a medical and drug-related state? Could the adjusted emphasis lead to even greater confusion over the causes of the dysregulation?
DH: We already have people lining up for medical assistance in dying—euthanasia. Could things be much worse? Treatment-resistant depression came into existence with the SSRIs. The only remedy is to start calling these states antidepressant-induced toxicity.
CL: Stopping SSRIs abruptly, “cold turkey,” is widely discouraged—as with benzodiazepines, antipsychotics, gabapentinoids, and many other types of drugs—as risking exacerbating the onset of withdrawal. In the webinar, you favor caution and a slow taper. What’s your argument with hyperbolic tapering?
DH: Tapering has been around for decades. It made obvious sense to sufferers when they were being ambushed by seriously troubling states after missing a dose. But the word “hyperbolic” is a Johnny-come-lately, and essentially meaningless. Worse, conveying that we know precisely how to get people off SSRIs allows pharma to gaslight patients, to claim there is no problem a little tapering can’t solve.
CL: Since the 1960s, you show, researchers have known that “within 30 minutes of taking a first SRI at one-tenth of a standard antidepressant dose, people [can] get genitally numb.” In addition, that it was healthy (i.e., non-depressed) volunteers in the first trials suffering widespread and lasting sexual dysfunction that led to manufacturer knowledge of the problem. How as a result did post-SSRI sexual dysfunction (PSSD) fly under the radar so many years, and what do you advise those experiencing the condition when remedies are scarce, often untested and unproven, and trained consultants difficult to find?
DH: PSSD flew under the radar for two reasons. One was that, from 1991, with the suicide crisis linked to fluoxetine (Prozac), regulators and the media tacitly agreed we should not warn about the problems SSRIs and SNRIs cause, for fear of deterring people from getting the benefits.
Second, PSSD in particular was something no one wanted anyone to know they had, so almost all sufferers remained anonymous and, for that reason, the condition has remained in the shadows. Academic journals had no articles, and most media can’t talk about problems without being able to put diagnosable people on camera.
At present, neither the companies that make SSRIs nor academic researchers are looking at this condition, which, if we include those unable to get off the drugs, likely affects millions. All of the research for these and other drug hazards is increasingly done by those affected. People with no background in healthcare or science are coming up with breakthroughs, but that’s a bizarre way to do things, pointing to a badly broken system.
References
Healy, D. (9.7.2024). Why Are Antidepressants So Difficult to Stop? A New Understanding of Drug Dysregulation Syndrome and How to Manage it. Webinar hosted by Mad in America, published at RxISK.org.
