Joan-Ramon Laporte is one of the most important figures of pharmacology in Europe. In 2016, the review Pharmacoepidemiology and Drug Safety requested him an opinion article at the occasion of the 50 years of the event that is considered the starting point of pharmacovigilance in the world, the thalidomide disaster and the subsequent actions implemented by the governments for the surveillance of the safety of medicines.
In this article, Laporte outlined the hypotheses that, in a less technical way, he exposes in his book Chronicle of an intoxicated society. Namely, that the intensive and extensive use of medicines (with higher than necessary doses, for longer than necessary, for indications other than those where efficacy has allegedly been demonstrated) is one of the main causes of disease, disability, and death in the world.
This bleak conclusion is a gigantic social failure, which may have been especially difficult to recognize for an academic and scientific who has dedicated his life to study, investigate, teach and boost pharmacology and pharmacovigilance.
Laporte raises the text as a work hypothesis. Starting from scientific data, the author intends, above all, to generate reflection for action:
“The inadequate and excessive consumption of drugs is a problem of global dimensions, which requires scientific, ethical, medical, political, and legislative action, at local, national, and international levevl. Health, health care and medicines are collective goods. As such they must be subject to public debate. This book aims to provide elements of reflection from the perspective of a clinical pharmacologist. Surely they can be very enriched by the contributions of other pharmacologists, other health professionals, patients, epidemiologists, historians and philosophers of science, psychologists, jurists, activists, sociologists, economists, and perhaps some politician.”
Laporte’s starting point is perplexity, the first intellectual action of every good scientist. He is, above all, a scientist who maintains his ability to become perplex and defending that the most important mission of science is producing knowledge for improving our lives. This is what his book pretends.
In the first 10 chapters Laporte explains what medicines are, and how they have been discovered and investigated. He examines the concept of «magic bullet», a term created by Paul Ehrlich, the discoverer of the typhoid toxin and of the first drug used for the treatment of syphilis at the beginning of the 20th century. By this concept, every disease would end up having its specific therapy, with specific molecules that would cure diseases by addressing their basic etiology, without affecting the rest of the body. This myth has inspired pharmacological research since then:
“A magic bullet is perfect to cure a disease and has no adverse effects. It acts selectively on a biochemical receptor, repairs its function, and thus relieves the symptoms of the disease, it can even cure it. Unfortunately, only antibiotics, vitamins and insulin and other hormones approach the concept of magic bullet, but they are rather exceptions, and as magic bullets they are imperfect.”
The problem is that this myth –very rarely a reality, as myths are– is still invoked as a powerful advertising slogan, a fiction technology totem with an enormous capacity to generate societal overvaluation and, what is worse, overevaluation by professionals responsible for their use:
“In our society the Magic Bullet model is often invoked, implicitly or explicitly, to describe the alleged or expected effectiveness of drugs, vaccines and other medical interventions. Expressions such as «new therapeutic targets», «selective action», «molecular level» and others are turned into the slogans of marketing materials. It is a convincing rhetoric. Very often in medicine ignorance appears disguised with a magic and arcane language, the patina that medical culture needs to be convinced that it is facing a true innovation.»
Laporte quotes a study showing antibiotic properties of hundreds of non-antibiotic drugs (including omeprazol, and some neuroleptics, benzodiazepines, anti-inflammatory agents and many others). The simplifying fantasy of the existence of an alleged precision pharmacology contrasts with the reality that Laporte calls «therapeutic in shotgun pellet»:
“In a strict sense, there is no medication that is a magic bullet. A few interventions approach it, but not many. With greater or lesser intensity, the drugs interact with multiple receptors, apart from the one presented as unique and specific. Each of these receptors is part of a complex biochemical or physiological pathway in which many other receptors are involved. In addition, each receptor contributes to the operation of several pathways. The result is that each drug produces a wide variety of physiological effects, which also have a waterfall effect on other ways. The condition of specificity, therefore, cannot be satisfied.»
The vast majority of the most consumed medications are currently far from being «magic bullets» although they are sold as such. What is worse, they are too often used as if they were.
The myth of the specificity of the magic bullet is linked to an oversimplification of the biological mechanisms of disease, which is particularly worrying with regard to mental and chronic diseases, with disregard of the social context (patient, family, community) where medicines are used. These founding myths of pharmacology are tremendously important for Laporte:
“The magic bullet drug model that has to get there and there practices a precise repair is an idealization. However, this metaphor has guided much of pharmacological research in the last 100 years, and is used abusively for the cultural and commercial promotion of medicines, because it is appealings. Although it is reductionist, it sounds simple. It is easy to explain with short messages and advertisements. It is a powerful financial incentive, because magic bullets can be produced on a large scale and are easy to distribute and sell, if compared to social and economic interventions or with modifying living habits, which are not patentable, nor easy to produce, distribute and sell.»
However, medicines utilization is a social phenomenon where uncertainty is not only biological. Unfortunately, the lack of reliability of scientific studies supporting the benefits of their use adds to this uncertainty. Four decades ago, the neoliberal revolution inpired by Thacher and Reagan led to research, especially the clinic, was funded by private companies. Leaving exclusively in the hands of companies the generation of the data on the efficacy and safety of new medicines does not seem a very intelligent idea. Healthcare systems take for granted the results of clinical research done by companies, without any testing of its effectiveness and safety in routine practice.
Laporte explains the power of the placebo in a very enjoyable way and how companies use it skillfully –together with the manipulation of the scientific method used to justify the effectiveness of medicines, the clinical trial– to almost always obtain the desired results.
This serious process of systematic betrayal of the spirit of science is reinforced by the capture that pharmaceutical companies have made of the entire chain of medical knowledge, not only of clinical research, but also of its publication, dissemination, synthesis, teaching and prescribing.
Despite these concepts may seem very technical, the book is very enjoyable because the author chooses commonly used medicines to illustrate both research processes and the consequences of their overvaluation through the complex marketing strategies of the industry.
The central chapters of the book, perhaps those which have aroused more interest and controversy, are those specifically devoted to its title:
“In 2022 in Spain, 1,100 million medicines prescriptions were made in the public health care system (23 recipes per inhabitant). To this figure we should add about 270 million units dispensed in pharmacies without a medical prescription and medicines prescribed in hospitals. Prescription drugs with the highest consumption were analgesics (131 million units), followed by antihypertensive drugs (102 million), cholesterol-lowering agents (82 million), anxiolytics and hypnotics (77 million ), omeprazol and analogues (74 million), and antidepressants (53 million). Of every 10 citizens, three take some psychotropic, three omeprazol or an analogue, and two a cholesterol-lowering agent.”
The data are overwhelming due to their dimension, especially among the elderly. For example, for psychotropics:
“Of every two people over 70 years old, one (usually a woman) receives a psychotropic drug at least once a year. In this age range, one in four people take a drug for depression, one in four a sleeping pill, and one in ten a neuroleptic. Many consume two or three psychotropic drugs concomitantly.”
The effectiveness of most psychotropic drugs is debatable, but their excessive use is obvious (it seems impossible that half of the elderly need medications for mental alterations) and their risks, particularly in the elderly:
“Psychotropic drugs cause problems of attention and memory and difficulty in making decisions…, with their continued consumption high concentrations accumulate in the nervous system. Many people in these situations impressively improve if this medication is gradually withdrawn.”
«Many doctors,» says the author, «consider it as a kind of mental doping: they think they help the elderly and lonely people with these medications, but actually they poison them.»
Currently, almost 10% of the population in Spain consume five or more different drugs in a concomitant and continuous way. Half of those over 70 take five medications or more. Of every 100 people over 65 years-old, 30 take six or more medicines concomitantly (with wide variability between autonomous communities, from 15 in the Basque Country to 40 in Murcia).
Polymedication is a risk factor by itself:
“When several drugs are taken at the same time, interactions can occur between them, that is, a drug can modify the effect of another: by increasing it, with possible toxicity, or by decreasing it, with loss of its effectiveness. The problem is that the interactions between drugs are studied by peers: they have generally been evaluated in healthy and young volunteers, if the drug a modifies the effects of drug B, and vice versa. Very rarely the interactions between three drugs are studied. There are no studies in which the interactions between four medications taken concomitantly have been evaluated. A person who takes more than four drugs is much more likely to suffer some of its adverse effects than the sum of probabilities of each drug separately.”
A large number of these medications simply lack any demonstrated efficacy (mucolytics, antispasmodics, medications for dementia or osteoarthritis, drugs for venous varicose veins, cerebral vasodilators , etc.). A large proportion have been inadequately prescribed, because they are not indicated or because they are left more time than necessary. For example:
“in Catalonia every year statins are prescribed to almost one million people, but only about 150,000 may obtain a beneficial effect, according to the results of clinical trials, therefore leaving 850,000 people who do not take any clinical benefit from their consumption but are exposed to muscle or joint pain, diabetes or hepatitis, among other complications”
The consequences are serious. For example, Laporte infers from epidemiological studies, that in Spain, «there could be between half a million and eight hundred thousand hospitalizations caused by adverse drug effects» every year, that is, between 13 and 16% of all hospital stays.
The balance is terrifying:
“In Catalonia every year the adverse effects of medicines cause at least 100,000 hospitalizations, some thousands of deaths inside and outside hospitals, 3,000 cases of serious hemorrhage, more than 2,400 of hip fracture, several hundreds of pneumoniA, tens or hundreds of cancers, several hundred cases of atrial fibrillation, hundreds of cases of diabetes, thousands of people with sexual dysfunction, thousands with muscle aches, an indeterminate number of episodes of violence and aggression, myocardial infarction, false diagnoses of dementia, of suicides…».
If these numbers are multiplied by six or seven, approximate figures may be estimated for Spain. Dr. Laporte states:
«If 50 years ago the main challenge of health systems was to guarantee universal access to healthcare, at present, in rich countries, its main therapeutic challenge is to withdraw unnecessary medication to people.»
Rather than regress, the problem of medicines misuse will increase:
“Drug utilization patterns deny that the practice of medicine is based on the best evidence: the prescription of useless drugs and of medications with cosmetic effects on laboratory tests is more than prevalent. Unjustified polymedication grows, spurred by the recommendations, clinical practice guidelines, and protocols inspired by an evidence-based medicine which assumes us all the same and uniforms and which is in turn based on industry-inspired trials.”
Professor Laporte recommends a series of safeguarding questions that every patient should do to his doctor before any prescription:
«What is the goal of the treatment (A goal which is important for the doctor may not be important for you). Have you checked that the dose you are prescribing is adequate for me? Would it be wiser to start with a lower dose and see how it is going? (Some doctors tend to prescribe the same dose to a 45 kg person than at one of 85. Ask if the dose is suitable for your weight). Is the medication you are prescribing compatible with all other medicines I am already taking? Can’t one medicine cancel the effect of another one? Or, on the contrary can it exaggerate its effects? For how long is the treatment scheduled? And if you can’t tell me, when will we be in contact to evaluate how it works and to decide if I continue with this drug?”
Overprescribing of medicines is not only a public health problem. It has also to do with the sustainability of the healthcare system:
“According to data from the Ministry of Health, in 2021 the total public healthcare expenditure was 87,941 million euro. The medication spending was 20,939 million (12,809 in medications dispensed in pharmacies and 8,408 in hospitals). Therefore, in Spain pharmaceutical expenditure accounted for 25.7% of total healthcare expenditure.”
This rate is more than two-fold the rate in Denmark, Sweden or The Netherlands (between 10 and 11%), where healthcare is certainly not worse than ours.
A complex problem, therefore, that requires complex solutions. The last chapter of the book describes some key elements and potential solutions:
- Too much offer,
- System intelligence in the hands of the industry,
- Poor management,
- Patient overvaluation,
- Poor working conditions of professionals,
- Conflicts of interest,
- Lack of a public health-oriented pharmaceutical policy.
Laporte is clear:
“A more cautious use (less drugs, lower doses of some of them) and more adjusted to the individual needs of each patient and to the social context would also contribute to avoid the disease, disability and death caused by medicines, as well as the cost that this involves for our health system, which is the main responsible institution for promoting a healthy use of medicines. If the health systems selected the medicines they need and they avoid those which are useless and superfluous, many adverse drug effects (ADE ) would be avoided. If they had mechanisms aimed at verifying the efficacy and safety of the drugs that select, for example, through the intensive surveillance of the first 1,000 or 10,000 treated patients, and if they decided accordingly, many unnecessary ADE would be avoided. If they were constituted as a permanent and critical observatory of the prescription and consumption patterns of medicines, many ADE would be avoided. If prescribers received information and training not supplied by pharmaceutical companies or their messengers, many unnecessary ADE would be avoided. If conflicts of interest with pharmaceutical companies among professionals and managers of health systems were avoided, many ADE would be avoided. In addition, these actions and others would help optimize the necessary treatments, and multiply their effectiveness. I do not see other ways to avoid the paradox that the health system becomes one of the main causes of illness –if it is not already it.”
We have a serious problem that is not just a matter of better science or more control by the administration. In its origin, it is a cultural problem. In my opinion, it is a kind of socially desired technological response to the universal fear of death:
«For the whole healthcare system and for society, the consumption of drugs symbolizes the desire and the ability to modify the «natural» course of diseases. Fears and uncertainties encourage magic thinking. Medications and vaccines are a symbol of hope in the face of fear and uncertainty. They are often subject to rites of false prevention or false treatment of non-existent or infrequent problems. More generally, they are subject to the ritual of blind trust in progress and science. But beyond its beneficial and adverse effects, the consumption of medicines is a cultural characteristic: it is a reflection of the hopes that society entrusts to the ability of medicine to preserve health and to cure or relieve the disease, and in a more general way it is also a reflection of what each society understands as health and disease.”
This book is ultimately necessary and rigorous, but also entertaining and healthy. Healthy because it can contribute to change the relationship between patients and their medications, so that they have a more balanced vision of their usefulness. Written by a scientist and academic who has dedicated his entire life to the study of medicines, who therefore loves pharmacology, it has special relevance as a testimony that is still that of a failure. Abuse and misuse of medicines in our health system is not something irremediable. Read Professor Joan Ramon Laporte.
It is one of those few signs of hope that we still have.
Abel Novoa is a family doctor and president of the Association for the Defense of Public Health of the Region of Murcia