We know that corporations can show few scruples in hiding the damage done by their products. Cigarette makers hid the link to lung cancer for decades. Energy companies and their political allies deny any link between burning fossil fuels and global warming. But no industry has been as systematic nor as successful as drug companies in infiltrating the knowledge base concerning their products. The results have been high profits. The top ten pharmaceutical companies in the Fortune 500 make more money than the other 490 companies combined.
Imagine this: What if every scientist studying global warming was paid by Exxon? New York would be underwater before anyone knew global warming even existed. Yet, that is exactly the state of scientific research in psychiatry. Over 80 percent of the psychiatric research studies conducted in academic medical centers are funded by the drug industry. And that's the good news. With increasing frequency, Big Pharma is paying marketing companies with no ties to academia to generate studies that put their products in the best possible light; they then pay academics to put their names on the resulting studies as authors, even though they had no participation in the research whatsoever. To see what results, take the example of Neurontin.
About 12 years ago, I noticed that many of my bipolar type II patients were being put on a new drug, Neurontin. None of my patients seemed to get much benefit from it, and most suffered side effects. Now, I understand why.
We now know from independent research--research not funded by drug companies--that Neurontin produces absolutely no benefit in the treatment of bipolar disorder. None. But then, why did we ever believe it did? The Neurontin story is a particularly egregious example of science run amok, but not an atypical one. Psychiatrists were falsely induced to prescribe a medicine that was both unsafe and ineffective.
The study that Warner Lambert used to prove Neurontin was effective for the treatment of bipolar disorder was flawed and titled toward positive results, according to a recent article published in the Archives of Internal Medicine. Even worse, evidence of adverse consequences in this study was suppressed: 73 patients in this trial had adverse reactions, and 11 patients died.
How did this happen? In 1993 Warner Lambert had a problem. Neurontin, their new anti-epilepsy drug, had been given only limited FDA approval for use only as a second line epilepsy drugs--it could only be used if other epilepsy drugs already on the market failed. "Neurontin was a turkey." Wrote Daniel Carlat in Unhinged. What to do?
The company hired marketing firms--not scientists--to produce scientific articles demonstrating the benefits of Neurontin for bipolar disorder, and paid physicians $1,000 a piece to allow their names to be listed as authors of the studies that they neither conducted nor wrote (and perhaps never even read).
While the FDA requires a reasonably high level of scientific evidence to approve a drug for the treatment of a specific condition, once the drug is approved, doctors are free to prescribe any drug for any condition, off label. To convince them to do this, weak or massaged data can be dressed up to prove a drug is effective, and no FDA scrutiny is required. It's a crime for a drug company to market drugs to doctors for off label purposes, but that's exactly what happened. Marcia Angell, former editor of the New England Journal of Medicine, wrote: "the company had carried out a massive illegal scheme to promote Neurontin for off label uses--mainly by paying academic experts to put their names on flimsy research."
Drug reps descended on practicing psychiatrists. Warner Lambert senior executive John Ford exhorted his reps to "hold their hands and whisper in their ears...Neurontin for bipolar disorder." He went further, encouraging them to exceed the FDA recommended dose of 1800 mg/day, adding "I don't want to hear that safety crap." Warner Lambert paid 430 million in fines for its deceptive and illegal marketing of Neurontin to psychiatrists.
Is Neurontin isolated incident? Academic ghost authorship of studies produced by marketing companies is standard procedure. In 2001, drug companies paid $7 billion to a thousand contract research organizations to produce data that put their drugs in a most favorable light. How deeply has this penetrated psychiatry? Some 57 percent of the published scientific articles about Zoloft, for example, were written by the marketing firm Current Medical Directions and ghost authored by academics who had no part in the studies. These articles appeared in top journals including the American Journal of Psychiatry and the Journal of the American Medical Association. "Thus, for at least one anti-depressant, the bulk of the medical literature was literally written by the drug company that manufactured the drug, which is about as glaring a manipulation of science as one can imagine," wrote Carlat. And in a New York Times op-ed piece Carl Elliot wrote, "Pharmaceutical companies promote their drugs with pseudo-studies that have little if any scientific merit."
There are many ways to put your finger on the scales. One is to simply not publish negative results. Not surprisingly, drug company sponsored research is four times more likely to produce positive results than independent research. Wrote Carlat: "If I relied on the published medical literature (and what else can I rely on?) it would appear that 94 percent of antidepressant trials are positive." However, using the power of the Freedom of Information Act, Erick Turner demanded the FDA turn over all antidepressant trial data, and reported in the New England Journal of Medicine that across all the studies only 51 percent of the results were positive. Essentially, you might as well flip a coin.
In The Emperor's New Drugs, Irving Kirsh who also used the Freedom of Information Act to get suppressed FDA research reports, found similar results: 40 percent of antidepressant clinical trial data had been suppressed because they showed negative results. "When we analyzed all the data--those that had been published and those that had been suppressed--my colleagues and I were led to the inescapable conclusion that antidepressants are little more than active placebos."
Not only has the effectiveness of psychiatric drugs been oversold, but the real harm they may be doing has gone mostly unreported. For example, according to an impressive array of evidence presented by Pulitzer Prize nominated investigative reporter Robert Whitaker in Anatomy of an Epidemic, antidepressants appear to increase the lifetime rates of rapid cycling in bipolar patients. So the drugs that provide short-term relief actually worsen the disease they are meant to treat in the long-term. The response has been to add mood stabilizers and anti-psychotics, which have their own often disabling side effects, to offset the long-term instability produced by the antidepressants. So suppressing findings doesn't just give us billion dollar placebos. It gives us patent medicine that may be doing real harm.
Psychiatry, to its credit, has not taken these shocking ethical breeches lying down. Recently, the field had brought in tighter regulations in direct response to this and other scandals. Grand rounds speakers now must disclose their drug company funders; doctors can no longer accept valuable gifts, trips, or lavish meals from drug companies; drug reps' access to residents has been restricted; the FDA puts all results on-line, including negative results. That's progress.
But we need to face facts: Psychiatric research has become corrupted, not around the margins, but at its core. The scientific evidence that underlies psychiatrists' day-to-day prescription decisions is really marketing propaganda packaged as science. As a result, we can no longer trust psychiatrists' judgments and recommendations. "Garbage in, garbage out" is an old research aphorism--if the data is biased the results will be too. In this case, garbage data may be putting garbage toxic chemicals into our patient's bodies. We don't know, and can't know, if the pill psychiatrists are pushing today is the next Neurontin, or worse.