GlaxoSmithKline’s corruption

GlaxoSmithKline
(Photo credit: Ian Wilson)

The details are simultaneously exactly what you’d expect and shocking.

And some people wonder why we’re reluctant to embrace the latest and greatest pharmacological fad. Keep all of this in mind next time someone suggests that medicalizing addiction treatment will improve professionalism, ethics and reliance on scientific evidence.

Sham advisory boards:

Glaxo also used sham advisory boards and speakers at lavish resorts to promote depression drug Wellbutrin as an option for weight loss and a remedy for sexual dysfunction and substance addiction, according to the government. Customers were urged to use higher-than-approved dosages, the government said.

Phony continuing education programs:

GSK paid millions to doctors to promote the drug off-label during meetings sometimes held at swanky resorts, the government said. The company relied on pharmaceutical sales reps, “sham advisory boards,” and continuing medical education programs that appeared independent but were not.

Misleading doctors:

The company went to extreme lengths to promote the drugs, such as distributing a misleading medical journal article and providing doctors with meals and spa treatments that amounted to illegal kickbacks, prosecutors said.

Bribing doctors:

“GSK’s sales force bribed physicians to prescribe GSK products using every imaginable form of high priced entertainment, from Hawaiian vacations to paying doctors millions of dollars to go on speaking tours to a European pheasant hunt to tickets to Madonna concerts, and this is just to name a few,” said Carmin M. Ortiz, U.S.attorney in Massachusetts.

Widespread:

Crimes and civil violations like those in the GlaxoSmithKline case have been widespread in the pharmaceutical industry and have produced a series of case with hefty fines. One reason some have said the industry regards the fines as simply a cost of doing business is because aggressively promoting drugs to doctors for uses not officially approved — including inducing other doctors to praise the drugs to colleagues at meetings — has quickly turned numerous drugs from mediocre sellers into blockbusters, with more than $1 billion in annual sales.

Stories have noted that Pfizer agreed to a $2.3 billion settlement in 2009. Also, Johnson & Johnson settled with Arkansas for $1.2 billion for several violations, including:

…for not disclosing the risks of the antipsychotic Risperdal.

Withholding data on Paxil:

GSK allegedly participated in the publishing of medical journal articles that stated paroxetine was effective in patients under 18, when, in fact, the data showed that the opposite was true. At the same time, the company withheld study data in from two other studies in which Paxil also failed to demonstrate efficacy in treating depression in patients under 18, according to a press release from the Justice Department.

Kept safety issues secret:

…the company kept secret data on raised cardiovascular effects.

Emotional pain without context

MRI coronal view of the hippocampus
MRI coronal view of the hippocampus (Photo credit: Wikipedia)

Siddhartha Mukherjee provides a brief history of the serotonin hypothesis of depression, its demise and why dismissing serotonin may be an “overcorrection.”

Part of this story is an emerging theory of depression:

A remarkable and novel theory for depression emerges from these studies. Perhaps some forms of depression occur when a stimulus — genetics, environment or stress — causes the death of nerve cells in the hippocampus. In the nondepressed brain, circuits of nerve cells in the hippocampus may send signals to the subcallosal cingulate to regulate mood. The cingulate then integrates these signals and relays them to the more conscious parts of the brain, thereby allowing us to register our own moods or act on them. In the depressed brain, nerve death in the hippocampus disrupts these signals — with some turned off and others turned on — and they are ultimately registered consciously as grief and anxiety. “Depression is emotional pain without context,” Mayberg said. In a nondepressed brain, she said, “you need the hippocampus to help put a situation with an emotional component into context” — to tell our conscious brain, for instance, that the loss of love should be experienced as sorrow or the loss of a job as anxiety. But when the hippocampus malfunctions, perhaps emotional pain can be generated and amplified out of context — like Wurtzel’s computer program of negativity that keeps running without provocation. The “flaw in love” then becomes autonomous and self-fulfilling.

He proposes an alternative understanding of the role serotonin may play:

An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire. Rather, it appears to change the wiring itself. Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits.

This still doesn’t explain the variation in responses to psychotropics. He acknowledges as much and alludes to the need for new typologies of depression. (Remember the dark ages when we talked about endogenous vs. exogenous depressions?)

The layers of speculation can obscure or illuminate just how crude our understandings of depression and the brain are. This, along with the history of psychiatric fads and abuses, makes one wonder if we should proceed a little more cautiously and work a little harder to capitalize on non-pharmacological tools like exercise and social support.