
The Prozac Paradox: 50 Years On, Why Is Mental Illness Skyrocketing?
The World Health Organization (WHO) estimates that 1 in 8 people globally—i.e., 970 million or 12.5 per cent of the world's population—live with a mental disorder today
I write this piece on the eve of 75 years since the birth of modern psychopharmacology and 50 years since the discovery of Prozac, once touted as a miracle drug to treat depression. Before the advent of DSM-III and the arrival of Prozac, cases of mental disorders were limited. However, with the introduction of more and more drugs, the incidence and severity of mental disorders have skyrocketed.
An Alarming Increase
The World Health Organization (WHO) estimates that 1 in 8 people globally—i.e., 970 million or 12.5 per cent of the world's population—live with a mental disorder today. In the US and UK, the percentages are 23.1 and 25 respectively, while the proportion of Indians suffering from mental illness at any given time is 16 per cent.
Humongous Consequences
The consequences of the rapid growth in mental illness are immense. According to the WHO, the burden of mental health problems in India is 2,443 disability-adjusted life years (DALYs) per 100,000 population. It also estimates the age-adjusted suicide rate per 100,000 population as 21.1.
The Most Common Disorders
Major Depressive Disorder (MDD) and Generalised Anxiety Disorder (GAD) are the most common mental health conditions. As per WHO estimates, 280 million people globally suffer from depression, 304 million from anxiety disorders, 40 million from bipolar disorder, and 24 million from schizophrenia.
A Soaring Burden
The Lancet, between 1990 and 2019, global DALYs due to mental disorders significantly increased from 80.8 million to 125.3 million.
A few pressing questions arise at this juncture:
I will attempt to answer these questions a little later. Suffice it to say, for now, that after the discovery in 1975 of fluoxetine—the first SSRI, marketed under the tradename Prozac—and its projection as a 'miracle drug," the following consequences ensued:
Prozac was sold as a 'magic pill" to treat depression and other mental ailments including anxiety disorders. But was it? The editorial of the May 2025 edition of the prominent medical journal The Lancet sums it up succinctly: 'But 50 years on from landmark developments in drug treatment (with the arrival of Prozac) that were the cause of so much hope, we remain a long way from providing the level of care that so many people need, and this need continues to demand the attention of the scientific and medical communities."
Psychiatric Bible Or Unreliable Dictionary
I begin with a brief account of the DSM—the so-called psychiatric bible—and its controversial role in the proliferation of mental illnesses. The DSM first appeared in 1952 as a crisp 32-page document when the Committee on Nomenclature and Statistics of the American Psychiatric Association (APA) published the first edition, DSM-I.
From those original 32 pages, the manual expanded to 494 pages in DSM-III, culminating in 1120 pages in the latest version, DSM-5-TR (Text Revision).
DSM-I bore a distinct Freudian imprint. It also drew from the seminal work of eminent European classifiers of the late nineteenth and early twentieth centuries—German Emil Kraepelin and Swiss Eugen Bleuler. Everything changed in 1980 with the publication of DSM-III.
DSM-III marked a significant shift: the classification of mental disorders moved from 'aetiologically defined illnesses" to symptom-based 'categorical diseases." This was ostensibly done to create a more standardised and reliable framework for diagnosis. Ironically, DSM-III ushered in an era of medicalisation and chemicalisation of mental illness. It contributed to an exponential rise in diagnosed mental illnesses, broadened the scope of psychiatric intervention, and fuelled a dramatic surge in the sales of psychotropic drugs.
The result? From fewer than 100 classifications of mental illness in DSM-I, the number swelled to more than 220 in DSM-5-TR—pathologising a wide range of human emotions and behaviours. The latest addition to this list is 'prolonged grief disorder."
Moreover, despite eight iterations of the DSM over seven decades, its diagnostic system—based solely on consensus among contributors—continues to suffer from a lack of both reliability and scientific validity. DSM diagnoses are based on agreement over clusters of clinical symptoms, not on objective laboratory measures.
Hands Off
Unsurprisingly, in 2013, Dr Thomas R. Insel, then Director of the National Institute of Mental Health (NIMH), announced that the agency would no longer fund research based on DSM criteria. Insel cautioned that the DSM's supposed precision and reliability had been overstated for decades: 'While DSM has been described as a 'Bible' for the field, it is, at best, a dictionary, creating a set of labels and defining each."
And, he added, it is not even a particularly good dictionary.
Complicity, Collusion, Or Blind Following?
Symptom-based diagnoses, coupled with the exponential increase in conditions attributed to brain chemistry, had a profound impact—resulting in a proliferation of drugs purported to treat or cure such disorders. While these medicines brought relief to some, for many they caused unmitigated side effects without meaningful improvement.
Nonetheless, the psychiatric community—emboldened by pharmaceutical claims of 'miracle" cures and slavishly adhering to DSM classifications—accelerated the push for ever more medication. Often, this occurred in tandem with pharmaceutical companies, for whom SSRIs, SNRIs, antipsychotics, and mood stabilisers became blockbuster profit-making drugs.
Pressure from pharmaceutical companies contributed to a massive rise in psychiatric prescribing and an increase in labelling patients to justify that prescribing. Critics of DSM-5 pointed out that: 'Seventy per cent of people serving on its committees to define specific diagnoses had financial ties to pharmaceutical companies—up from 57 per cent for DSM-IV."
Multibillion-Dollar Industry
It is difficult to accurately assess the annual sales and growth rate of the entire psychotropic drug market. Nonetheless, various estimates place the current market size at around USD 40 billion, expected to grow to USD 75 billion within the next decade.
It is now time to examine the birth and rapid expansion of psychopharmacology—particularly over the past five decades since the discovery of Prozac.
The Birth
We now live in the age of psychopharmacology. Such is the discipline's dependence on psychotropic drugs that, were they to be removed, psychiatry as we know it would collapse.
The key question is: when, where, and for which condition was modern psychopharmacology born?
The best estimate is 1949, with the serendipitous discovery by John Cade of the effectiveness of lithium salts in treating mania in bipolar disorder. Shortly afterwards came the synthesis of chlorpromazine in 1950 to treat schizophrenia—both marking foundational milestones.
But for me, psychopharmacology was truly born in 1949, when John Cade successfully treated ten patients with 'psychotic excitement" using lithium salts.
Those 75 Years
In the 75 years since, psychotropic drugs—particularly the SSRI class of antidepressants—have become blockbuster medications. Prescription rates have grown exponentially, gradually sidelining psychotherapy. How did this happen?
It's The Chemistry, Stupid
The aetiology of mental disorders is complex. Understanding it requires an integrated approach accounting for the interplay of multiple factors—genetic, neurochemical, environmental, social, and cultural.
However, this nuanced understanding was reduced to an oversimplified explanation following the arrival of DSM-III and the aggressive marketing of Prozac and Zoloft. Pharmaceutical companies popularised the so-called 'chemical imbalance theory," which proposed that mental disorders in general—and depression in particular—stem from imbalances in neurotransmitters (chemical messengers in the brain) such as serotonin, dopamine, and norepinephrine.
Yet this theory is far too simplistic. If it were entirely true, we would see far fewer cases of mental disorders today—especially depression and generalised anxiety disorder, which should have been virtually eradicated.
That has not happened. On the contrary, we appear to have entered an era defined by what some critics call a 'strategy of marketing diseases as an effective way of marketing drugs."
The Early Psychotropic Drugs
First came lithium, used to treat bipolar disorder, soon followed by antipsychotics for schizophrenia. In the 1960s, Iproniazid and Imipramine were introduced to treat Major Depressive Disorder (MDD), based on the 'monoamine hypothesis of depression."
At that time, the prevalence of mental disorders was relatively low, and so were the annual sales of psychotropic drugs.
The Arrival Of SSRIs
The seeds of SSRIs were sown in the late 1960s, when post-mortem studies showed decreased levels of serotonin in depressed individuals who had died by suicide. This discovery led the pharmaceutical company Eli Lilly to search for compounds that would selectively inhibit serotonin reuptake at transporter sites—thereby increasing serotonin concentrations in the synaptic cleft and stimulating postsynaptic receptors. This formed the basis of what became known as the 'serotonin theory of depression."
Prozac Unleashed
The journey of Prozac began on 8 May 1972, when Eli Lilly researcher Jong-Sin Horng discovered that the compound 'Lilly 110140" altered serotonin concentrations in the brain. Its efficacy as an antidepressant—with significantly fewer side effects compared to existing drugs—was demonstrated in 1975 by Wong and colleagues. This compound, fluoxetine, turned out to be a potent and selective serotonin reuptake inhibitor (SSRI).
This led to the birth of the first SSRI—fluoxetine—which was later given the trade name Prozac and approved as an antidepressant by the US FDA in 1987.
Soon after Prozac's introduction, several other SSRIs were approved, including sertraline (Zoloft®), citalopram (Celexa®), paroxetine (Paxil®), and escitalopram (Lexapro®).
The Miracle Pill
Prozac was marketed with much fanfare as a miracle pill for depression—promising greater efficacy and substantially fewer side effects than the antidepressants available at the time.
Books such as Prozac Nation and Listening to Prozac, along with pop culture, 'Prozac" musicals and repeated references in Hollywood films, helped propel Prozac to unparalleled commercial success. It became the most widely known—and most sold—psychotropic drug in history.
The Prozac Moment
Today, the name 'Prozac" serves as a shorthand for all antidepressants. The Oxford English Dictionary defines Prozac as: 'Prozac or fluoxetine hydrochloride, an antidepressant drug belonging to the group of selective serotonin reuptake inhibitor (SSRI) agents, used in the treatment of depression, obsessive–compulsive disorder, bulimia nervosa, and panic disorder."
The phrase 'Prozac moment" has come to mean a fleeting feeling of happiness—or forgetfulness. People also speak of a Prozac shot, a Prozac smile, or feeling 'better than well."
How, then, was humanity sold the miracle of Prozac? It's an interesting tale.
A Lot In The Name
David Healy, the well-known Professor of Psychiatry and expert on psychopharmacology, famously said: 'What made Prozac good was not that it was potent—which it really was not—but that it had really good marketing."
SSRIs are now often referred to as all-purpose 'happy pills", prescribed not just for depression but also for anxiety, obsessive behaviours, substance abuse, chronic pain, shyness, and even to help people feel 'better than well".
How did fluoxetine hydrochloride become the miracle 'happy pill" Prozac? The answer lies in branding and marketing.
Eli Lilly brought in Interbrand, a reputed branding agency, to commercially repackage the drug and distance it from everything associated with earlier antidepressants—'strong chemicals, side effects, withdrawal symptoms".
Interbrand coined the name 'Prozac":
'Pro" connoted positivity
'Z" suggested strength
'Ac" implied action
The result was a name—and a narrative—that transformed a modestly effective drug into a global phenomenon.
Pill-Popping Children
On 3 June 2003, the US FDA approved Prozac for the treatment of children aged 7 to 17. Notably, even before this official approval, between 1987 and 2002, millions of prescriptions for Prozac and its counterparts had already been written to treat emotionally disturbed children.
Cult Following
The introduction of Prozac—and the subsequent arrival of other SSRIs—led to an astronomical rise in the sale of psychotropic drugs, making them blockbuster medicines. Millions across the world embraced Prozac on a scale previously unseen in the history of psychopharmacology.
It would not be an overstatement to say that only two drugs have achieved such a cult following: Prozac, developed by Eli Lilly in 1975, and Viagra, introduced by Pfizer in 1987.
Lilly Blooms – The Age of Depression
For the pharmaceutical industry, the 1990s became the 'Age of Depression", with annual sales of Prozac and other SSRIs surging dramatically.
I'll return to that shortly. First, the Prozac story.
In 1988, its first year on the market, Prozac generated USD 350 million in sales—eclipsing all other antidepressants. By 1990, it had become a blockbuster drug, crossing the one-billion-dollar mark in annual revenue. At its peak in 1998, annual sales of Prozac reached USD 2.8 billion. In 2000, just before its patent expired, Eli Lilly reported worldwide sales of Prozac at USD 2.6 billion—25 per cent of its total revenue—making it the fourth best-selling brand-name drug that year.
Others Join The Party
Between 1991 and 2001, global antidepressant sales increased tenfold, reaching USD 11 billion and becoming the chief profit driver for the pharmaceutical industry over the decade.
In 2001, out of the USD 11 billion antidepressant market, the market share was distributed as follows:
Sertraline (Zoloft): 18 per cent
Paroxetine (Paxil): 16 per cent
Fluoxetine (Prozac): 14 per cent
Citalopram (Celexa): 13 per cent
Bupropion (Wellbutrin): 9 per cent
The combined market share of other antidepressants stood at 14.7 per cent, while tricyclic antidepressants had plummeted to just 2 per cent.
In the last two decades, the antidepressant market has continued to soar—reaching USD 20.1 billion in 2024, with projections of USD 27 billion by 2033.
Do Psychotropic Medicines Work?
It has been seventy-five years since the birth of modern psychopharmacology and fifty years since the arrival of the so-called wonder drug, Prozac. During this time, the number of psychotropic medications—and their sales—have exploded. But despite the claims of 'mind-fixers," the actual efficacy of these drugs in treating mental illnesses has not significantly improved.
What holds true for many of these drugs is even more true for Prozac, the so-called miracle pill.
Short Haul, Long Haul
Modern antidepressants were originally approved for short-term use—typically six to nine months—just enough to help patients through a crisis. But soon after approval, psychiatrists began prescribing them for long-term maintenance therapy.
And here lies a fundamental problem with psychotropic drugs.
Once a drug is discovered or approved, doctors across the world are free to prescribe it as they see fit. Unsurprisingly, despite the lack of robust long-term efficacy data, psychiatrists in India and globally have placed tens of millions of people on antidepressants indefinitely.
For example, in the late 1980s in the US, only 1 in 50 people received a prescription for an antidepressant in any given year—and even then, for just a few months. Today, that figure is closer to 1 in 7, possibly even 1 in 5, with an increasing number of patients remaining on medication for decades—often without any clear or sustained benefit.
I Rest My Case
My argument is not that psychotropic drugs—antidepressants, antipsychotics, mood stabilisers, and others—do not work. It is accepted that psychiatrists have little understanding of the aetiology of mental disorders, and they do not fully know how psychotropic drugs work, or why they sometimes fail. Yet, these medicines do help in a significant number of cases. They may not cure, but they help manage symptoms and offer relief.
That said, the consensus remains that in 30 to 50 per cent of depression cases, antidepressants do not work. In such instances, psychiatrists often label patients as 'drug-resistant." The efficacy of psychotropic drugs in treating more serious conditions like schizophrenia and bipolar disorder is equally disappointing, if not worse.
Medicine, Not Miracle
Prozac, along with other SSRIs and SNRIs that followed in its wake, was introduced to the world as a 'miracle drug"—a narrative fuelled by an unprecedented marketing blitz from pharmaceutical companies, books such as Prozac Nation and Listening to Prozac, and even musicals and Hollywood films. Decades have passed, and the reality is far more sobering.
SSRIs, like their predecessors, are simply medicines. They work for some, and not for others. Some studies have shown that SSRIs may be less effective than earlier antidepressants. Other long-term studies suggest that SSRIs are no more effective than placebos. Moreover, the milder the depression, the weaker the evidence that Prozac and its kin perform any better than a placebo.
Suffice it to say, Prozac not only sparked the fire but poured tonnes of fuel onto the cultural bonfire of 'better living through chemistry"—a promise that ultimately could not be fulfilled.
Moreover, SSRIs are not free from side effects—as pharmaceutical advertisements, costing hundreds of millions of dollars, misled the public into believing. Like all drugs, SSRIs come with their own risks: mental fog, suicidal ideation, loss of libido, and other sexual dysfunctions. They also cause withdrawal symptoms for many.
And the long-term side effects of SSRIs remain poorly understood.
To sum up: antidepressants and other psychotropic drugs can work—and do work—for some people, but not for others. They are life-saving for a few, but can be life-threatening for others. Additionally, what holds true for patients in the US does not necessarily hold true in India.
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It is time to accept that these are not panaceas. The search for a true cure for mental illness must continue. India must invest in Bharat-centric research into the aetiology and understanding of mental disorders, as well as their treatment. The era of symptom-based treatment is over. Period.
The author is a past member of GoI's National, Mental Health Policy Group and Central Mental Health Authority and is an India-based international impact consultant, and keen watcher of changing national and international scenarios. He works as president advisory services of consulting company BARSYL. Views expressed in the above piece are personal and solely those of the author. They do not necessarily reflect News18's views.
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Antidepressants Depression mental disorder
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New Delhi, India, India
First Published:
May 28, 2025, 14:51 IST
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