 First edition, 2009 | |
| Author | Irving Kirsch |
|---|---|
| Subject | The efficacy of antidepressants |
| Publisher | The Bodley Head |
| Pages | 226 |
| ISBN | 978-0465020164 |
The Emperor's New Drugs: Exploding the Antidepressant Myth is a 2009 book by Irving Kirsch, arguing that the chemical imbalance theory of depression is wrong and that antidepressants have little or no direct effect on depression but, because of their common or serious side-effects, they are powerful active placebos. [1]
Kirsch is Associate Director of the Program in Placebo Studies and a lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center, [2] and professor emeritus of psychology at the Universities of Hull and Plymouth in the United Kingdom, and the University of Connecticut in the United States. [3] [4] His research interests include placebo effects, antidepressants, expectancy, and hypnosis. [2] He is the originator of response expectancy theory. [5]
While analyzing antidepressant trials as part of his research into the placebo effect, Kirsch realised that drug companies do not publish all of their disappointing antidepressant trial results, but most decisions about the efficacy of an antidepressant are based only on published results. Using the Freedom of Information Act, he and his colleagues acquired from the US Food and Drug Administration the unpublished trial results for six antidepressants. When the results from both published and unpublished studies were averaged, the researchers concluded that the drugs produced a small but clinically meaningless improvement in mood compared with an inert placebo (sugar pill). [6] [7] (Some researchers have questioned the statistical basis of this study suggesting that it underestimates the effect size of antidepressants [8] [9] and other studies have reached a range of supporting and conflicting conclusions.) [10] [11]
To determine whether their averaging of results was hiding a meaningful benefit to more-severely depressed patients by combining their results with those of moderately and mildly depressed patients, he and his colleagues undertook another study, this time of the four new-generation antidepressants for which all (published and unpublished) trial data were available, and concluded that the difference between drug and placebo effect was greater for more-severely depressed patients, and that this difference was clinically meaningful (but still relatively small) only at the upper end of the very severely depressed category. They attributed this difference to very seriously depressed patients being less responsive to the inert placebo. [12]
Kirsch also addresses the conclusions of STAR*D, which found that if one antidepressant doesn't work on a patient, another should be tried in its place, and then another, until hopefully one will be found to be effective. The 2004 study found that although only 37% of patients were helped by the first antidepressant tried, 67% had found some relief by the time they had tried the fourth. [13] Kirsch cites a 1957 study [14] in which volunteers were given a drug that induces nausea and one to treat nausea. If the anti-nausea drug failed to prevent nausea, they were given another. If that failed, another was tried; and so on. All volunteers experienced complete relief from nausea by the sixth treatment, yet every treatment was a placebo. He concludes that the results of the 2004 antidepressant study are also likely due to the placebo effect. [15]
Since the chemical-imbalance theory of depression is based on the efficacy of antidepressants, Kirsch concludes, "It now seems beyond question that the traditional account of depression as a chemical imbalance in the brain is simply wrong." [15] [16]
The European Psychiatric Association published a position paper in 2012 [17] that described Kirsch's argument as "misleading". The organization argues that
Marcia Angell's review of the book welcomes Kirsch's work as a long overdue application of the scientific method to a field lacking rigorous scientific analysis, stating "Kirsch is a faithful proponent of the scientific method, and his voice therefore brings a welcome objectivity to a subject often swayed by anecdotes, emotions, or, as we will see, self-interest." [18]
Psychiatrist Daniel Carlat called the book "an important book, with the reservation that Kirsch’s selective use of data gives him the appearance of an anti-antidepressant partisan." [19] He states that Irving's conclusions are "provocative but unconvincing", noting that many drugs such as benzodiazepines have been tested for antidepressant activity and found inactive. Carlat argues that if antidepressants were acting purely via a placebo effect, any benzodiazepines and other drugs would show activity as well.
In a 2012 episode of CBS's 60 Minutes featuring Kirsch and his book, host Lesley Stahl said, "The medical community is at war – battling over the scientific research and writings of a psychologist named Irving Kirsch ... Kirsch and his studies have triggered a furious counterattack, mainly from psychiatrists." [20]
After the program's airing, Jeffrey Lieberman, the American Psychiatric Association's president elect at the time, said, "Dr. Kirsch is mistaken and confused, and he's ideologically biased in his thinking. He is conducting an analysis and interpreting the data to support his ideologically biased perspective. What he is concluding is inaccurate, and what he is communicating is misleading to people and potentially harmful to those who really suffer from depression and would be expected to benefit from antidepressant medication. To say that antidepressants are no better than placebo is just plain wrong." [6]
Reviews in the lay press have been largely positive, [21] [22] and the book was shortlisted in 2010 for the Mind Book of the Year award. [23]
There have been two English-language editions of the book – one in the UK, one in the US – and it has been translated into Japanese, French, Italian, Turkish, and Polish. [24]
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.
Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, generalized anxiety disorder, and premenstrual dysphoric disorder. It has also been used in the treatment of premature ejaculation and hot flashes due to menopause. It is taken orally.
A placebo is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.
Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The effectiveness of sertraline for depression is similar to that of other antidepressants, and the differences are mostly confined to side effects. Sertraline is better tolerated than the older tricyclic antidepressants. Sertraline is effective for panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), and obsessive–compulsive disorder (OCD). Although approved for post-traumatic stress disorder (PTSD), sertraline leads to only modest improvement in this condition. Sertraline also alleviates the symptoms of premenstrual dysphoric disorder (PMDD) and can be used in sub-therapeutic doses or intermittently for its treatment.
Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and social phobia. The antidepressant effects may take one to four weeks to occur. It is typically taken orally. In some European countries, it is sometimes given intravenously to initiate treatment, before switching to the oral route of administration for continuation of treatment. It has also been used intravenously in other parts of the world in some other circumstances.
Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction, it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate release formulation, carries a higher risk of seizure than many other antidepressants, hence caution is recommended in patients with a history of seizure disorder. The medication is taken by mouth.
Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. Studies have shown that venlafaxine improves post-traumatic stress disorder (PTSD). It may also be used for chronic pain. It is taken orally. It is also available as the salt venlafaxine besylate in an extended-release formulation.
Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth.
Reboxetine, sold under the brand name Edronax among others, is a drug of the norepinephrine reuptake inhibitor (NRI) class, marketed as an antidepressant by Pfizer for use in the treatment of major depression, although it has also been used off-label for panic disorder and attention deficit hyperactivity disorder (ADHD). It is approved for use in many countries worldwide, but has not been approved for use in the United States. Although its effectiveness as an antidepressant has been challenged in multiple published reports, its popularity has continued to increase.
Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.
Agomelatine, sold under the brand names Valdoxan and Thymanax, among others, is an atypical antidepressant most commonly used to treat major depressive disorder and generalized anxiety disorder. One review found that it is as effective as other antidepressants with similar discontinuation rates overall but fewer discontinuations due to side effects. Another review also found it was similarly effective to many other antidepressants.
Gepirone, sold under the brand name Exxua, is a medication used for the treatment of major depressive disorder. It is taken orally.
Esketamine, sold under the brand names Spravato and Ketanest among others, is the S(+) enantiomer of ketamine. It is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine.
Management of depression is the treatment of depression that may involve a number of different therapies: medications, behavior therapy, psychotherapy, and medical devices.
Irving Kirsch is an American psychologist and academic. He is the Associate Director of the Program in Placebo Studies and a lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center. He is also professor emeritus of psychology at the Universities of Hull and Plymouth in the United Kingdom, and the University of Connecticut in the United States. Kirsch is a leading researcher within the field of placebo studies who is noted for his work on placebo effects, antidepressants, expectancy, and hypnosis. He is the originator of response expectancy theory, and his analyses of clinical trials of antidepressants have influenced official treatment guidelines in the United Kingdom. He is the author of the 2009 book The Emperor's New Drugs, which argued most antidepressant medication is effective primarily due to placebo effects.
Vortioxetine, sold under the brand name Trintellix among others, is an antidepressant of the serotonin modulator and stimulator (SMS) class. Its effectiveness is viewed as similar to that of other antidepressants. It is taken orally.
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
Dextromethorphan/bupropion (DXM/BUP), sold under the brand name Auvelity, is a combination medication for the treatment of major depressive disorder (MDD). Its active components are dextromethorphan (DXM) and bupropion. Patients who stayed on the medication had an average of 11% greater reduction in depressive symptoms than placebo in an FDA approval trial. It is taken as a tablet by mouth.
Michael Pascal Hengartner is an academic psychologist at the Zurich University of Applied Sciences who has published on the subject of antidepressants and in other areas. In 2022, he published a book called Evidence-Biased Antidepressant Prescription: Overmedicalisation, Flawed Research, and Conflicts of Interest. He has also published with other notable researchers such as Joanna Moncrieff and Irving Kirsch.