GETTING to the truth that lies behind the widely promoted and, apparently, scientifically validated view that depression derives from a chemical imbalance in the brain may seem a daunting task. But to Professor Kirsch, author of this impressive book, it appears to have been an enjoyable ‘feather-ruffling’ exercise. From the book’s bold title right through to the final paragraph under the heading, “Don’t ask, don’t tell”, Professor Irving Kirsch’s use of the Hans Andersen metaphor is surprisingly apt while the underlying message is seriously disturbing.
Kirsch’s book is an account of how, with meticulous research and a firm resolve to find answers, he gathered documented data from the Food and Drug Administration’s (FDA) vast vaults of unpublished material on clinical drug trials, using the Freedom of Information Act to do so. Although Kirsch originally set out to test the placebo effect in treatment of depression, he sensationally stumbled over enlightening data on the ineffectiveness of antidepressant drugs when compared to therapeutic interventions (chiefly cognitive-behavioural therapy, as it is evidence based). His resolute tenacity led him to analyse clinical trials involving over 3,000 depressed patients, which has resulted in astonishing fact after fact falling over each other on every page. The answers Kirsch arrived at plainly show that strong prescription drugs for depression offer only marginal improvements over placebo.
His book gives details of how President Bush Snr signed bills allowing the FDA to charge drug companies fees to evaluate new products. Ironically, instead of helping to smooth the process of getting much needed healing drugs onto the market quicker, which was the intention, this action enabled ethical boundaries to be breached by seemingly unscrupulous industry executives keen to line their own pockets. Canny drug companies saw this as a loophole in their favour: as they commissioned the research, the power to publish only the positive studies lay in their hands – thus benefiting their profit margins. Hence, in similar vein to the Emperor’s fabricating tailors, representatives of the pharmaceutical industry appear to have wasted no time in weaving their marketing magic to put the best gloss on their merchandise.
Early on, Kirsch kindly issues a warning that the technicalities of clinical trials and subsequent number crunching may prove a little difficult for the layperson to grasp. What comes across in his surprisingly easy-to-read and often entertaining text is that he agrees with clinical practice evidence. Even his own meta-analysis in the book shows that the administration of antidepressants can offer meaningful improvement in a patient’s life. What Kirsch is concerned about is why they work, when they do. To illustrate his point, he lists some very vile brews and torturous practices that have been tested throughout history in clinical practice. For instance, lizard’s blood and crocodile dung were particular favourites, while dolphin’s genitalia and frog’s sperm were also cast into the cauldron. Kirsch quotes Morris and Shapiro’s 1978 study that found many patients were “purged, poisoned and punctured, blistered, bled and leached” and “if the patients weren’t killed by these treatments, they were deemed to have made them better”. So, convoluted concoctions seem to have worked equally as well in the Emperor’s days as the ‘pill for every ill’ appears to do today.
However, the main point Kirsch makes in his book is that true comparisons of effectiveness cannot exclude placebo effects from the statistical data. For instance, one graph highlights results that show little improvement from patients given placebos, and only marginal improvement in the response of chronically depressed patients who were administered strong drug doses. Why, he asks, is there is such a small difference in statistical evidence when comparing heavy-duty drugs to the apparently ineffective placebo? One of the answers repeatedly underlined (and one which the human givens perspective has confirmed since its inception) is that people appear to gain benefits simply as a result of being treated. For example, in a Dutch study on medication for ulcers that Kirsch unearthed, patients whose doctors administered four doses a day were understood to “improve at a significantly greater rate” than those given the same medication twice a day. However (and here’s the crunch), what both patient groups had taken were placebos.
Kirsch’s attempts to act in an ethical manner are admirable and his book details the extreme lengths he goes to in order to ensure that his extracts from studies are fair – because, as he shows, even though studies are carried out carefully, they may not yield true answers. For instance, double-blind studies of antidepressant drugs are commonly not double blind in practice, as patients very often know when they are taking a placebo or active drug. When asked how they know what they are taking, when even their doctor doesn’t know, their answer is inevitable: drugs give side effects. If patients don’t experience side effects, they suspect that they have been given a placebo and so may sink back into depression. However, those who do experience side effects are more likely to think that they are ‘getting something for their money’; therefore, improvements follow. Thus, in spite of (and, in many instances, because of) dangerous and, at times, life-threatening side effects, being administered medication by someone in authority satisfies a need in a depressed person. In this case, it is the emotional need for attention.
Thankfully, Kirsch reassures his readers that guidelines issued by organisations such as the American Psychiatric Association (APA) and the UK’s National Institute for Health and Clinical Excellence (NICE) encourage health professionals to act in good faith when assisting a depressed person back to health. However, it is somewhat disturbing to read that APA and NICE can only ‘require’ and ‘request’ data commissioned from the drug companies – and that these requests are often defiantly refused. Even when the data are handed over, it is only after they have undergone rigorous analyses known within the industry as ‘cherry picking’, ‘salami slicing', ‘pooled analysis’, ‘assay sashaying’ and comparison controls – all tricks of the trade to enable positive reports to be published rather than negative ones. Equally alarming, Kirsch found that information on trials deemed of ‘no value’ (ie data that produced negative results) was deliberately hidden by the FDA.
Kirsch’s book reveals startling evidence of how these important organisations, initially set up to act in the best – and legal – interest of public health, appear to end up adhering to the whims of a profit-greedy industry instead of serving the doctors whose intent is to heal. Kirsch writes of some quite disturbing stumbling blocks he faced in his effort to give a fair representation of the data. For instance, certain drug trials (for Seroxat, Lustral and Cipramil), were missing data – even in the FDA medical and statistical reviews. Similarly worrying, he found that only two studies showing positive results are required to show that a drug works, yet any number of studies can be commissioned until two that produce positive results are achieved (presumably after the ‘rigorous analyses’ described above) and those positive studies can be published multiple times.
Another serious concern Kirsch raises in his book is the chemical-imbalance theory. He questions why this theory was so widely accepted when the only controlled scientific studies on it were completed by doctor–researchers David Healy and Michael Shepherd, who could find little direct evidence for it and concluded that it was a mistaken belief: their work was ignored. Also, even though during the last 50 years researchers have tried to find more direct evidence for the chemical-imbalance theory of depression, they have failed. Kirsch even goes as far to say “Much of the evidence found is contradictory or runs counter to the theory”. Mind boggling!
Now that many people, from academics to tabloid journalists and the general public have been made aware of the placebo effect and the ‘dirty little secrets’ that Kirsch highlights, there’s a grim question that lingers. Are those acting on behalf of public health turning a blind eye to double-blind studies in an effort to line their own pockets with cash commissions and flyaway freebies? If Kirsch and other academics are, time after time, drawing attention to the dearth of facts to support the chemical imbalance theory, then is it not time for the ethical diligence of the drug companies be called into question?
Since its publication The Emperor’s New Drugs has helped to usher in sweeping changes in the way prescriptions are handled by those who practice ethically. And, apart from encouraging doctors to offer alternative treatments to antidepressants, Kirsch’s research has also led to continued fervent debate on the entire practice of prescribing. His work has certainly played the Emperor’s tailors at their own game.