The Rise and Fall of Modern Medicine (58 page)

Still, it would be most surprising if the therapeutic enthusiasm epitomised by the hundreds of millions of additional prescriptions every year did not carry a substantial cost: the financial cost to the Treasury (or individual); the opportunistic cost to the Health Service, where the increase in the nation's drug bill over the last ten years is equivalent to employing an extra 15,000 nurses; and the considerable cost to the public in the perils and discomforts of the (inevitable) side-effects that come from taking so many pills. These ‘costs' could be elaborated on with numerous illustrative examples – as the shelf-ful of books cited earlier would suggest. Here just two examples must suffice – the extraordinary phenomenon that is the antidepressant Prozac (and its many imitators) and the near universal prescription of the cholesterol-lowering statins.

Prozac needs no introduction, being one of the handful of drugs – along with Valium, Viagra and ‘the Pill' – whose cultural significance transcends their pharmacological properties. Nonetheless, its phenomenal success poses something of a paradox given ‘the Revolution in Psychiatry' of the 1950s (as described in Chapter 4 of the Prologue) with the discovery in
a very short period of drugs for the full range of mental illness – psychosis, anxiety, depression, mania, and two types of antidepressants of undoubted efficacy, widely prescribed. Then came Prozac, the first of the SSRIs (selective serotonin reuptake inhibitors), so called because of their ability to increase the level of the neurotransmitter serotonin in the brain, launched in 1989 with the dual advantage of being both easy to take (just a single pill a day) and better tolerated than its predecessors. Prozac rapidly displaced the earlier anti-depressant drugs such as amitriptylene, and within a few years doctors in Britain were writing 14 million prescriptions annually. But it did not stop there. The number of prescriptions continued to rise. By 2003 it had climbed to 27 million. By 2008, 36 million. These prescriptions are usually issued monthly, which would mean that over the last twenty years the numbers taking one or other of these ‘happy pills' had increased from 1 to around 3 million. The same pattern, replicated in countries around the world, turned Prozac and its imitators into ‘blockbusters', generating combined sales of around $19 billion – far in excess of the earlier antidepressants that they had displaced.

The most reassuring of the possible explanations is that this represented a ‘catch-up' phenomenon, where the superiority of Prozac over earlier types of antidepressant encouraged doctors to prescribe them more widely to those whose depression in the past might have gone untreated. They were further encouraged to do so by an officially sanctioned change in the classification of depression, considerably widening the scope for those who might benefit from this class of drugs. Prior to 1980 psychiatrists distinguished between ‘melancholia', a severe, protracted, often lifelong – if fluctuating – gloominess of spirit, and the much commoner ‘reactive depression', with similar but less severe symptoms, usually brought on in reaction to an adverse life
event – unemployment, marital breakdown, bereavement and so on. This reactive depression clearly warranted support and sympathy, with the general expectation that it would resolve in time without the need for any specific medication. But then the American Psychiatric Association, during one of its periodic revisions of the diagnostic criteria of mental illness, abolished the distinction between ‘melancholia' and ‘reactive' depression in favour of conceiving of depression as a continuum from ‘major' to ‘minor' – with ‘minor' being defined as a dysphoric mood lasting for more than a fortnight with sleep disturbance, loss of appetite, fatigue, crying and ‘feeling sorry for oneself'. These symptoms are so common that virtually anybody could be diagnosed as suffering from depression warranting medical treatment at some stage or other of their lives.
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The covert ‘branding' of psychological traits as psychiatric illnesses (shyness as social phobia), as outlined above, was a further contributory factor, as psychiatrist William Appleton describes): ‘Those with eating, sexual and posttraumatic stress disorders [became] candidates for Prozac . . . and the timid, those with low energy and low self esteem, those who are irritable, or perfectionists, or suffering from a general malaise or unhappiness; in short, anyone – sick or not – may benefit from the civilizing effects of Prozac.'
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The proposition that so wide a spectrum of psychological disturbances might be treatable with the same drug captures the brilliance of the two-pronged marketing strategy that lay behind Prozac's success. This entailed narrowing the wide range of mental afflictions to a single cause – that they are all due to the same disturbance of brain chemistry, a deficit of the neurotransmitter serotonin – and simultaneously expanding the numbers of those who might benefit from having that deficit corrected by taking Prozac or its equivalent. Thus a widely
publicised and seemingly authoritative survey in the 1990s claimed that about one in three adults in the US was suffering from mental illness warranting treatment.
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The message for family doctors attending industry-sponsored meetings and symposia could not have been simpler – the problem of mental illness is much more prevalent than previously supposed and they would be doing their patients a favour by identifying those who might benefit from being on medication.

There were dissenters, of course. ‘Many of those with depression are not depressed at all,' observed Alastair Santhouse, consultant in psychological medicine at London's Guy's Hospital, writing in the
British Medical Journal
: ‘more detailed questioning reveals a familiar pattern in which the patient lacks a sense of purpose in life with no goals or aspirations.'
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And while no doubt many are grateful to Prozac for helping them through an emotional crisis in their lives, it is almost absurd to suppose that so wide a range of mental states can have a single cause – or indeed that it is possible to prescribe brain-altering chemicals to people without running into trouble. And here two problems in particular have emerged in the last decade: they can induce a severe ‘withdrawal syndrome', and increase (paradoxically) the risk of suicide, especially in adolescents.

The massive popularity of Prozac (and its several equivalents) is predicated on the assumption that they can be taken for six to nine months during an episode of depression and then discontinued safely. For some this may result in a resurgence of psychological symptoms, usually attributed to a resurgence of their previous depressive illness indicating the need to continue taking their medication. This sounds plausible, except that there are those for whom it clearly does not apply, as no matter how long they have been on medication they find it very difficult to ‘come off'. This graphic account of a woman trying to ‘come
off' the antidepressant Seroxat after five years is strongly suggestive of some form of withdrawal syndrome: ‘I was in physical and emotional turmoil. The nausea returned along with flu-feelings, aches, blinding dizziness, exhaustion, rapid and painful successive electric shocks . . . Most disturbing was the onset of suicidal thoughts and violent nightmares in which I saw members of my family hurt. For weeks I was unable to leave my bed.'
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The manufacturers, GlaxoSmithKline, always insisted that this type of withdrawal syndrome was extremely rare, pointing to the findings of clinical trials which showed an incidence of about 1 in 500. Subsequently, in response to much adverse publicity, they were obliged to acknowledge this underestimated its frequency 125-fold and this withdrawal syndrome actually affected one in four of those taking the drug.
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Next there is the powerful impression of parents whose children tragically take their own lives soon after starting anti-depressant medication that it might have exacerbated their emotional distress. This, for obvious reasons, is almost impossible to prove for any individual case, but when the regulatory authorities investigated this matter further it emerged that previously unpublished findings from clinical trials confirmed a small increased chance of suicidal thoughts – prompting them to withdraw approval for their use in adolescents, other than in the most severe cases.
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These cautionary lessons illuminate how the phenomenal success of Prozac and similar drugs concealed the sheer implausibility of supposing that all manner of mental problems – from minor to major, in teenagers and in adults – could warrant the same treatment. And, further, how readily the findings of clinical trials can be creatively presented to conceal the harmful consequences of such a proposition.

But for all that, there is no disputing that for the vast majority Prozac is highly effective – or is it? In 2007 psychologist Irving Kirsch invoked the Freedom of Information Act in the United States to compel the pharmaceutical companies and the drug regulatory authorities to release the data of all the trials conducted. This predictably revealed a series of dodgy practices – withholding the results of those trials that failed to produce the correct answer, together with the self-explanatory practices of ‘salami slicing' and ‘cherry picking'. ‘My colleagues were led to the inescapable conclusion that these are no more than active placebos with very little therapeutic benefit.'
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There are of course counter-arguments, of which the commonest is to acknowledge that the scientific evidence of all those clinical trials may indeed be flawed and biased but to admit nonetheless that ‘everyone knows they work in clinical practice'. And some of those with depression are indeed highly sensitive to these drugs in ways that would support the hypothesis that depression is primarily due to a chemical imbalance of serotonin in the brain. But the substantial point remains that the Prozac saga illustrates the powerful influence of Big Pharma in persuading psychiatrists and doctors into supposing they understand much more about the workings of the mind than they really do, and that whatever is amiss can be readily fixed.

It will be recalled how, following the protracted effort to implicate ‘high fat' meat and dairy foods as the main cause of the epidemic of heart disease (as described in ‘Seduced by the Social Theory'), the drug companies had ‘snatched victory from the jaws of defeat'. Certainly, the effort to encourage tens of
thousands of people, in the largest and most costly trials in the history of medicine, to adopt a ‘healthy' diet had zero effect in reducing their subsequent chances of a heart attack. But the central principle endured, that raised cholesterol levels in the blood predisposed to heart disease which could be prevented by taking potent cholesterol-lowering medicines such as cholestyramine. This led to the notion of ‘the lower the cholesterol the better', where millions of people whose cholesterol level was just ‘above the average' would also benefit from having it lowered. But this would require a drug that, like Prozac, was easy to take and with a ‘favourable side-effect profile'.

That drug was lovastatin, the first of the statins, introduced in 1987, prompting the medical experts of the day involved in the National Cholesterol Educational Programme to advise that everyone should ‘know their number' – visit their doctor to have their cholesterol level determined and, where appropriate, take medication for life to lower it.

By the mid-1990s lovastatin, together with the several ‘me-too' variations of its competitors, was generating revenues of $3 billion a year. Fifteen years later that had mushroomed to $26 billion – making statins by far the single most profitable class of drugs ever discovered. Thus the rhetoric of the Social Theory, that people could ‘take control' of their health by their own efforts and thus avoid having to take drugs or undergo bypass surgery for heart disease, had transmuted into its antithesis, where vast numbers who were otherwise healthy were now committed to taking potent drugs indefinitely.

Big Pharma may have turned the ‘cholesterol consciousness' generated by the diet-heart thesis to its advantage, but two further factors would drive the ascendancy of the statins. First, several drug companies, recognising the bounteous potential of lovastatin, promptly came up with half a dozen sequels and, in
the subsequent scramble to secure a share of the market, ingeniously transformed the clinical trials necessary to demonstrate their efficacy into a marketing strategy. The trials were given catchy names such as Excel, Prosper and Care and organised on a massive scale involving up to 10,000 patients recruited from many different academic centres. This had the advantage of encouraging brand loyalty, where cardiologists, generously rewarded for participating in one or other of the trials, might reasonably be expected to carry on prescribing them – and encourage others to do likewise.
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The cumulative effect, with the favourable results of the trials being announced with great razzmatazz at medical conferences attended by tens of thousands of specialists, generated an almost evangelical enthusiasm for the statin project. And as time passed the more impressive, strikingly so, the findings of these trials proved to be: by 2004 the Heart Protection Study had ‘overturned conventional wisdom' to demonstrate that statins worked for everyone – young and old alike, men and women, those with normal and raised cholesterol and so on. These findings, claimed Professor Rory Collins of Oxford University, suggested that tripling the numbers of those taking statins in Britain from 1 to 3 million would save 10,000 lives a year.
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The further, yet more influential factor in the propagation of the doctrine of salvation through statins would be the drive to establish ‘clinical practice guidelines' where panels of ‘experts' deliberate together to determine the optimal treatment for any condition. The guidelines then become ‘official policy', with the possibility of financial penalties for doctors who fail to adhere to them. Here the question, on which the fortunes of the statin class of drugs turned, was whether their value in those with high cholesterol levels could be extended
to the vastly greater numbers of those whose cholesterol was above ‘normal' – and the cut-off point for initiating treatment.