In a society where physicians call for antidepressants to be made available over the counter, and where social media algorithms boost glamorization of so-called “hot girl pills,” it is safe to say that antidepressants have escaped the wheelhouse of physicians and psychopharmacologists and are embedded in the zeitgeist of America.
Antidepressants are America’s first-line treatment for the most common mental health problems, e.g., depression, anxiety, and insomnia. American clinical practice guidelines for psychiatrists, primary care and VA doctors, and even psychologists recommend antidepressants either as monotherapy or in combination with psychotherapy for initial treatment of mild to moderate depression (European guidelines differ, with the UK’s NICE and the World Health Organization explicitly recommending against the use of antidepressants for mild to moderate depression). When the Covid-19 pandemic brought its cascade of anxiety, trauma, and grief, many Americans turned to antidepressants for relief.
This highlights the ubiquity of antidepressants in America—tens of millions in the US consume them every day. Thus, it is crucial for the public to appropriately discern their efficacy and side effects.
Recent studies and critiques are challenging the antidepressant status quo. The chemical imbalance theory of depression, still widely believed among the general populace, was resoundingly debunked in 2022 with Joanna Moncrieff and colleagues’ umbrella review. Moncrieff and her co-authors succinctly summarized the public health implications for antidepressant prescriptions in a follow-up BMJ comment: “The public should be aware that we don’t know what antidepressants do to the brain or how they work to allow more informed choices about their treatment.”
Establishment psychiatry proclaims the real-world effectiveness of antidepressants largely due to results from the NIMH-funded STAR*D, with its dazzling claim of “nearly 70%” remission rates when depression is treated with antidepressants. Yet rigorous studies have illuminated a slew of deceptive research practices behind the study’s glamorous results.
Following a number of peer-reviewed critiques of STAR*D published in the preceding 15 years, H. Edmund Pigott and colleagues published an omnibus 2023 re-analysis of STAR*D patient-level data, attempting to correct the scientific record. They found that the true remission rate was 35%, half the rate of the advertised 67%. One method used by the STAR*D researchers to manipulate the data was that a large portion of the initial recruitment sample did not meet criteria for depression but were ultimately included as having “remitted” after drug treatment—because they still didn’t meet the criteria for depression at the endpoint. And at the end of the 12-month follow-up, just 3% of the sample stayed well—the rest either did not remit, remitted and relapsed, or dropped out of the study.
Pigott and colleagues itemized a deluge of research misconduct in STAR*D, compelling a pair of psychiatrists to call for its retraction. Furthermore, it seriously calls into question whether standard practice for antidepressant prescribing is evidence-based medicine.
Similarly, landmark research spearheaded over decades by Harvard psychologist and placebo researcher Irving Kirsch exposed that antidepressants are clinically useless. Recognizing that publication bias massively inflates antidepressant trial results, Kirsch has found that the drugs are essentially equivalent to a placebo—and the slight statistical benefit shown in some analyses are likely due to breaking the blind in the individual studies. “Analyses of the published and the unpublished clinical trial data,” Kirsch writes, “are consistent in showing that most (if not all) of the benefits of antidepressants in the treatment of depression and anxiety are due to the placebo response, and the difference in improvement between drug and placebo is not clinically meaningful and may be due to breaking blind by both patients and clinicians.”
“Taking antidepressants for depression,” a trio of authors assert in a narrative review of Kirsch’s work, “may be equivalent to taking a tic-tac, albeit a very expensive one that also causes sexual dysfunction and dry mouth.”
Though antidepressants provide no clinical benefit beyond placebo, they have been shown to provoke a devastating side effect at a greater rate than placebo—suicidal behavior. Given that major depression is the mental illness most commonly associated with suicide, antidepressants should at the very least lessen its risk. That is not so.
The advent of SSRIs in the 1980s and 1990s came with the typical psychiatric sales pitch that these medications protect against adverse outcomes of depression, particularly suicidal behavior, and that they are “life-saving.” However, researchers have found that drug companies conceal negative results and adverse outcomes in published articles. Independent researchers, though, have shown that the drugs are linked to consistently increased risk of suicide, particularly in youth. These data led the FDA to slap a black box label on antidepressant drugs, warning of this risk up to age 25.
The aggregate of these analyses—exhaustive, data-driven, systematic research—topples the conceptual house of cards in which the antidepressant hegemony resides. They are said to cure chemical imbalances, but no such serotonin imbalance has been found; they are prescribed to treat major depression, but are also liable to provoke suicidality, the most dangerous symptom of depressive disorders, and have clinical effects indistinguishable from a placebo; they may provide a temporary reprieve from debilitating sadness, but by blunting one’s passion, emotion, and drive, potentially inducing prolonged sexual dysfunction.
I fear that the American populace has been coerced—by pervasive pharmaceutical marketing and academic psychiatry’s obfuscations—into believing a compelling but dubious tale about the nature of antidepressants. We Americans have come to view them as sophisticated brain chemistry enhancers that target and eliminate depression as if it were a virus; and that they cause only marginal side effects and we can easily stop using them whenever we want. That is the dominant narrative.
The aforementioned research shows us that this is a harmful and erroneous interpretation of how antidepressants affect us. It would behoove us to challenge and reframe this narrative.
For example, the biomedical model defining depression as a dysfunction of one’s neurochemistry is reductionist, constraining, and myopic. Its theoretical and empirical foundations are tenuous and it subordinates the social, historical, and psychological dimensions of depression. It, and mental distress generally, is better understood at the level of human psychological experience—the aggregate of the emotions, thought processes, and motivations that one contends with daily and the contextual factors that influence them.
Clinical psychologist Jonathan Shedler invokes pixels and movies as a metaphor to illustrate why examining only neurons and neurotransmitters are insufficient for helping us understand one’s “mental life” and treat emotional suffering:
“When you watch a movie, you are seeing arrangements of pixels. The movie is 100% dependent on pixels and cannot exist apart from them. But knowledge of pixels is irrelevant to understanding the movie. We can know everything about pixels and have no concept of Luke Skywalker, Darth Vader, or the battle with the empire.”
Furthermore, largely due to inadequate informed consent in psychiatric drug prescribing, antidepressants are often branded “safe and effective,” but this label extinguishes the considerable nuance inherent in long-term consumption of psychoactive medications.
When accounting for the long-term patterns of antidepressant use, whereby antidepressants are used for years and sometimes decades, safe and effective inverts to perilous and iatrogenic. Notably, the evidence base of antidepressant clinical trial data submitted for FDA approval tells us virtually nothing about long-term outcomes. A recent preprint found that 88.5% of these trials lasted 12 weeks or less, signifying a significant blind spot for an enterprise, psychiatry, that purports to derive guidelines from “gold standard” evidence.
Research investigating long-term outcomes of antidepressant treatment, which better represent real-world trends than randomized trials, has shown worsening outcomes. A study published in 2018 tracked depression symptoms in a community sample of 591 adults in Zurich. Over the course of 30 years, results showed that antidepressant use predicted worsening depression. Another longitudinal survey published in 2017 found similar results in US adults. At a 9-year follow-up, respondents using antidepressants reported worse symptoms compared to those receiving non-pharmacological treatments or no treatment. Both of these studies controlled for a variety of factors, including baseline depression severity, so this is clearly not a case of backwards confounding.
The phenomenon of worsening and unremitting depression after long-term exposure to SSRIs has been labeled tardive dysphoria. Though still ignored by the psychiatric establishment, it comports with tardive dyskinesia, the neurological side effect of antipsychotic medication. Both tardive dysphoria and tardive dyskinesia are theorized to occur due a mechanism of “oppositional tolerance,” wherein the brain adapts to altered neurotransmitter activity caused by antidepressants. In other words, SSRIs and other psychiatric medication may cause the chemical imbalance they are alleged to fix.
Antidepressant physical dependency, though categorically different from addiction caused by chronic use of drugs like heroin and cocaine, can produce withdrawal symptoms nearly as debilitating as the aforementioned street drugs. Intolerable withdrawal symptoms such as brain zaps and akathisia challenges the long-held claim of the American Psychiatric Association that antidepressant discontinuation is a relatively straightforward process occurring over several weeks. The most comprehensive text on psychiatric deprescribing, The Maudsley Deprescribing Guidelines, proposes gradual discontinuation, contending that successful antidepressant tapering occurs over “months more often than weeks, and sometimes longer, for longer‐term users.” The Maudsley guidelines advocate for flexible and adjustable antidepressant discontinuation, acknowledging that the process could span years.
Psychiatrist Mark Horowitz, a co-author of the guidelines, regularly comments on his own story of stopping antidepressants, describing it as a harrowing ordeal of trials and tribulations, catalyzed by an onslaught of withdrawal symptoms. While not applicable to all who receive antidepressant prescriptions, personal histories by Horowitz and other survivors of iatrogenic psychiatry—for example, Brooke Siem’s May Cause Side Effects and Laura Delano’s Unshrunk—may provide more informative and holistic accounts of antidepressant harms and injuries, which are tremendously under-spoken in current mainstream psychiatry.
I argue that we should consider antidepressants more akin to alcohol than antibiotics. Their effects better resemble recreational drugs than medications.
Thankfully, Joanna Moncrieff has long proposed a framework for re-evaluating how we understand antidepressants and psychiatric medications in general. Moncrieff juxtaposes the disease-centered model of psychoactive drug effects, the mainstream position in the American mental health industry, against the more pragmatic drug-centered model. While the disease-centered model holds that psychotropic drugs treat an underlying abnormal disease process (à la insulin for diabetes), in the drug-centered model, psychotropic drugs alter one’s whole brain state, consequently influencing thoughts, emotions, and behaviors for better or worse (à la alcohol for social anxiety).
The problem with the disease-centered model, as we have already examined, is that there are no resolute biomedical models of mental illness, and therefore psychotropic drugs are influencing the nervous system globally, and not an underlying disease process. The drug-centered model, however, recognizes that psychoactive drugs, whether they be recreational drugs or psychotropic medication, are mind-altering, capable of stimulating a range of feelings such as euphoria, relaxation, arousal, and agitation. Psychoactive drugs alter the mind and therefore alter the manifestation of mental health symptoms, temporarily lessening psychological pain. Many find the acute effects of altering one’s mind useful in the short term, for example the after-work beer or glass of wine to manage stress. However, over the long-term, the harms of neurotoxicity, drug dependence, and undesirable mental alterations, all of which are probable for psychiatric drugs as they are for recreational drugs, dramatically outweigh the benefits.
Considering the drug-centered model of psychiatric medications, imagine someone were prescribed alcohol daily for years to treat mental illness. Even at relatively low doses, for example one beer or one ounce of liquor a day, most would balk at such a recommendation and impugn their prescriber for malpractice. Because recreational psychoactive substances have such dramatic effects on our mental states, and because there is overwhelming common knowledge about the negative consequences of chronic use of them, we immediately render this notion foolish—the burden of altering our psyches on a long-term basis is unsustainable.
Yet, we don’t ascribe this same scrutiny to antidepressants despite the reality that they are mind-altering drugs. Antidepressants may not produce immediately noticeable inebriation like alcohol and stimulants, but they are nevertheless psychoactive and mind-altering. The risk-to-benefit assessment of antidepressants, when examined through the lens of the drug-centered model, may ultimately compel millions of Americans to rebuff these medications and choose alternative methods for coping with distress.
As Moncrieff and colleagues write, in a 2013 article discussing the psychoactive effects of psychiatric medication: “Only when we appreciate the nature of psychiatric drugs as psychoactive substances can we start to accumulate the knowledge necessary to enable prescribers and consumers to use these drugs safely and effectively.”
America has an unhealthy relationship with antidepressants because we, collectively, fundamentally misunderstand them (we can thank big pharma, academic psychiatry, and the mainstream media for that). The very name “antidepressant” is misleading given that they were not originally formulated to attack depression neuropathology (it doesn’t exist). I propose that we rename them serotonin activity destabilizers, because they are indeed SAD!
