Tag: chemical imbalance theory

10/25/22

The Myth of the Serotonin Theory of Depression

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A research article by Joanna Moncrieff, Mark Horowitz and others, “The serotonin theory of depression: a systematic review of the evidence”, published in the journal Molecular Psychiatry in July of 2022, continues to draw media attention to its findings. The researchers did a systematic umbrella review of the principle relevant areas of research and concluded that the main areas of serotonin research provide no consistent evidence of an association between serotonin and depression. “We suggest it is time to acknowledge that the serotonin theory of depression in not empirically substantiated.” In other words, it’s a myth.

The response from many psychiatrists to the article was that the serotonin imbalance theory has not been treated seriously within the field for many years. Neuroscience News & Research quoted several who thought the findings were not surprising. Dr. Michael Bloomfield a consultant psychiatrist and head of the translational psychiatry research group at University College London said he didn’t think he’d met any serious scientists or psychiatrists who thought that “all causes of depression are cause by a simple chemical imbalance in serotonin.” Allan Young, the director of the Centre for Affective Disorders at King’s College London said, “Most psychiatrists adhere to the biopsychosocial model with very few people subscribing to a simple ‘chemical imbalance’ theory.”

According to Ang, Moncrieff and Horowitz in Is the chemical imbalance theory an ‘urban legend’?, historically there was a considerable promotion of the serotonin hypothesis of depression in both the psychiatric and the psychopharmacology literature. Research papers supporting it were widely cited. While some textbooks were more nuanced, others could be seen to unreservedly indorse it. The American Psychiatric Association (APA) published a patient leaflet in 2005 that said, “antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain.” See, “The Death of the Chemical Imbalance Theory?” on this website.

It is often assumed that the effects of antidepressants demonstrate that depression must be at least partially caused by a brain-based chemical abnormality, and that the apparent efficacy of SSRIs shows that serotonin is implicated. Other explanations for the effects of antidepressants have been put forward, however, including the idea that they work via an amplified placebo effect or through their ability to restrict or blunt emotions in general.

Moncrieff et al said surveys suggest that 80% of the general public now believe depression is caused by a ‘chemical imbalance.’ They said many general practitioners also subscribe to this view and popular website commonly cite the theory.

The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs.

Writing for The Conversation, Moncrieff and Horowitz said the serotonin theory of depression has been one of the most influential and extensively researched biological theories of depression. Most antidepressants now in use are presumed to work through their effects on serotonin or noradrenaline. Yet their study shows that is not supported by scientific evidence. “It also calls into question the basis for the use of antidepressants.”

It is important that people know that the idea that depression results from a “chemical imbalance” is hypothetical. And we do not understand what temporarily elevating serotonin or other biochemical changes produced by antidepressants do to the brain. We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.If you’re taking antidepressants, it’s very important you don’t stop doing so without speaking to your doctor first. But people need all this information to make informed decisions about whether or not to take these drugs.

The organization, Inner Compass Initiative, was able to get Joanna Moncrieff, Mark Horowitz and Irving Kirsch together for an online discussion in “Moving Beyond Myth: A Postmortem Analysis of Chemical Imbalances and Antidepressants Efficacy.” On its website Inner Compass Initiative said it is an organization that is “dedicated to helping people make more informed choices about taking and withdrawing from psychiatric medications.”

Irvin Kirsch has published several studies of the placebo effect and antidepressants, demonstrating that most of the efficacy with antidepressants is from the placebo effect. For more information on Irving Kirsch and his research, see, “Dirty Little Secret,” and “Antidepressant Fall From Grace, Part 2” on this website.

The Inner Compass Initiative moderator, Laura Delano, said the use of antidepressants in the West more than doubled between 2000 and 2015. One in seven Americans and one in six in England take an antidepressant. In October of 2004 the FDA issued a black box warning, indicating an increased risk of suicidal ideation and behavior in children and adolescents treated with SSRIs. However, their off-label use with children and adolescents has increased. In “Antidepressants in Children and Adolescents”, Boaden et al said: “From 2005 to 2012, the prevalence of antidepressant use has increased from 1.3% to 1.6% in the USA, from 0.7% to 1.1% in the UK.”

While the overall percentages are low, keep in mind that at least in the U.S. those increases took place after the FDA required a black box warning of an increased risk of suicidality with children and adolescents treated with SSRIs. In the UK, it represents an increase of over 36%; in the USA, by almost 19%.

“Moving Beyond Myth” begins with a description of how serotonin is measured within the body and a review of the history of the chemical imbalance theory. Joanna Moncrieff said it is not the case that there is a set normal level of serotonin against which people’s serotonin can be judged. She went on to say that the chemical imbalance theory of depression was one of a number of chemical imbalance theories of mental disorders that arose in the 1960s, “in the context of thoughts about drugs that are used to treat these disorders. So, they’re always directly related to the use of drug treatments.” Psychiatrists and researchers came to think that the drugs are working by targeting the underlying abnormality.

Initially they thought that noradrenaline might be relevant in depression. They hypothesized that depression might be due to lower levels of noradrenaline. But when the drugs that selectively target serotonin came out, “people started to think that the underlying abnormality was an abnormality of serotonin, rather than noradrenaline. And that is what the pharmaceutical industry took hold of and ran with in the 1990s when they started to market SSRIs.”

Her point is that chemical imbalance theories have always been dreamed up in the context of the use of different drugs to treat mental disorders. “They are based on the assumption that drugs are working by targeting the underlying abnormality, and that you can deduce the abnormality from the opposite of what the drugs do.” Mark Horowitz goes on to describe the findings of “The serotonin theory of depression: a systematic review of the evidence.”

An added bonus in “Moving Beyond Myth” is to hear Irving Kirsch describe his research into antidepressant efficacy and its relationship to the placebo effect. His most recent research was published in August of 2022 in the BMJ (British Medical Journal). Kirsch and the other researchers did a participant level analysis of randomized, placebo-controlled trials of acute monotherapy for the treatment of major depressive disorder submitted to the FDA between 1979 and 2016. The Conclusions section of the article said:

Patients with depression are likely to improve substantially from acute treatment of their depression with drug or placebo. Although the mean effect of antidepressants is only a small improvement over placebo, the effect of active drug seems to increase the probability that any patient will benefit substantially from treatment by about 15%. Further research is needed to identify the subset of patients who are likely to require antidepressants for substantial improvement. The potential for substantial benefit must be weighed against the risks associated with the use of antidepressants, as well as consideration of the risks associated with other treatments that have shown similar benefits. Because the benefits and risks might be categorically different (eg, reduced sadness v anorgasmia), weighting should be done at the individual level, jointly by patients and their care providers.

The belief that a chemical imbalance underlies depression and other mental disorders has begun to unravel. For some time, it has been set aside by researchers and some psychiatrists as an urban legend. The pharmaceutical industry may continue to hold on to the notion that drugs work by targeting an underlying abnormality and that you can identify the abnormality “from the opposite of what the drugs do.” But it is time the public became aware that the chemical imbalance theory of depression is just a myth.

09/20/22

The Death of the Chemical Imbalance Theory?

There was an article published recently in the journal Molecular Psychiatry that is getting a lot of attention online. The Hill,  Psychology Today, Neuroscience News and other new outlets highlighted an umbrella review by researchers that questioned the serotonin theory of depression and the value treating depression with antidepressants. In an article for The Conversation, two of those researchers wrote, “Our study shows that this view is not supported by scientific evidence. It also calls into question the basis for the use of antidepressants”; and the chemical imbalance theory of depression.

Joanna Moncrieff and Mark Horowitz wrote that the serotonin theory of depression was widely promoted by the pharmaceutical industry in the 1990s with its marketing a then new class of antidepressant medications, selective serotonin-reuptake inhibitors (SSRIs). This strategy became known as the “chemical imbalance theory of depression.” The theory was endorsed by institutions like the American Psychiatric Association. But this has changed, with psychiatrists like Ronald Pies, saying as early as 2011 that, “the chemical imbalance notion was always a kind of urban legend.”

Pies said in another more recent article for Psychiatric Times that he influenced the APA to replace a statement on its public education website that referred to “imbalances in brain chemistry,” with: “While the precise mechanism of action of psychiatric medications is not fully understood, they may beneficially modulate chemical signaling and communication within the brain, which may reduce some symptoms of psychiatric disorders.” The statement quoted by Dr. Pies is in article titled, “What is Psychiatry?”

Moncreiff and Horowitz pointed to another article on the same website, “What is Depression?”, where it said while several factors can play a role in depression—biochemistry, genetics, personality and environment. For biochemistry, it said: “Differences in certain chemicals in the brain may contribute to symptoms of depression.”

Looking at these articles, the chemical imbalance theory may have been weakened, but I don’t think it was defeated. It seems that when medications can “beneficially modulate” and when “differences in certain chemicals” may contribute to symptoms of depression, the imbalance theory is present implicitly. That is why the new study by Moncrieff et al, “The serotonin theory of depression: a systematic review of the evidence,” in Molecular Psychiatry is so important.

Despite the fact that the serotonin theory of depression has been so influential, no comprehensive review has yet synthesised the relevant evidence. We conducted an ‘umbrella’ review of the principal areas of relevant research, following the model of a similar review examining prospective biomarkers of major depressive disorder. We sought to establish whether the current evidence supports a role for serotonin in the aetiology of depression, and specifically whether depression is associated with indications of lowered serotonin concentrations or activity.

Their comprehensive review indicated there is no convincing evidence that depression is related to or caused by lower serotonin concentrations or activity. Yet surveys suggest 80% or more of the general public believe depression is caused by a ‘chemical imbalance.’ This belief shapes how people understand their moods, leading to a pessimistic view on what they can expect from treatment. “The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs.”

Moncrieff and Horowitz said in The Conversation article that it was important for people know the idea that depression as a chemical imbalance is hypothetical. Moreover, we don’t understand what temporarily elevated serotonin or other biochemical changes produced by antidepressants do to the brain. “We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.” And yet, the serotonin theory of depression has formed the basis for a significant amount of research over the past few decades.

Along with Benjamin Ang, Moncrieff and Horowitz explored the serotonin theory of depression in the scientific literature in, “Is the chemical imbalance an ‘urban legend’? They noted where the chemical imbalance theory was first proposed in the 1960s, focusing initially on the neurochemical noradrenaline instead of serotonin. “What came to be known as the ‘monoamine hypothesis’ (noradrenaline and serotonin are both classified as monoamines), was stimulated by the belief that certain prescription drugs targeted the basis of mood, particularly drugs that were named ‘antidepressants’.”

Following the introduction of the selective serotonin reuptake inhibitor (SSRI), the ‘serotonin hypothesis’ became embedded in the popular and professional consciousness. The pharmaceutical industry promoted the idea that depression was a result of an imbalance or deficiency of serotonin in the brain. SSRIs, which were just being brought to the market, were said to be the ‘magic bullets’ that could reverse this abnormality. In an advertisement for Zoloft, Pfizer said “while the cause is not known, depression may be related to an imbalance of natural chemicals between nerve cells in the brain” and that “prescription Zoloft works to correct this imbalance.”

Ang, Moncrieff and Horowitz more fully documented how the American Psychiatric Association (APA) supported the pharmaceutical company rhetoric from a patient leaflet produced in 2005, which said: “antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain.” Despite what Dr. Pies said, it seems that the APA did not have many psychiatrists who knew this was a kind of urban legend.

The marketing of SSRIs and the serotonin theory led to a dramatic global increase in their use. Prescriptions in England tripled between 1988 and 1998; and then tripled again between 1998 and 2018. Similar increases took place throughout Europe, with some Eastern European countries where use was previously low, increasing 5-6 times since 2000. In the U.S., antidepressant prescriptions quadrupled between the late 1980s and the mid-2000s.

There is evidence that increasing numbers of people are taking antidepressants on a long-term basis. Research has shown that believing depression is caused by a chemical imbalance is widespread among antidepressant users, encourages people to ask for antidepressants and discourages them from trying to stop.

In 2005, Jeffrey Lacasse and Jonathan Leo published a paper in PLOS Medicine that received a lot of attention. It was the first time the media grasped that the serotonin theory might not be supported by the evidence. Their paper provoked a response by the chair of the FDA psychopharmacology committee, who admitted evidence for a neurochemical deficiency in people with depression was elusive. He thought it could be a ‘useful metaphor,’ but one he would not use with his own patients. While an SSRI may work well with an individual, that “doesn’t prove that there is an underlying imbalance, defect or dysfunction in the person’s serotonin system.”

Responding to a report published by the Citizens Commission on Human Rights, a Church of Scientology organization, Ronald Pies called the chemical imbalance theory an urban legend that no well-informed psychiatrist had ever believed. He claimed the theory was spread by the pharmaceutical industry, and opponents of psychiatry attributed the belief to psychiatrists themselves. A few months later, he wrote an article for Psychiatric Times admitting that there were psychiatrists and other physicians who used the term ‘chemical imbalance’ when explaining psychiatric illness to a patient.

My impression is that most psychiatrists who use this expression feel uncomfortable and a little embarrassed when they do so. It’s a kind of bumper-sticker phrase that saves time, and allows the physician to write out that prescription while feeling that the patient has been “educated.” If you are thinking that this is a little lazy on the doctor’s part, you are right. But to be fair, remember that the doctor is often scrambling to see those other twenty depressed patients in her waiting room. I’m not offering this as an excuse–just an observation.

In 2019 Pies said while some prominent psychiatrists have used the term ‘chemical imbalance’ in public comments about antidepressants, and possibly in their clinical practices, “there was never a unified, concerted effort within American psychiatry to promote a chemical imbalance theory of mental illness.” A good bit of psychiatric opinion follows Pies’ lead and says the idea that depression is caused by brain chemical imbalances is an over-simplified explanation that should not be taken seriously. The attempt by leading psychiatrists to deny that the serotonin theory was ever influential seems to be a tactic to deflect criticism, and allow it to continue in some modified form.

Ang, Moncrieff and Horowitz concluded that during the period 1990-2010, there was considerable coverage of, and support for, the serotonin hypothesis of depression in the psychiatric and psychopharmacological literature. Research papers on the serotonin system were widely cited, and most strongly supported the serotonin theory. Textbooks took a more nuanced approach, but at other points were unreservedly supportive of the theory. Critics of the theory were either ignored or marginalized as antipsychiatry. Yet it seems in 1987 at least one critic, the Irish psychiatrist David Healy, astutely described the neurochemical theory of depression as an exhausted Kuhnian paradigm in “The structure of pharmacological revolutions.” He said it was perpetuated because it served the professional purpose of convincing patients that depression is a biological condition.

Healy was referring to the seminal work by Thomas Kuhn on the philosophy and history of science, The Structure of Scientific Revolutions. According to Kuhn, normal science referred to research firmly based on one or more past scientific achievements that a particular scientific community “acknowledges for a time as supplying the foundation for its further practice.” The process of normal science takes place within a paradigm—like the monoamine hypothesis—where research occurs within the context of a scientific community committed to the same rules and standards for scientific practice. “That commitment and the apparent consensus it produces are prerequisites for normal science.”

Any new interpretation of nature, whether a discovery or a theory, emerges first in the mind of one or a few individuals. It is they who first learn to see science and the world differently, and their ability to make the transition is facilitated by two circumstances that are not common to most other members of their profession. Invariably, their attention has been intensely concentrated upon the crisis-provoking problems; usually, in addition, they are men [or women] so young or so new to the crisis-ridden field that practice has committed them less deeply than most of their contemporaries to the world view and rules determined by the old paradigm. How are they able, what must they do, to convert the entire profession or the relevant professional subgroup to their way of seeing science and the world? What causes the group to abandon one tradition of normal research in favor of another?

So in “The serotonin theory of depression: a systematic review of the evidence,” by Moncreiff at al, we may be witnessing the death of the old paradigm for depression.

Kuhn went on to observe that the proponents of competing paradigms are always at least slightly at cross-purposes. “Neither side will grant all the non-empirical assumptions that the other needs in order to make its case.” While each may hope to “convert” the other to his or her way of seeing science and its problems, the dispute is not one “that can be resolved by proofs.” Kuhn quoted the theoretical physicist Max Planck who said: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”

03/7/17

Between a Rock and a Hard Place

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Terry Lynch is an Irish physician and psychotherapist who challenged the commonly held view that psychiatric disorders are legitimate brain disorders. He did so in a brief video that had an interesting take on the issue. He showed where two of the organizations affiliated with the U.S. National Institute of Health (NIH) apparently have different opinions about whether several psychiatric disorders should be considered to be brain disorders.

In his video, “It’s official: Psychiatric diagnoses are NOT known brain disorders,” Lynch gave a screen capture from the “Brain Basics” educational resources page of the National Institute of Mental Health (NIMH). He highlighted the opening statement there, which says: “Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps us better understand and treat disorders.”  Further down the page is the following: “Through research, we know that mental disorders are brain disorders.” These disorders were said to include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and many others.

He also called attention to a second NIH Institute, the National Institute of Neurological Disorders and Stroke (NINDS). The official mission statement of NINDS is “to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.” On the NINDS homepage is search engine where you can search by disorder. Lynch proceeded to show that depression, bipolar and schizophrenia were not listed in the NINDS database as neurological disorders. ADHD does appear in the NINDS, database but was not mentioned by Lynch in his video. You can replicate what I’ve said here be searching the “Brain Basics” page on NIMH and the NINDS database here.

One response to the differences Lynch found would be to say that NINDS attends to neurological disease, while NIMH addresses a different kind of brain dysfunction, namely mental or psychiatric disorders. But that response doesn’t resolve the dilemma. Because the next question becomes what is the difference between neurological disease and mental/psychiatric disorder? Attempting to articulate the difference may have placed psychiatry in a sort of catch-22 situation.

Lynch addressed this dilemma in an essay he wrote, “Psychiatry: Between a Rock and a Hard Place.” His opening statement there was that contrary to their repeated claims of doing so, “psychiatrists do not treat known organic illnesses.” They do not treat known organic brain disorders, which are under the care of neurology and neurosurgery. He said emotional and psychological distress typically comes under the care of counseling or psychology. So where, then, does psychiatry fit in?

Psychiatry is caught between a rock and a hard place—somewhere between the medical specialties treating known brain diseases (neurology and neurosurgery) and the talk therapies of counseling and psychology. Psychiatrists, according to Lynch, invented terms such as “mental illness” or “mental disorder,” and made themselves the experts who would diagnose and treat said illness/disorder. “They have fed the public with unsubstantiated ideas about neurotransmitters, chemical imbalances and brain disorders, ideas which the public have generally believed wholeheartedly.”

The challenge for psychiatry has been to carve out its own distinct identity. Claims that depression and other psychiatric diagnoses are biological illnesses are crucial to psychiatry’s identity and its unmerited position at the top of the mental health pyramid. These assertions separate psychiatry from the talk therapies and ensure that psychiatry has first claim to these “diseases” and the people they diagnose as having them.

He said psychiatry wants to be more closely aligned with the respected medical standing of neurology than to psychology or counseling. But it has to be seen as distinct from neurology to maintain a separate identity. “Specializing in ‘mental illnesses’ and ‘mental disorders’ provides the needed distinction.” Towards that end, Lynch said psychiatry has convinced the general public (and perhaps themselves) that psychiatric disorders are biological illnesses. In the process, they have side stepped “the fact that there is no reliable corroborative scientific evidence for this.”

For over a century, psychiatry has reassured the public that both the necessary understanding and more effective solutions lie just around the corner. “Bear with us, we are almost there,” psychiatry’s catchphrase for the past 100 years and more, buys them more time, every time.

Lynch thought psychiatry would confront a nightmare of their own making if it ever connected brain abnormalities to psychiatric diagnoses. If structural or functional brain abnormalities were ever found to be associated with psychiatric diagnoses, care of those individuals would likely be transferred away from psychiatry to neurology—“a specialty that deals with known brain abnormalities.” He said precedent within medicine would dictate that responsibility for those patients would be transferred to neurology or some other relevant specialty.

Given this, Lynch thinks the best position for psychiatry is to stay exactly where it is. As long as there are no reliable biological abnormalities identified, there is no threat to their position. By claiming that mental disorders are rooted in biology, psychiatry has set itself apart from talk therapies. “As long as no biological abnormalities are reliably identified, there is no threat that their bread and butter will be removed from them to other medical specialties.” Maintaining the myth that biological solutions are imminent, satisfies the public and preserves it’s position.

“If biology isn’t seen as central to the experiences and behaviours that have become repackaged as so-called “mental illnesses,” what special expertise can mainstream psychiatrists claim to possess?” So when psychiatrists defend their pronouncements on depression or any other psychiatric label, they are not just defending a diagnosis. “They are defending themselves, their ideology, their modus operandi and ultimately, their status and role in society as the perceived prime experts in mental health.”

Lynch is not alone in his views of psychiatry and diagnosis. There are clear echoes of the thought of Thomas Szasz in what he says. Peter Breggin, Joanna Moncrieff, Robert Whitaker, Peter Gøtzsche, David Healey, Sami Timimi and others would agree with parts, if not all, of what he asserts. Here, for example, is a blog article by Chuck Ruby for the International Society for Ethical Psychology & Psychiatry (ISEPP), “Blue Illness.” Reflecting on an article that affirmed depression was a mental illness, Ruby noted that for decades, attempts have been made to demonstrate the brain-pathology basis of depression.

Despite the billions of public dollars invested in this research, no such evidence of brain pathology has been discovered. The only thing this research has shown is that our experiences and behaviors are mirrored by changes in the brain. This is something we already knew. Yet, instead of giving up the search and redirecting those monies to more worthy research of real diseases, the mental health industry repeats the worn out pronouncement that discovery is just around the corner! Ironically, if such a discovery came, wouldn’t depression then fall within the medical specialty of neurology, the real medical specialty that studies real brain illnesses?

In the concluding paragraphs of their book, Psychiatry Under the Influence, Robert Whitaker and Lisa Cosgrove wrote that from a scientific standpoint, psychiatry is facing a legitimacy crisis. “The chemical imbalance theory is collapsing now in the public domain.” The former director of the NIMH, Thomas Insel, has written of how second generation psychiatric drug are no better than the first, “which belies any claim that psychiatry is progressing in its somatic treatment of psychiatric disease.”

The disease model paradigm embraced by psychiatry in 1980 has clearly failed, which presents society with a challenge: what should we do next?

Terry Lynch is right. Psychiatry is between a rock and a hard place. But save your sympathy for the patients who are there with it.

07/2/14

Thor’s Psychiatric Hammer: Antidepressants

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60 Minutes broadcast a segment on treating depression in February of 2012 that is still causing ripples of controversy. Two of the individuals interviewed, Irving Kirsch, a Harvard psychologist and Walter Brown, a psychiatrist with Brown University, challenged the two accepted pillars of current depression treatment. Kirsch said: “The difference between the effect of a placebo and the effect of an antidepressant is minimal for most people.” According to Brown, “The causes of depression remain a mystery.”

The chemical imbalance theory, which has guided the pharmaceutical industry in developing new drugs since the 1960s, is “probably incorrect.” Brown added that the experts in the field, the academic people who do research on drugs, now believe that the chemical imbalance theory is “a gross oversimplification.” If the neurotransmitters serotonin, norepinephrine, dopamine have anything to do with depression, “it’s of a minor role and probably sets the stage for depression. But they’re not the cause of depression. I think we know that now.”

Yet the chemical imbalance theory is still widely taught in medical schools. Many psychiatrists and mental health professionals still believe it. “The problem in psychiatry is that we don’t have a lot of tools. And if the only tool you have is a hammer, you treat everything as if it is a nail.”

Irving Kirsh has been doing research into the placebo effect for over 35 years. His original research intent with antidepressants was to evaluate the size of the placebo effect with antidepressants. He was a believer in the efficacy of antidepressants and he used to refer people to get antidepressant prescriptions. “I didn’t change the focus of my work onto looking at the drug effect until I saw the data from our first analysis.”

In a 1998 study, Kirsch found that 75% of the response to antidepressants was duplicated by placebo. He did a follow up study in 2002, where he analyzed the data submitted to the FDA for the six most widely prescribed antidepressants approved between 1989 and 1999: Prozac (fluoxetine), Paxil (paroxetine), Zoloft (sertraline), Effexor (venlafaxine), Serzone (nefazodone), and Celexa (citalopram).  He found a small but significant difference between the antidepressant drugs and inert placebo. “If the drug effect is as small as it appears … then there may be little justification for the clinical use of these medications.”

Leslie Stahl challenged Kirsch, saying that people are getting better by taking antidepressants. He agreed. “People get better when they take the drug. But it’s not the chemical ingredients of the drug that are making them better. It’s largely the placebo effect. . . . The only place where you get a clinically meaningful difference [with an antidepressant] is at these very extreme levels of depression.” The placebo effect is stronger with mild depression.

Both Kirsch and Stahl cautioned that antidepressants should not be stopped cold turkey. Leslie Stahl said that individuals who take antidepressants, and feel better as a result, will likely continue to take them. But she worried about the side effects. For some people there are serious side effects. “And if a sugar pill is just as good, how can we keep prescribing these pills?”

For more information on antidepressants, see: “Antidepressant Withdrawal or Discontinuation Syndrome?” and “Antidepressants: Their Ineffectiveness and Risks” under the Resources: Counseling Issues menu.