I had coffee with a drug company rep once. She gave me a textbook I’d wanted. In exchange, I sat and listened as she peppered her sentences with the company’s name. I stopped hearing what she was saying. Was she keeping count? Had she done this for so long she now did it without thought? “How are your twins?” she asked. Good memory. She’d seen me lumbering around the wards heavily pregnant a few years before.
To me, the reps all look the same: very pretty women wearing suits, great-looking guys who belong to weekend triathlon clubs, twinkling their ten-years-younger-than-me eyes. It’s a seduction. One by one they try to touch us with their food and their flattery and the name of their drug till it’s as familiar as family, till we trust it and them, till we choose X over Y.
Drug company reps play on doctors’ uncertainty, on our anxiety that we do not know. They play on our fear that we will do the wrong thing, the not-so-good thing, the out-of-date thing. They’ll buy you lunch, dinner, business-class plane tickets if you want. I don’t want. I won’t eat their food, answer their calls, read their propaganda or take their money. I don’t think racketeers have any place in a public hospital.
The new drugs they’re promoting (or “representing”, as they say) aren’t rubbish. Read the reports of the trials and you’ll see the drugs are more or less equivalent to our trusty old rat poison. Too much and you might end up collapsed under your table, bleeding out like a rodent. Not enough and you may clot up like a sausage. The main benefit was supposed to be that, unlike warfarin, the new drugs didn’t need to be monitored by frequent blood tests.
They’re expensive drugs and took some time to be approved. One drug company launched a website encouraging people to write to their member of parliament to protest the delays in approval. It bypassed the specialists and aggressively promoted its drug, dabigatran, to GPs, flooding consulting rooms with free starter packs and lunch. Patients loved it – no blood tests – and GPs prescribed it like crazy. But it turns out that dabigatran offers less protection against heart attacks than warfarin. And then one of the company’s own reports concluded that some patients who were taking dabigatran may need a bit of monitoring after all, just to check their blood wasn’t too thin and they wouldn’t bleed to death.
Some of the company’s employees sought to have the information quashed. “Can’t this be avoided?” one wrote. The in-house researchers were asked to please check again if the monitoring recommendation was really warranted. If doctors knew there was less protection against heart attacks, and on top of that if some patients needed blood tests after all, they might stop prescribing it! In the name of the dollar and of marketing something shiny-glossy new, in the name of sales achievements and your end-of-year bonus, can’t these facts be avoided, please?
The Pill Problem
I was at a party. The host stood up, thanked everyone for coming, toasted his family and then told us he had been diagnosed with depression. He turned his head away and pressed his fingers into his eyes. No one moved. “But it’s okay,” he said. “I understand that what I have is a disease, caused by a chemical imbalance in my brain.”
Worldwide sales of antidepressants make pharmaceutical companies tens of billions of dollars. Each year, 17 million scripts are written in Australia at a cost of more than $533 million. Eighty-five per cent of the scripts are written by GPs.
Many of the elderly patients on my ward, including those with severe dementia, are on antidepressants. Sometimes they have landed in my ward as a result of side effects: dizziness that leads to falls; delirium; precipitously low salt levels in their blood that can cause confusion, headaches and seizures. “You’re taking an antidepressant,” I’ll say. “Why was that prescribed to you?” They answer, “I’m taking a what?” or “My GP gave it to me years ago, when my husband died.” One of my inpatients was a man in his fifties who had suffered a major stroke and could no longer walk or speak with ease. He could no longer provide for his family. A doctor who covered the ward for me on the weekend suggested I start him on an antidepressant. “He was crying,” she said. “I think he’s depressed.”
As doctors, we want to be useful. Prescribing is a satisfying act: here I am, doing something.
The story of how antidepressants became the most widely prescribed and profitable drugs in the history of medicine is an interesting one. In the 1950s, a collection of symptoms was given the name “depression” and defined as a disease. In the following decades, drugs to cure this disease were marketed heavily, mostly on the strength of their hypothesised mechanisms of action. Pharmaceutical companies funded clinical trials and published the results of the ones that showed statistically significant benefits of drug treatment. The disease model was promoted as patient-friendly because it apparently countered the view of depression as a moral or personal failing. Data that linked the widespread prescription of antidepressants with a decrease in suicide rates were repeatedly cited. Key opinion leaders championed the drugs. National guidelines recommended the drugs be prescribed for patients who suffered severe depression; doctors extrapolated from that and gave them to everyone.
In the United States, the drugs are advertised on TV. The viewer is invited to ask their doctor for a prescription to fix their brain’s chemical imbalance, their lack of serotonin, their pain and misery, so that they can once again run on the beach with bleached teeth and nicely blow-dried hair. Unfortunately, the advertisements’ cartoons that depict the drug racing through your blood and smashing like a piñata against starving nerve endings are bullshit. There is scant proof in the neurosciences that this reductionist theory of chemical imbalance is correct. It is closer to myth than science. As is the idea that massive antidepressant prescription has led to a decrease in the rate of suicide. There is hard evidence that the belief in the chemical imbalance theory increases social stigma and the duration of symptoms. Mild to moderate depression is generally a short-lived experience which waxes and wanes.
Perhaps most importantly of all, recent re-evaluation of the trials has shown that these drugs do not work for the majority of patients who are prescribed them. Researchers used freedom of information laws in the US to uncover dozens of trials the pharmaceutical companies had suppressed. When they combined the published and unpublished trials, they found that half showed the drugs worked (barely) better than placebo and half showed they did nothing at all.
I do not think the psychic consequences of physical debility, loss, poverty or abuse are necessarily a disease called depression. I wish it were true that there was a safe pill that could ease ordinary misery. I’d prescribe it like crazy. I’d probably take it. But unfortunately the so-called antidepressant drugs have minimal benefit to the average individual who presents to a GP, have multiple side effects (including the possibility of a small increase in the risk of suicide) and are difficult to get off. I am glad that there are psychiatrists, because I’m not trained to treat people who cannot feel anything or cannot feel anything except pain – patients who want very much to die. If you feel this way, you should certainly seek help. If I think one of my patients is gravely depressed or suicidal, I ask my psychiatrist colleagues to see them, urgently. These are not the majority of the patients being prescribed antidepressants by their non-psychiatrist doctors and for whom – according to hard trial data – the drugs are as helpful as or less helpful than regular exercise, psychotherapy, St John’s wort or placebo. These patients may not need drugs. They may need social workers, psychologists, rehabilitation, a job, home help. Someone to talk to, someone who will listen.
There is another way to read the antidepressant story: pills mean big money for those who make and promote them, but for society they are cheap. If socially generated miseries are defined as diseases, the crushing responsibility of helping a country full of suffering citizens can be handballed to medicine. Social isolation, unemployment, violence, disability, poverty, racism and bullying need not be addressed. The cures for these causes of misery are neither simple nor easy, but our response to a person wh
o has lost everything has become “Give them a pill”. The page titled “What causes depression?” on the Beyond Blue website is illustrated with a large picture of an Indigenous Australian man. He is quietly beaming.
The Trouble with Miracle Cures
In 2013, when I read in The Guardian that antibiotics could cure chronic lower back pain, I thought it was some kind of joke. What next? Psychiatrists declaring that depression is caused by an infection of the heart and could be cured by penicillin?
I don’t normally keep my medical knowledge up to date with newspapers. Like most hospital doctors, I rely on meetings, conferences, corridor conversations and the heavyweight journals. But I needed a paper to present at journal club, so I looked for the original research.
The newspaper report was based on a double-blinded, placebo-controlled trial of antibiotics given to patients who suffered constant back pain and had MRI pictures that suggested vertebral disc inflammation. The results seemed astonishing: more than a third of the patients who took the antibiotics for 100 days showed marked improvement.
Lots of people with back pain have surgery and sometimes it’s successful. Neurosurgeons cut into your spine, in good faith, knowing it’s all they have to offer to treat your pain. But what if you could take three months of a standard sinusitis treatment instead? I emailed a neurosurgeon I know. He’d heard nothing about the trial and wondered if I was mistakenly referring to osteomyelitis (an acute infection of bone). I sent him the paper. He sent it around his department. That afternoon he forwarded me an email from one of the other neurosurgeons: “If this were truly paradigm-changing, it would have been reported in a more prestigious journal than this!”
A hypothesis is just a story put together from a number of facts with the gaps filled in. This story starts off with facts: some people with chronic back pain have MRI pictures that suggest a particular kind of inflammation of the vertebrae; some vertebral discs removed at surgery grow bacteria, including a skin dweller called Propionibacterium acnes. For the researchers’ story to work, P. acnes needs to lodge in a disc, cause pain, and then be obliterated by the antibiotic. They fill in the gaps like this: for years P. acnes was assumed to be a contaminant just catching a ride as the vertebral disc left the body. But when we brush our teeth or scratch at our skin, we send tiny sprays of bacteria into our bloodstreams. Usually our immune system destroys these bugs before they can lodge somewhere and cause damage, but when a disc is dislodged it causes inflammation of the bones around it. This inflammation causes extra blood flow, which delivers the bacteria. Vertebral discs are very low in oxygen, which is exactly the kind of environment in which P. acnes likes to grow. The bacteria therefore move into the disc and secrete propionic acid, which dissolves the surrounding bone and marrow and stops them healing. This causes pain. Kill the bug, the bones will heal and the pain will go away. It all adds up to a great story with a neat happy-ever-after ending.
In 2005, Barry Marshall and Robin Warren received the Nobel Prize for their work that proved a bacterium causes stomach ulcers. Initially, though, their studies were ridiculed and rejected. Gastric surgeons kept their operating theatres full, cutting out and discarding chunk after chunk of ulcerated stomach. Who could have believed that those deep ulcerations in the stomach lining – ulcerations that led to people bleeding to death or to cancer – had been caused by a bug? Changes in medical paradigms are slow and fraught: people lose their careers, their company shares, their standing. “If this is true,” my surgeon friend wrote about the findings of the back pain study, “a lot of neurosurgeons are going to find themselves out of work.”
Like most media beat-ups, there was more to this story than was initially reported. The researchers had hired a public relations company to launch their study results. There was no mention of the important point that most people with back pain don’t have MRI pictures of disc inflammation. Nor was there mention of the fact that at the end of the trial there was no reduction in the number of days any of the participants had to take off work because of pain. The methods were flawed: most of the patients who received antibiotics had very different MRI scans from those receiving the placebo. The researchers were accused of having serious commercial conflicts of interest: they’d opened a private clinic to treat back pain with antibiotics, coined a fancy acronym (MAST, for Modic Antibiotic Spinal Therapy) and launched a training academy. All of it based on a single, somewhat shaky study.
The infectious-diseases physicians urged caution. They are the hospital’s activists, forever reminding us that antibiotics are a precious resource. Spray the world with broad-spectrum antibiotics and you’ll breed resistant superbugs, and then we’ll be right back where we started: treating infections with fresh air and leeches. Sanatoriums in some countries are filled with patients who must be kept in isolation as their tuberculosis rots on despite treatment; patients in developed nations, in high-tech intensive care units, are dying from infections resistant to all known antibiotics. Every treatment has the potential to cause harm, but in the case of antibiotics it is not only to the individual – acute liver failure, for instance – but also to society.
A real paradigm change in medicine starts as a story that may one day be proven true. If that happens, the original storyteller becomes a prophet. But more often than not, the hypothesis proves false (think of megadose vitamin C, for instance). The story remains a distant tabloid miracle cure, rejected by the mainstream, practised on the fringes; the original storyteller is branded a quack.
Groups around the world are right now culturing all the vertebral discs they can get their hands on and organising larger, more robust trials.
I hope the story turns out to be true, but we’ll just have to wait and see. Until then, if you walk in the door with terrible back pain, most doctors won’t give you antibiotics, because we are only doctors: neither long-odds prophets nor quacks.
Crazy Pills
Last summer I was swimming at my local pool. It was almost midday and I knew I should get out and under cover to protect my skin, but the cool water and warm sun felt good, and I reasoned that I could probably do with a dose of vitamin D. I saw a woman in a full-body wetsuit make her way to the edge of the pool. She was also wearing socks, mittens and a mask, which left only a small circle of her face exposed. She adjusted her gloves and I heard her say to the woman beside her, “I wouldn’t wear this if I didn’t have to, for medical reasons.” I was dying to ask her what the medical reasons were. I looked down at my freckles and got out of the pool.
The following week, a patient told me that a GP–naturopath had put her on something called “The Marshall Protocol”. She asked for my opinion, and I said I’d never heard of it. She looked at me as if I were a child. “It’s about vitamin D,” she said. I started to sweat: was it one of those things I was supposed to know but could never remember, like the difference between anti-Ro and anti-La antibodies? The protocol dictated that she protect herself from sunlight for an indeterminate period – maybe more than a year – and avoid all foods containing vitamin D; apparently this would starve her bacteria and repair her immune system. “I’ve been trapped in my house with the blinds down,” she said.
Right now, vitamin D is being promoted with religious fervour. Vitamin C had a moment like this in the 1980s. For a while it could cure everything – cancer, influenza, heart attacks, HIV – and make us live to 150. When we were kids, my brother and I benefited greatly from this craze. The experts were saying that sugar caused hyperactivity but vitamin C was healthy. We’d bully our mother into buying those mega jars of tangy orange tablets that tasted just like giant Tic Tacs, and then we’d sit in front of the TV and eat them by the handful. To us, vitamin C was an endless supply of legitimate lollies.
In times of famine or in severe malabsorptive states, vitamin deficiencies cause real disease: lack of vitamin C causes scurvy, lack of B1 causes heart failure and neuropathy, lack of B12 causes anaemia and neurological damage. The ancient Egyptians knew that night-blindness (a
result of vitamin A deficiency) could be cured by eating liver. Rickets – where bones grow weak, soft and deformed – is usually caused by extreme vitamin D deficiency. In the eighteenth century, rickets was treated with a pottage of snail, worm and beer.
We get vitamin D from egg yolks, offal and oily fish, but the main source is produced in our body when sunlight hits our skin. Apparently we’re all a little vitamin D deficient because we spend too much time indoors: working, playing, hiding from the sun. This mild deficiency has been linked to everything from broken bones and falls to depression, cancer and heart attacks. Vitamin D tablets are the latest miracle cure-all. Go to a hospital or visit your GP and it’s more than likely that someone will test your level of vitamin D. In Australia we spend 150 million Medicare dollars a year on 4 million vitamin D tests. We argue about the magic level. Is it 50, 70 or 100 nanomols per litre of serum?
Vitamins and other supplements are big business – for the pharmaceutical companies that make them, the chemists that flog them (with sales worldwide estimated at US$68 billion a year) and the labs that test the levels in our blood.
For about a grand you can get megadoses of vitamin D pumped directly into your veins by an alternative health practitioner, while their colleague may claim it’s just food for bacteria. On the fringes, they’re saturating or starving you. Doctors meander somewhere in the middle, mostly recommending small doses for those with low levels.
True vitamin deficiencies are rare in the average, ambulant citizen of the developed world, yet more than a third of the population take some form of vitamin supplement – convinced something is missing.
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