DRUG BUST by Alan Cassels

Has there ever been a period when you flew off the handle over little things? Needed less sleep? Felt irritable? Answered yes to any of these? Now ask yourself this: “Is it really depression or could it be bipolar disorder?” These questions are designed to suck you into the world represented by a four-page ad promoting AstraZeneca’s drug Seroquel, the top-selling antipsychotic in the world. And what a crazy world it is.

A recent report on US prescribing trends showed that the new generation of “atypical” antipsychotic drugs, including Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine) and Risperidal (risperidone), is now the biggest money making class of pharmaceuticals in the world. Americans alone spend upwards of $14.6 billion per year on these drugs – an amount that beats out the Godzilla cholesterol-lowering market – a fact as deeply puzzling as it is disturbing. I mean, have we all gone completely and utterly bonkers? Yes, chalk me up as being irritable.

I remember watching the trends in antipsychotic prescriptions starting to rise a few years ago and wondered what was fuelling it. I found that schizophrenia affects only maybe 1.5 percent of the population. How then did these drugs, originally made for schizophrenia, ever become the most lucrative therapeutic class of drugs in the world? The easy answer in three words is: “Bipolar spectrum disorder.”

Classic bipolar disorder, sometimes called manic depression, is really a very serious, lifelong mental illness. It involves dramatic swings in mood that often last for days and weeks, oscillating between mania and depression. Yet its new variant, known as Bipolar II, has snuck up on us and surpassed classic bipolar, with the definitions having been widened to include people having at least one hypomanic and one major depressive episode. The depressive episodes are more frequent and intense than the manic ones so it’s often labelled ‘bipolar depression’ and part of the ‘spectrum.’

How many people suffer from some kind of bipolar disorder? Some experts say it’s around one percent of the population and others say it affects somewhere between five to 10 percent of the population. Who is right?

Well, it depends. Makers of antipsychotic drugs would certainly favour the larger number and the ‘spectrum’ where up to 10 percent of the population might become a patient. AstraZeneca hit the goldmine in October of 2008 when Seroquel become the first medication approved by the FDA to treat both “depressive and manic episodes associated with bipolar.” And there go the floodgates.

To get some clarity about what is happening, I called Dr. Joel Paris, a psychiatrist and professor at McGill University in Montreal and the author of numerous books including Prescriptions for the Mind and The Use and Misuse of Psychiatric Drugs. Dr. Paris has been openly critical of the expansion of bipolar disorder for some very good reasons, the most important one being that the proper trials of antipsychotics in “bipolar spectrum” patients have not been done.

As with any issue relating to expanding disease definitions, there is the risk that a large number of people may face the dangers of the drugs and not achieve any benefit because they don’t really have the disease the drug treats. Dr. Paris refuses to accept what has become a common perception among his colleagues that “everything is a variant on bipolar disorder, where every mood swing is being interpreted as bipolar.”

In his opinion, “If somebody is moody or irritable, it doesn’t mean because you can observe it, that there is a disease process happening. Bipolar spectrum means you don’t have mania or hypomania either. You just have mood swings. Sometimes the mood can swing by the hour. Not by the month. So classifying that as bipolar is totally unjustified.”

A lot of the overzealous use of antipsychotics comes down to how mental health is screened and labelled. According to Dr. Paris, there are many variants to human mental health, however, as he notes, “Calling everything bipolar is just plain wrong: Calling a bird and a bat the same thing is just wrong.”

Dr. Paris agreed that much of this inappropriate labelling is fuelled by the pharmaceutical industry, but that’s not the whole story. He says that pharma is just taking advantage of something that was already happening in psychiatry. “If the psychiatrists weren’t already attuned to giving everyone a medication, the drug industry wouldn’t be so successful,” he says.

Another reason bipolar might be so widely diagnosed is because of the Mood Disorders Questionnaire (MDQ), the most widely studied screening questionnaire for bipolar disorder. You might think if you were going to give people an incredibly powerful psychiatric drug, you’d have a foolproof system to identify patients. How well does the MDQ work? One study of over 500 psychiatric outpatients found that the positive predictive value – the probability that the person has bipolar if they get a positive score on the test – was around 30 percent. Another way to say this is that the test only pinpoints who actually has the condition only about a third of the time. The test lists all kinds of bipolar symptoms, but it doesn’t define them in terms of a time scale, a fact that has been crucial in having personality disorders become easily rebranded as bipolar disorder.

Let’s say you have actual bipolar disorder; do the drugs like Seroquel actually work? Dr. Paris says the drugs do help some people, but that the old standby treatment is lithium, which has been in use since the 1970’s.

In terms of the safety of the new generation of antipsychotic drugs, you’d have to look hard to find a class of drugs currently on the market that have more toxic and damaging effects than the antipsychotics. Again, for people who are truly psychotic, schizophrenic or bipolar, these newer generation drugs may make sense and help. But even for those people who are helped, there is an incredible cost in terms of potential for well-known adverse effects that can range from merely uncomfortable to life-threatening.

Heading that list is tardive dyskinesia, a very common, serious and sometimes irreversible adverse effect. Antipsychotic drugs cause people to make strange involuntary movements of the lips, tongue, and sometimes the fingers, toes and trunk. The person can become immobile and have difficulty chewing or swallowing. The drugs can cause diabetes and Parkinsonism where people have difficulty speaking or swallowing, lose their balance or experience muscle spasms, weakness or stiffness. Restless legs and the ‘jitters’ are also very common. People on antipsychotics are often listless, disinterested, drooling and depressed, which often results in another prescription, this time for an antidepressant. The well-known anticholinergic effects include confusion, delirium, short-term memory problems, disorientation, sedation and impaired attention. These are only the major negative effects; there are many others.

Despite this incredible range of widely recognized adverse effects, there are still experts who welcome the expanded definitions of bipolar. One such champion is Dr. Hagop Akiskal, a highly decorated and prominent psychiatrist at the University of California, San Diego. Unlike Dr. Paris, he happens to have close ties to pharmaceutical companies such as Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and GlaxoSmithKline and would be considered a ‘Key Opinion Leader,” the kind of doctor the companies love to have on the payroll.

While this influential psychiatrist might be pushing the boundaries of ‘bipolar spectrum,’ thinking it will ultimately benefit patients, this is a highly contested area of psychiatry. Many critics like Dr. Paris say that when the boundaries are too wide, it means many patients are either misdiagnosed or over-medicated with these powerful drugs and doctors should be cautious and conservative.

It’s true that a lot of the latest antipsychotic R&D is funded by the manufacturers and much of it does little more than find niche markets for their drugs. A recent court case against Seroquel’s manufacturer AstraZeneca revealed that clinical trials themselves were becoming a form of camouflaged marketing. In 1997, a researcher at the University of Liverpool asked AstraZeneca for research funds for a study he was planning. The company official apparently replied that “R&D is no longer responsible for Seroquel research – it is now the responsibility of Sales and Marketing.”

Say no more.

For Dr. Joel Paris, the worst part of the story is the marketing and use of these drugs in children. He says bipolar disorder doesn’t exist in kids, but psychiatrists often treat them as if it did. “A moody, impulsive child becomes a moody, impulsive adult. They do not develop classical mania. That’s why you have to use the term ‘bipolar spectrum disorder’ in order to justify treating them as a ‘bipolar,’” he says. “And then they get the drugs.” Last year in Canada, nearly 700,000 prescriptions for such antipsychotics were dispensed for kids under 13.

So back to the central question that launched me on this tirade: Why is a drug like Seroquel – US sales in 2009 were almost $5 billion – the fifth biggest revenue-generating drug in the US? Is it because experts are expanding the definitions of bipolar, using screening tools that are accurate only about a third of the time or working as paid spokespeople for the drug companies? Is it because psychiatrists are more than willing to prescribe drugs they know to be dangerous to people for whom those drugs have not been tested?

It is all of those things as well as the phenomenon we’ve seen dozens of times before: we’ve allowed marketing to masquerade as science. Who wouldn’t feel irritable and ready to fly off the handle? Maybe it’s about making all of us a bit more crazy and ready to swallow the next pill being offered.

Alan Cassels is a pharmaceutical policy researcher at the University of Victoria. Read his other writings at www.alancassels.com