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.
While pharmaceutical companies claim they spend 30 billion dollars a year on research, and this conjures images of bench scientists peering through microscopes searching for the next miracle drug, we now know most of that money is directed toward a wildly successful systematic misinformation campaign that has fooled doctors and harmed patients. The only way the field of psychiatry will ever have credibility again is if we can trust that its science is actually science. The current system of funding psychiatric research has a built-in conflict of interest the industry has shown an unrelenting ability to exploit. It can never be fixed, only at best it can be regulated around the margins. A slide before grand rounds showing the presenter's list of drug sponsors won't do it. The fox can't guard the henhouse. Period. We need a radical solution.
A psychiatric colleague of mine (who asked not to be named in this article) has come up with the only credible plan I've heard that can save psychiatry. Pass a law. Make drug companies give half of its $30 billion in research to the National Institute of Mental Health. Let them dole out the money to independent scientists around the country. The topics of study would be chosen by scientific merit to provide honest answers. The designs employed would be rigorous. The results would be accurately reported, including negative results, side effects, and both short-term and long-term adverse responses. And we could ask questions drug companies don't want us to ask. Are expensive patented drugs really more effective than cheaper off-patent drugs, or naturalistic cures, or therapy treatments?
We need to reevaluate ALL the psychiatric literature with a fine tooth comb. All studies conducted by marketing companies under the false pretenses of ghost authorship must be discarded.We need to figure out how they made it into the best peer reviewed journals and plug that gap.It's urgent that we assess what misinformation has already made it's way into clinical practice, and correct it. If there are more Neurontins out there, every working psychiatrist needs to get the memo. Actually it would be good if they all read the memo about Neurontin. There are still docs using it for bipolar disorder.
Even legitimate studies funded by drug companies in academic settings need new scrutiny. It's human nature to want to please the patron who is writing you a six or seven figure check and helping to make your career. It could influence what might appear to be small things, like not emphasizing problems "just a few" patients had with the drug. Those studies and their data should be reviewed by independent experts. While studies funded by NIMH grants and other independent sources should be given more weight.Maybe drug-money-free studies should have their own prominent logo to alert the reader to their added value.
This pollution of science challenges the legitimacy of the profession. We can't trust psychiatrists' medication recommendations when their "knowledge base" is in large part industry propaganda dressed in scientific clothing.
Not that long ago, most psychiatrists were therapists. But the profession has reinvented itself in a generation because Big Pharma offered them a deal they couldn't refuse. "Doing psychotherapy doesn't pay well enough. I can see three or four patients in an hour if I focus on medications" wrote Carlat. "The income differential is a powerful incentive to drop therapy from our repertoire of skills, and psychiatrists have generally followed the money."
Psychopharmacology has another advantage for psychiatrists: it's turf no other mental health profession can encroach on, whereas therapy has been invaded by psychologists, social workers, and counselors, commoditizing the practice of therapy, and driving down the insurance companies rates of reimbursement A psychiatrist can easily earn $600 and hour doing 15-minute med checks, where a psychologist typically earns $65 dollars an hour as a Blue Cross Blue Shield provider. When I got out of graduate school psychiatrists were earning about 50% more than psychologists. (A joke published in the APA Monitor at that time was "What's the difference between a psychologist and a psychiatrist? Answer: about $40,000 a year.") But now, psychiatrists can earn a 1,000% more.
Big Pharma has made psychiatrists rich, and now they can't live without it. If psychiatrists were not giving out samples and writing prescriptions for this industry's products... what expertise would they have and how could they earn a living? Big Pharma owns them.
Will incidents like the Neurontin scandal lead to fundamental reform? I doubt it. I mentioned the Neurontin debacle to an Ivy league affiliated psychiatric colleague yesterday. He seemed unimpressed. Waving his hand dismissively he said, "Neurontin doesn't work for bipolar disorder. We all know that now," as if it were yesterday's news. "But we're finding it works for anxiety," he added cheerfully. Really, says who? Shrugging off their half-billion dollar fine, it appears Neurontin's manufacturer is now pushing a new off-label use: anxiety. Big Pharma hasn't missed a beat, and psychiatry continues to march to it.