Big Pharma and the Death of Americans

This article is related to Anthony Biglan’s new book Rebooting Capitalism: Forging a Society that Works For Everyone.

When asked who owned the patent of the vaccine, Salk famously remarked, “There is no patent. Could you patent the sun?” Talk about selfless service to society!1

Of all the industries I am covering, the pharmaceutical industry might lay claim to being the industry with the largest net benefit to humans. Start with antibiotics. My older sister, Hekate, tells me that when I was an infant in 1945, I was hospitalized for pneumonia, and they feared I would die. My uncle Al, however, was a physician who was in the military. He was able to get the new wonder drug, penicillin. It may have saved my life.

Since the discovery of antibiotics, millions of lives have been saved. How many? I find claims that penicillin alone saved between eighty and two hundred million lives, but I cannot find any actual data. We do know that penicillin was the first drug that effectively treated pneumonia, strep throat, scarlet fever, diphtheria, syphilis, gonorrhea, meningitis, tonsillitis, and rheumatic fever.2 Certainly penicillin and the other antibiotics developed since then have made a huge difference in human wellbeing.3

Very significant progress has also been made in pharmaceutical treatments for cardiovascular disease. For example, a meta-analysis to assess the average impact of statins across multiple experimental evaluations of them showed that they lowered the risk of death by 19%.4 Similarly, a meta-analysis of evaluations of anti-hypertensive medications showed that they lower the rate of any cardiac event by 22% and the rate of strokes by 41%.5

In sum, there is no question that the pharmaceutical industry has been of great benefit to human wellbeing. However, the industry has also evolved some harmful practices. I review several of them and describe how they evolved. As you will see, this is another example of an evolutionary process that was driven by the profits they produced for the industry.

Harmful Consequences of Some Industry Practices

I will only present four examples of harmful practices, but they suffice to show how even an industry that is organized to produce much better health of American’s can evolve practices that reduce wellbeing.

The Opioid Epidemic

The number of people killed by opioid deaths is stunning. The Centers for Disease Control reports that between 1999 and 2016, more than 630,000 people died from a drug overdose involving prescription opioids or heroin.6 A New York Times investigation concluded that more than 59,000 people died of some form of drug overdose in 2016. That would make it the eighth leading cause of death.7

There are a number of reasons for this epidemic, including the loss of jobs among working class people and the instability of families, which I document in Rebooting Capitalism. However, a major cause was the shift toward aggressive treatment of pain with opioids. In testifying at a Senate Caucus on International Narcotics Control,8 Nora Volkow, the Director of the National Institute on Drug Abuse cited three factors leading to the opioid epidemic: “drastic increases in the number of prescriptions written and dispensed, greater social acceptability for using medications for different purposes, and aggressive marketing by pharmaceutical companies.” She indicated that 76 million prescriptions for opioid pain killers were written in 1991, but by 2013, the rate had risen to nearly 207 million, which is two thirds of the U.S. population.

A thorough and I think balanced account of the history of the opioid epidemic was written by Chris Elkins. It can be found at the website of DrugRehab.com (https://www.drugrehab.com/opioid-epidemic/). He recounts how the U.S. has gone through several different periods of widespread use of opioids and other periods where their use was very limited. In the late 19th century opioid addiction was common. The extensive use of morphine during the Civil War contributed to high levels of addiction. Morphine was available without prescription at that time. In 1914, however, the Harrison Narcotics Act made opioids available only by prescription. What commenced was a period where physicians avoided prescribing them even for people who were dying of painful cancers.

In the 1980s, however, thinking about pain relief began to change. There was a report that people treated in hospitals with opioids seldom became addicted. Another concluded that for non-cancer pain patients, these medications could be safely prescribed with little risk of abuse. That study called for further research to assess long-term outcomes, but those studies were never done.9

In the 1990s, given the reports of the apparent safety of opioids and the increasing advocacy for better pain relief, the three pharmaceutical companies that made these narcotics– Purdue Pharma, Johnson & Johnson, and Endo Pharmaceuticals—began to aggressively market them for long-term use with patients with non-cancer related pain. The companies funded the creation of American Academy of Pain Management and the American Pain Society, the latter of which developed guidelines which advocated expanded use of these medications. The companies provided continuing education to physicians which encouraged prescribing these medications for pain.

Not only was there an effort to promote the prescription of these narcotics, there was a move to punish physicians for failure to adequately treat pain. Physicians with ties to the drug industry drafted rules that the Federation of State Medical Boards adopted, calling on state boards to punish physicians who failed to prescribe medication for pain. The Federation was at that time receiving funds from the drug companies.9

The dramatic rise in overdoses from opioids led to efforts to curtail prescribing. Wilson Compton and his colleagues10 reported that the rate of prescribing and the rate of overdose deaths due to opioids plateaued in states that were working to reduce the over-prescription of opioids. However, with millions of Americans addicted, it is not surprising that, as it became harder to get them, some turned to heroin. Compton et al. report that “914,000 people reported heroin use in 2014, a 145% increase since 2007” and that “mortality due to heroin overdose more than quintupled” between 2000 and 2014. They indicate that people who are already addicted to prescription opioids are particularly likely to begin to use heroin. They attribute the increasing use of heroin to the fact that it has become cheaper. It seems that the drug cartels are outselling the pharmaceutical companies.

The Treatment of Attention Deficit Hyperactivity Disorder (ADHD)

The U.S. has a higher rate of diagnosing and medicating ADHD than other countries. They are ten times greater in the United States than in the United Kingdom.11 There was a five-fold increase in the number of U.S. children being medicated with psychostimulants between the period 1988-1994 and 2007–2010.12 Young children (under age 5) are increasingly being medicated. The CDC raised concerns about overmedication of young children with psychostimulants; 75% of young children who have a diagnosis of ADHD are on medication, generally either Adderall and Ritalin.13 This is true despite the fact that the American Academy of Pediatrics recommends the use of behavior therapy rather than medication for young children who “have” ADHD. They point out that behavior therapy is effective and that the impact of given young children psychostimulants such as Adderall and Ritalin is unknown and could be harmful.

Sanford Newmark, the head of the pediatric integrative neurodevelopmental program at the University of California, San Francisco, says that the long-term effects of these drugs have not been well-studied. Side effects of these medications include poor appetite, sleeplessness, irritability and slowed growth.14

Research beginning in the 1970s showed that stimulant medication of children can impede their growth.15 However, additional studies have not replicated this effect.16

Although concerns have been raised that these medications could lead to drug abuse in adolescence, the research indicates that use of these medications is associated with a lower likelihood of drug abuse in adolescence and early adulthood.17

Despite evidence of the value of behavior therapy18 and omega 3 fatty acid supplements,19 for the treatment of ADHD, the dominant treatment for ADHD continues to be psychostimulants. The main reason seems to be that none of the alternative treatments are being promoted with anything like the skill and budget that the drug makers are spending on marketing and promotion.

Unlike most physical disorders—pneumonia, cancer, heart disease–there are not clear cut physiological processes that can be used to diagnose ADHD. ADHD is a behavioral disorder. If you look at the behaviors that are said to be diagnostic of ADHD, you can see why it has been easy to promote the prescribing of psycho-stimulants to young children. According to DSM 5 a child can be diagnosed as “having” ADHD if they are inattentive and/or hyperactive. Examples of inattention include:

  • Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
  • Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations, or lengthy reading).
  • Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction).
  • Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked).

If you have or have ever had a young child, it would be remarkable if you had not observed these behaviors.

Examples of the behaviors that count as symptoms of hyperactivity or impulsivity include:

  • Often fidgets with or taps hands or feet or squirms in seat.
  • Often leaves seat in situations when remaining seated is expected.
  • Often unable to play or engage in leisure activities quietly.
  • Is often “on the go,” acting as if “driven by a motor”.
  • Often talks excessively.
  • Often blurts out an answer before a question has been completed.

These are the behaviors that young children engage in. It should not be surprising that the youngest children in any given grade are more likely to be diagnosed as “having” ADHD and be put on medication.20. If you were a parent of a child who engaged in these behaviors “often” (how often is often?) and you believed that ADHD is a physiological condition, and you were highly motivated to be sure your child was treated for any illnesses they had, and you had been exposed to pharmaceutical advertising of ADHD medications, how likely would you be to allow your child to be put on medication if they exhibited many of these behaviors?

My reading of the research on the effects of psychostimulants does not lead me to conclude that the harm of these medications is proven. But their safety for young children has also not been proven. And, it is clear that the extensive prescribing of these medications is more a function of the marketing skill of the pharmaceutical industry than the harm to public health of hyperactive children.

I can remember sitting next to my son in a movie theater and being driven crazy by his constant movement. Sleeping with him was an adventure. Yet as a person familiar with behavior therapy and aware that the risk of hyperactivity for further problem development had only been found for children who were also aggressive,21 there is no way that I would have had him medicated. (He turned forty this year; he is a successful business man and a wonderful human being—and he does not fidget anymore.)

The Evolution of Resistant Strains of Bacteria

My mother was a nurse at the University of Rochester’s Strong Memorial Hospital in the early 1960s. At that time, there was a dramatic rise in a strain of staphylococcus aureus in hospitals that came to be called “hospital staph.” Patients admitted to the hospital often contracted the infection. Many died.

My mother was a good manager. They had put her in charge of the hospital ward for burn patients. One of the greatest dangers to the survival of burn patients is infection. My mother implemented a system for the ward, which involved sterile precautions for the treatment of burn patients. Whenever a staff member went into a patient’s room, they donned a protective gown, put on a mask so that the patient would be exposed to as few germs as possible. And so when the staph infections became a serious problem, they put those patients on my mother’s ward, because her staff were trained in sterile precautions. (The rooms were all singles and they were thoroughly fumigated after every patient.)

This was an early harbinger of what was to come. The principles of variation and selection are at the root of this story. If you have ever taken antibiotics, you know that your instructions were to take the entire course of antibiotics, even if your symptoms disappeared before you finished taking them. This is important because the germs the antibiotic is going after vary in how readily the antibiotic will kill them. In the first few days of taking the drug, the least-resistant bacteria are done in. When that happens, your symptoms may disappear. But if you stop taking the antibiotic then, the more resistant bacteria will remain and you will have selected that more resistant strain. Those remaining bacteria may multiply and may prove very difficult to kill.

I think what happened in hospitals is that whenever a patient got a staph infection, they used penicillin to treat it. I suspect they also got more lax about sterile precautions, because everyone knew they now had the miracle drug. As a result they selected this very resistant strain.

The problem of antibiotic resistant bacteria has grown. A report of the CDC in 201613 showed that about two million Americans are infected with antibiotic resistant bacteria each year and about 23,000 die as a result.

A study published in the Journal of the American Medical Association (JAMA) by the Centers for Disease Control and Prevention (CDC) concluded that about 30% of the antibiotics prescribed in the United States are unnecessary.13,22 The most common misuse is the prescription of antibiotics to treat virus infections of the respiratory system. Antibiotics simply don’t kill viruses. But their use in this way is contributing to the selection of resistant bacteria.

Another factor that contributes to the problem is the extensive use of antibiotics with livestock. They are used in three ways: (a) to treat infected livestock; (b) to prevent livestock from becoming infected; and (c) to accelerate their growth. Melinda Moyer, writing in Scientific American, describes visiting a 40 by 200 foot barn that held eleven hundred pigs. Having them in such close quarters is one reason that antibiotics are needed. In addition to the concern that these practices may be contributing to bacterial resistance, there is a concern that the antibiotics will remain in the livestock when they are consumed by humans.23

Recent research shows that resistance can spread more rapidly than was believed. Research in the Netherlands has shown that a resistant strain of Staphylococcus Aureus was being passed from pigs to humans.24 Moyer argued that: “In 2014 pharmaceutical companies sold nearly 21 million pounds of medically important antibiotics for use in food animals, more than three times the amount sold for use in people. Stripped of the power of protective drugs, today’s pedestrian health nuisances—ear infections, cuts, bronchitis—will become tomorrow’s potential death sentences.”

A third reason for the rise of antibiotic resistance is the manufacturing process for these drugs. An investigative report by SumofUs.org, a non-profit organizations working to “stop big corporations from behaving badly,” reported that the release of antibiotics into the environment through polluting practices of drug manufactures, careless disposal of antibiotics, and human and animal excretion of them have been overlooked as a source of bacteria resistance.

In order to control the uses of antibiotics with livestock, the Food and Drug Administration implemented regulations in January of 2017 requiring a prescription from a veterinarian. However, the pharmaceutical industry has expanded its marketing of antibiotics for animal use around the world, in places where regulations are lacking.25,26

The Rise of Anti-Depressive Medication

Twelve percent of American adults (29 million people) are taking anti-depressive medication.27 And according to the Director of the National Institute of Mental Health, 80% of these prescriptions are not written by psychiatrists and an unknown number of them are written for people who are not diagnosed as depressed.28

Irving Kirsch from the UK and five researchers from the U.S. did a meta-analysis of the results of all of the randomized trials that were submitted to the U.S. Food and Drug Administration to get approval for these drugs. The meta-analysis provides a statistical summary of the results across studies. They found that these anti-depressives had significant benefit only for people who were severely depressed.29 Moreover, they concluded that the reason that these trials show better outcomes for the severely depressed than for less depressed patients is not because the anti-depressive medication is more effective for severely depressed patients, but because the placebos do not have as much effect for these patients. In addition, it should be noted that two thirds of the people in these studies were not severely depressed. In other words, two thirds of the people prescribed these medications may be getting no benefit at all.

There is a risk of suicide and aggression in the treatment of children and adolescents with anti-depressive medication. The Nordic Cochrane Centre analyzed evidence regarding suicide and depression during anti-depressive drug therapy involving selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).30 They obtained the reports that the drug companies had submitted to the UK and the European authorities to obtain permission to prescribe these drugs. However, they reported that much of the information regarding possible harm to patients was missing from the reports. Nonetheless they found that the children and adolescents in these trials had more than double the rates of aggressive and suicidal behavior compared to those receiving placebos.

The brain hypothesis. A widely accepted theory of how anti-depressive medications work is that depression is due to low levels of serotonin in the brain. Serotonin is a neurotransmitter that is involved in the way that neurons stimulate other neurons. The first neuron releases serotonin. When the serotonin fills the space between neurons, it stimulates the next neuron to fire.

It is on the basis of this theory that depression has been considered to be due to a deficit in serotonin. The evidence has not supported this theory. People who are depressed do not have reliably lower levels of serotonin. Here is a summary of the evidence from a paper published by Lacasse and Leo in the journal PLOS Medicine.31

Regarding SSRIs, there is a growing body of medical literature casting doubt on the serotonin hypothesis, and this body is not reflected in the consumer advertisements. In particular, many SSRI advertisements continue to claim that the mechanism of action of SSRIs is that of correcting a chemical imbalance, such as a paroxetine advertisement, which states, “With continued treatment, Paxil can help restore the balance of serotonin…”

Yet […] there is no such thing as a scientifically established correct “balance” of serotonin. The take-home message for consumers viewing SSRI advertisements is probably that SSRIs work by normalizing neurotransmitters that have gone awry. This was a hopeful notion 30 years ago, but is not an accurate reflection of present-day scientific evidence.

The ultimate question is whether the widespread use of anti-depressive medication poses any risks to patients. Here is what I have been able to find on this question:

  • There is a small but significant increase in the risk of diabetes for people taking anti-depressive medication.32,33
  • There is evidence that tricyclic anti-depressive medication is associated with an increased risk of cardiovascular disease, but this was not the case for Selective Serotonin Reuptake Inhibitors.34
  • A meta-analysis of 12 randomized trials of the impact of tricyclic antidepressants for the treatment of depression for children and adolescents concluded: “Tricyclic antidepressants appear to be no more effective than placebo in the treatment of depression in children and adolescents.”35,36
  • Discontinuing SSRI medication results in withdrawal symptoms such as nausea, headache, fever, trembling, panic attacks and hallucinations, which motivate people to go back to taking them.37,38 A recent investigation by the New York Times found that the number of people who have been on anti-depressive medication for more than two years has soared.39 More than 15 million Americans have been on them for five or more years. The primary reason is that the symptoms they experience when they try to withdraw drive them back to taking the medication.

Pharma Business Practices

Now let’s look at the facts I just laid out from the standpoint of the business of pharmaceuticals. Like all other corporations, pharmaceutical companies are organized to make money. They will naturally do what they can to maximize their profits. The numerous advances that have been made in finding effective drugs are largely the result of the motivation of companies to find new drugs that will increase their revenues and profits.

Companies have an incentive to do whatever they can to maximize their profit. The issue here—and for all the other industries that I discuss—is which practices we will allow and which we will prevent. In all of the areas I just discussed—the opioid epidemic, ADHD, resistant bacteria, and the treatment of depression—the pharmaceutical industry has contributed clear benefits. Opioids are effective in reducing pain and under the right circumstances, can be administered without resulting in addiction. Some children with high rates of activity and related problem behaviors may benefit from psychostimulants. Antibiotics are unquestionably beneficial, and cases of severe depression appear to benefit from anti-depressive medication.

However some of the practices of the pharmaceutical industry—and a network of researchers, physicians, and health care organizations they work with—are contributing to the deleterious outcomes I described above. Let’s look at the evolution of these practices.

Expanding markets. One of the best ways to increase your revenues is to find new customers. In each of the cases I describe, the companies have extended the uses of their medications beyond uses that were initially found to benefit people. Opioid use has been encouraged for longer periods then are needed and for problems that could have been addressed with other pain killers or behavioral interventions. Parents who are troubled by their young children’s fidgety and annoying behavior and physicians who treat those children have been encouraged to diagnose the problem as ADHD and prescribe psychostimulants. The pharmaceutical industry has marketed antibiotics to accelerate animal growth and to treat infections that are not bacterial. And when restrictions were placed on their use with animals in the U.S. the companies expanded their marketing to less regulated countries. In the case of depression, the industry and its allies in psychiatry have loosened the criteria for depression by, for example, redefining bereavement as a form of depression40 that should be medicated. And despite the fact that the only clear evidence for the efficacy of anti-depressive medication is for people with severe depression, 12% of American adults (29 million people) are taking anti-depressive medication.

Each of these moves has been quite profitable. For example, whatever the facts regarding the “true” rate of ADHD, the benefits of medication, the alternatives to medication, and the availability of other treatments, the huge increase in medicating children for ADHD has been very profitable to some of the drug companies. The sales of stimulant drugs prescribed for ADHD increased from $1.7 billion to nearly $9 billion between 2002 and 2012.41

An investigation by the New York Times41 attributed the rise to an extensive and successful marketing campaign by the makers of these drugs, which encouraged parents to view common problems of young children’s behavior, such as being fidgety, forgetful, or getting poor grades as symptoms of ADHD.

Lobbying to prevent controls on drug prices. In 2003, Congress passed a law to subsidize drug costs for Medicare recipients. The drug companies got an amendment to the law that prohibited Medicare from negotiating with the companies for lower drug prices. Given the volume of drugs that Medicare is paying for under this law, don’t you think they would have some leverage to negotiate lower prices? But despite the money that the government might have saved, many legislators who are adamant about reducing government expenditures voted for this bill. And certainly many of the people who voted for this bill are also adamant about the importance of free markets where buyers and sellers can negotiate to maximize their benefit. But in this case, free market advocates made an exception for the pharmaceutical companies.

Drug companies spend huge amounts of money on lobbying and on funding legislators who vote for what the companies want. According to Eric Pianin,42 writing for The Fiscal Times the drug industry spent more than $1.9 billion on lobbying between 2003 and 2016.42 Similarly, the companies gave $147.5 million to congressional and presidential candidates and super PACS in this period. Pianin cites a Center for Responsive Politics report that the industry spent the equivalent of $468,108 per member of Congress in 2015 and in the first nine months of 2016.43

Corruption of research on drugs’ efficacy. Research on the impact of drugs is supposed to be done in a way that ensures that only medications with clear benefits are approved. One way this is done is through double-blind placebo controlled trials. These are experiments in which people are randomly assigned to get the medication or to get a “placebo” a substance that there is no reason to believe will benefit the patient. Randomization assures that the two groups are very similar. In this way we can have confidence that any difference between them is due to the medication given to the one group.

However, people’s reactions to a medication—especially one that is designed to affect a behavior such as hyperactivity or depression—may be affected if they believe they are getting an effective medication. And they might be affected by what their physician says about the impact of the medication. For this reason, neither the physician giving the drug nor the patient is told whether they are getting the actual drug or the placebo. Both are blind to the patient’s experimental condition.

In addition, research that will be submitted to the FDA for approval must be done with high levels of scrutiny. I was one of the investigators involved in testing the nicotine patch that was created to help smokers stop smoking. We had to keep extensive records of our contact with each patient. We did not know which ones got the nicotine patches and which got patches without nicotine. Our records were audited to be sure that they were accurately kept. In the case of that study, we found that the people who got the patch (along with counseling, which the placebo group also got) were more likely to succeed in quitting smoking.

Despite these safeguards, the process of assessing drugs has gotten corrupted. Perhaps the most outspoken critic of the pharmaceutical industry is Peter Gotzsche, a professor of Clinical Research Design and Analysis at the University of Copenhagen. His 2013 book is titled Deadly Medicines and Organized Crime: How big pharma has corrupted healthcare. To say that his criticism is inflammatory is to put it mildly. He has chapters titled, “Organized Crime, The Business Model of Big Pharma”; “Very Few Patients Benefit from the Drugs They Take”; and “Pushing Children into Suicide with Happy Pills.”44

And yet his credentials as a scientist are impressive. His biography in the book indicates that he has published more than 50 papers in the five most prominent medical journals (British Medical Journal, Lancet, Journal of the American Medical Association, Annals of Internal Medicine, and the New England Journal of Medicine). In a foreword to the book, written by the Deputy Editor of the Journal of the American Medical Association, Drummond Rennie states that he trusts Gotzsche “to have his facts right. My trust is based on solid evidence, and on my own experience of several decades struggling with the results of pharmaceutical company influence upon my clinical researcher colleagues, and upon the public. I trust Gotzsche because I know him to be correct when he writes about events of which I have independent knowledge.” Drummond goes on to point directly to the contingency that is at the root of the problem: “To me nothing will help unless we disconnect completely the performance and assessment of trials from the funding of trials.”

Gotszsche claims that most clinical trials have been corrupted by the fact that the pharmaceutical industry is paying for them and the industry has a conflict of interest; their profit depends on a positive outcome of the trial. And indeed, there is strong empirical evidence that the outcome of drug studies funded by the pharmaceutical industry are more likely to conclude that a drug works than are studies not funded by the industry.45

Gotszsche gives examples of biases in the reporting of trials for three drugs for cardiovascular disease in which the number of heart attacks that were reported to the FDA in these trials were less than those reported by “a central adjudication committee in the publications.”

He indicates that one of the ways that the industry protects itself is by having agreements with investigators they are paying to conduct the trials that the company owns the data or would have the right to approve any manuscripts written. In this way the companies can suppress evidence that is not in their interest. Moreover, in many cases, the company also had the right to stop a trial at any time, another way in which unhelpful evidence could be suppressed. In addition, many of the contracts between companies and universities are themselves kept confidential, making it harder to determine whether the companies have undue influence over what data become available to the public.

One example of the problems involved in this, concerns the impact of SSRIs on adolescent suicides. When a concern arouse about the possibility that these drugs might be causing some adolescents to commit suicide, the investigators who had conducted the trials were unable to get access to the data, because some of the companies refused to provide it.

Gotzsche provides the details of one of the SSRIs, Paxil, which was tested with children and adolescents by GlaxoSmithKline in 2001. The published study reported that the drug was effective and minimal side effects. However, the Attorney General of New York sued the company in 2004 concerning fraud in relation to concealing harms of Paxil. The company’s internal, unpublished report indicated that eight children taking the drug had become suicidal, a rate significantly higher than for children taking the placebo. The FDA demanded that the company review the data again; that revealed four additional cases of “self-injury, suicidal ideation, or suicide attempt.” An internal company document stated, “It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine [Paxil].”

Gotzsche goes on to say that despite evidence that Paxil and Zoloft could induce suicides in children and adolescents, five million prescriptions a year were written for these drugs between 1998 and 2001. He then goes on to describes seven people who committed suicide after being prescribed an SSRI. None of them were diagnosed as being severely depressed, the only subgroup whom these drugs have been shown to benefit.

Gotzsche reports that three makers of SSRIs submitted data to the FDA in which they included suicide attempts of people who were randomized to the control group, prior to the beginning of the trial, but did not do this for those assigned to the intervention group. This reduced the difference in suicide rates between the two groups, making it less likely that a significantly higher rate of suicide would be detected in the intervention group.

Violation of the law. The corruption in the pharmaceutical industry is borne out by the prosecutions of companies. One of the ways that a company can make money is to simply violate the law. One might think that such events would be rare among wealthy professionals who run these companies. However, this is not the case. Here are just a few examples.

  • In 2007, Purdue Pharma and three of its current or former executives pleaded guilty to criminal charges that they had misled doctors, patients, and regulators about the risk of addiction for the drug OxyContin.46 The company paid a $600 million fine and those three executives paid $34.5 million in fines. According to the New York Times, the company took in $2.8 billion in sales on the drug during the six year period when they were fraudulently marketing it. None of the executives served time in prison. More recently, states and counties in the U.S. have initiated numerous lawsuits against Purdue Pharma. At this writing none of them have been settled. However, according to the Times, discovery in these suits has shown that the Sackler family, which owns Purdue was doing everything it could to promote the over-prescription of opioids. Once the epidemic of overdose deaths began, they started marketing drugs to treat the problem!
  • That the drug company campaigns were misleading is shown by the fact that “The Food and Drug Administration has cited every major ADHD drug — stimulants like Adderall, Concerta, Focalin and Vyvanse, and nonstimulants like Intuniv and Strattera — for false and misleading advertising since 2000, some multiple times.”41 For example, Shire Pharmaceuticals was fined $56.5 million for claiming that Adderall would normalize children taking the drug and improve academic performance, and prevent unemployment and criminal behavior.
  • Gotzsche44 cited ten cases in which drug companies have been convicted of fraud. Here are five of them.
    • Pfizer paid $2.3 billion in 2009 for fraudulently promoting four of their drugs and paying bribes to health care providers to get them to prescribe these drugs
    • Novartis paid $423 million in 2010 for illegally marketing an epilepsy drug and five other drugs, making false claims about their efficacy, and paying kickbacks to health care providers.
    • Sanofi-Aventis paid $95 million for overcharging US and local health agencies.
    • GlaxoSmithKline paid $3 billion for illegally marketing a number of their drugs for off-label use. (“Off-label” means prescribing the drug for a malady that it was not evaluated for.) The case also involved obstruction of justice, lying to the FDA, paying kickbacks to doctors, failure to include safety data, allegations of Medicaid fraud, and withholding incriminating documents.
    • AstraZeneca paid $520 million for illegally marketing an anti-psychotic drug to children, the elderly, veterans, and inmates for uses that it was not approved for. The uses, for which there was no evidence of benefit, included aggression ADHD, dementia, depression, mood disorder, post-traumatic stress disorder, and sleeplessness. The company paid kickbacks to doctors and spend lavishly on resort vacations for prescribing the drug.

Promotion by and to doctors. Once drugs are approved for use, the drug companies use advertising and promotion techniques to sell them—both to the physicians and patients. One way they do this is by paying physicians to speak to other physicians about the benefits of drugs. Often the physicians have been involved in evaluating the drugs. However, until recently the financial relations between these physicians and drug companies were not disclosed. When it came out that 84% of physicians were receiving payments, meals, free drugs, and free travel from the pharmaceutical industry,47,48 Congress passed the Sunshine Act to require reporting of all such payments.

But the Sunshine Act does not seem to have curtailed these practices. ProPublica49 reports that physicians were paid $6.2 billion by the pharmaceutical industry between August 2013 and December 2015. A further analysis by ProPublica showed that doctors who get more payments from drug companies are more likely to prescribe brand-name medications, even when cheaper generics of the same drug are available.

One of the physicians who received payments from the companies and promoted increased prescribing of narcotics defended his actions saying that his association with the companies “would benefit my educational mission, they benefit in my research mission, and to some extent they can benefit my own pocketbook, without producing in me any tendency to engage in undue influence or misinformation.”9 So long as the general public remains blind to effects of consequences on human behavior, people can get away with making such claims.

Advertising. Then there is advertising directly to patients—even children. For example, Shire the maker of Adderall for ADHD subsidized 50,000 copies of a comic book about drugs for ADHD. According to the New York Times report it uses superheroes to tell children, “Medicines may make it easier to pay attention and control your behavior!”41

Direct advertising to consumers is one of the biggest ways that anti-depressive prescribing is encouraged. They are designed to get people to consider that they may be depressed and to ask for a specific anti-depressive medication by name. As noted above, there is no evidence that people with mild levels of depression benefit from it, but one study showed that when patients asked for an anti-depressive medication by name it was prescribed 55% of the time.50

The argument for direct marketing to consumers is that it will increase the likelihood that people who need treatment will get it. But given the huge number of adults on such medication in this U.S., it seems equally likely that many people who won’t benefit from these drugs will get on them and will remain on them throughout their lives because of the difficulty in withdrawing from them.

Disorder creep—the loosening diagnostic criteria. One of the other ways in which drugs are promoted is by finding new disorders or loosening the criteria for diagnosing existing disorders. The diagnosis of psychological disorders is a case in point. The dominant system for diagnosing psychological disorders in the United States is the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association. Diagnoses are based on assessments of people’s behavior, not on the assessment of physiological processes. This is unlike the diagnosis of most physical illnesses, where there are measurable processes such as a bacterial infection, high levels of blood sugar, or occlusion of arteries.

The dominant view in psychiatry is that mental disorders are also due to clear biological conditions. However, the evidence does not support this view. There are not measurable physiological processes that can be used to diagnosis depression, ADHD, or schizophrenia. For example, the diagnostic criteria for depression are as follows:51

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2)52 loss of interest or pleasure.

  1. Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by other.
  2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day.
  3. Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day.
  4. Insomnia or hypersomnia nearly every day.
  5. Psychomotor agitation or retardation nearly every day.
  6. Fatigue or loss of energy nearly every day.
  7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day.
  8. Diminished ability to think or concentrate, or indecisiveness, nearly every day.
  9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

I submit that these criteria leave an enormous amount of the judgment to the physician as to whether a person is depressed. As I noted above, 80% of prescriptions for the treatment of depression are written by physicians who are not psychiatrists and many of those prescriptions are not written for depression. We should not be surprised, therefore, that 29 million Americans are taking anti-depressive medication.

I mentioned another example of disorder creep above—the shift in how bereavement is dealt with. Whereas, sadness due to the loss of a loved one (bereavement) was not a basis for the diagnosis of depression, the latest version of the DSM has eliminated that exclusion.40 It has thus become more likely that a person who is experiencing prolonged sadness over the loss of a loved one will be diagnosed as depressed and will be put on anti-depressive medication.

When I was doing behavior therapy in the 1970s I would often do an intake with a client who was highly distressed and would meet diagnostic criteria for depression. I would ask them about what was happening in their life and they would typically describe numerous difficulties—job loss, separation or divorce, conflict with a loved one. I usually found myself saying to them, “If I had experienced what you have experienced, I would be depressed too.”

Yet, the DSM has been revised so that experiences such as loss of a loved one or a job, divorce or a serious disease are no longer mentioned as reasons for not diagnosing a person for depression.44 The result is more people being prescribed anti-depressive medication.

Consider what might be the practical effect of this practice? Keep in mind that there is no evidence that anti-depressive medication works for people who are not severely depressed. Might it not be better if, rather than telling a person that they have a disease, that we help them figure out how they can cope with the important things that have happened in their life? Might it be that in this process, we will help people develop new skills and experiences that will ultimately, enhance their lives?

It is in this context, that we should consider what alternatives are available for helping people who are depressed. Here are viable alternatives that do not carry the risks of anti-depressive medication.

  • Behavioral Activation. This involves helping people learn to monitor their mood and daily activities, and increase the number of pleasant activities and positive interactions with their environment. A meta-analysis of sixteen randomized trials showed that compared with control conditions, it had a large effect (effect size .87) in reducing symptoms of depression.53
  • Light Therapy. Some people become depressed during winter months when daylight is limited. A meta-analysis of studies testing the impact of treatment with bright lights or dawn simulation (a gradual increase in illumination before the person wakes) have effects on depression that are equivalent to those found in pharmacotherapy.54
  • Omega 3 supplements. There are at least three randomized trials showing that omega 3 fatty acid has beneficial effects in treating depression. One study showed effects with patients with recurrent major depression. A second showed benefits for treating children (6-12) with major depression. The third study showed effects on patients with bi-polar depression.55
  • Acceptance and Commitment Therapy (ACT). I have already described ACT in detail in The Nurture Effect. ACT can be considered a form of behavior therapy. Rather than encouraging people to do what they can to suppress depression and other negative moods, it encourages them to become more mindful and accepting of them and to act in the service of their goals and values.

In short, there are numerous viable alternatives for the treatment of depression. Unfortunately they are not being promoted the way that pharmacotherapy is being promoted and they are not subsidized by insurance to the extent that pharmacotherapy is.

The Culture of Money Making

The corruption in the pharmaceutical industry is encouraged by the culture of wealth accumulation. Free-market ideology has made the accumulation of wealth the central feature of the business culture in many, though certainly not all, sectors of business. The widespread belief that the pursuit of one’s own financial gain will benefit everyone has distorted the culture of business in many industries. If my pursuit of economic gain will benefit others, then there is no reason why I should hesitate to pursue that gain. Indeed, the more I make the more I must be doing for others.

If I am correct, then we should not be surprised to find that industry leaders are making great amounts of money. And if I am correct that this invisible hand theory is not supported by the evidence, we may also find that in many cases, the general wellbeing is not advanced by increases in stock prices or executive salaries.

Our first question, then is “Are the Salaries of CEOs of Pharmaceutical Companies high?” The answer is yes. According to USA Today56 the top 14 CEOs salaries’ ranged from $8.7 million to $47.5 million in 2015. Taking a longer time span, the CEO of Gilead Sciences made $863 million since the Affordable Care Act was passed.57

Because such a large proportion of CEO pay is in the form of stock options, CEOs have a strong incentive to increase the price of their stock. According to an analysis of CEO salaries of health care companies, which included pharmaceutical companies, there is a close relationship between CEO salaries and stock prices.57 Obviously one of the ways that companies can increase stock prices is by increasing the price of drugs. That has certainly happened. The average price of drugs in the U.S. rose 98.2% between 2011 and 2016.58 And there are numerous examples of huge increases in drug prices that are not justified by any benefit to consumers or the contribution that the company has made to better health. Consider the recent practices of increasing the price of drugs that have been around for many years.

  • In 2015, Martin Shkreli, the 32 year old founder of Turing Pharmaceuticals, acquired a 62 year old drug, Daraprim, which is used to treat life threatening parasitic infections. He then raised its price from $13.50 a tablet to $750. In response to criticism he said “This isn’t the greedy drug company trying to gouge patients, it is us trying to stay in business. It really doesn’t make sense to get any criticism for this.”59
  • The EpiPen is a drug that can save the life of someone going into anaphylactic shock due to an allergic reaction, such as to a bee sting. Mylan, the maker of the drug raised its price over a five year period from $164 to $608.60 The CEO of Mylan, Heather Bresch, was paid $18.9 million in 2015.56
  • Gilead Sciences, which had a profit margin of 63.7% in 2015 was charging $84,000 for a drug to treat Hepatitis C.
  • Marathon Pharmaceuticals got permission from the FDA to charge $89,000 for a drug that treats children with Duchenne muscular dystrophy. The drug costs between $1,000 and $2,000 in Canada and Europe.61

The increases in drug prices are not due to these companies trying to survive—as Martin Shkreli argued. They are not only surviving, they are thriving: The top 11 drug companies had profit margins ranging from 25.3% to 62.7%.56

The United States spends far more per capita on health care than other developed countries–an average of $9,086 per person, compared with $2,802 per person in the United Kingdom.62,63 Expenditures on drugs account for ten percent of health care costs.64,65 Thus, while other parts of the health care system are struggling to control or reduce health care costs, the pharmaceutical industry is escalating prices with little regard to its impact on patients or the health care system.

In short, there is plenty of evidence that pharmaceutical companies are maximizing their profits in ways that harm those who cannot pay for their drugs and those who are harmed by the drugs themselves.

Making Pharmaceutical Malfeasance Unprofitable

In all of these examples, there are groups of scientists, practitioners, and journalist who are trying to stop medication practices that are doing as much or more harm than good. But dealing with it at the level of whether one type of drug should be prescribed less than it is fails to get at the root contingencies that are driving each of these harmful practices—namely the failure of government to regulate the practices of pharmaceutical companies so that the harms that may occur are carefully assessed and documented and the practices of companies that increase harmful prescribing are stopped. The prosecution of pharmaceutical company executives is one contingency that might reduce this behavior. However, the fines levied on companies for bad behavior, are typically less than the profit the companies reap. Whenever that is the case, then fines for bad behavior are simply the “cost of doing business.”

This is where a clear understanding of the impact of consequences on human behavior and the actions of corporations needs to be a guiding principle in our regulation of business. As long as harmful practices result in profits to corporations and income to corporate leaders, harmful practices will continue. Public policy needs to be that when a company engages in harmful behavior, they forfeit all profits and then some. If a company fails to make a profit, investors will stop investing and the drop in stock prices and the risk of bankruptcy will modify the behavior of corporate leaders.

None of this is likely to happen in a system of government where the companies whose practices are to be regulated have so much political influence that government is prohibited from taking effective regulatory action—or the regulators are members of the network of corporations that they have no motivation to take regulatory action. I discus what we can about this in Rebooting Capitalism.

(There is some hope that the criminal behavior of pharmaceutical companies is beginning to be addressed. John Kapoor, the founder of founder of Insys Therapeutics was recently sentenced to more than five years in prison for the fraudulent marketing opioids by his company. Four other executives are also being sentenced to prison.)

In closing, I think I need to occasionally mention that I do not write any of this to generate anger or animosity toward the leaders of these companies. I simply don’t think that it is strategic to do that. This series as a whole is describing a complex web of beliefs, values, organizations, and practices that must change. The thing that is needed across all of the examples in these essays is an understanding of the financial and social contingencies that are involved in their behavior. I have in mind not only the money that flows to the companies but the social reinforcement that occurs in the network of people who run these companies, serve these companies by providing legal counsel, public relations advice, advocacy for both their specific practices and for the generic practices such as limited regulation that are being promoted for the benefit of all companies.

Action Implications

Personal

  • Make sure that medications that are prescribed for you are necessary and effective compared to alternative strategies.
    1. For pain try non-medicinal strategy such as behavior therapy before taking medications. Refuse opioids if other pain killers have been shown to be effective. If you do take opioids, take them for a short period of time.
    2. If your child is behaving in ways that are listed as “indicative” of ADHD, be skeptical. Are they younger than other kids in their class? Consider that all of these behaviors are common in children and that medication may stunt their growth (not kidding). Read the first half of The Nurture Effect and seek competent behavior therapy before considering medication.
    3. If you or a loved one feels they are depressed, explore behavior therapy before considering anti-depressive medication. Chapter 5 of The Nurture Effect 66 describes behavior therapy treatments. And here are some more books you may find helpful:
      1. Get Out Of Your Mind And Into Your Life.67
      2. The Mindfulness and Acceptance Workbook for Depression: Using Acceptance and Commitment Therapy to Move Through Depression and Create a Life Worth Living.68
  • The Happiness Trap69
  • If you have a cold, don’t take antibiotics unless your doctor can convince you that you have a bacterial infection. Don’t buy meat from livestock that had been raised on antibiotics.
  • Tell your friends what you learned about pharmaceuticals. Spreading the word about harmful corporate practices will help to change their practices.
  • Support candidates who will impose consequences for malfeasance that eliminate the companies’ profits for harmful practices.


Policies

  1. In the pharmaceutical business and every other business, we need to monitor the impact of corporate practices to identify any that produce more harm than benefit.
  2. When a practice is show to be harmful, the company engaging in it must be penalized to an extent that the company does not just pay a fine, but instead loses money.


Organizations

  1. PharmedOut (https://sites.google.com/georgetown.edu/pharmedout/about-us/history?authuser=0). PharmaOut’s mission is to investigate the influence of pharmaceutical industry marketing on the practice of medicine; foster access to unbiased information on drugs; and create and promote pharma-free continuing medical education to providers.
  2. Undark, https://undark.org, provides scientifically accurate evidence on not only on pharmaceuticals (https://undark.org/article/big-pharma-influences-clinical-practice-guidelines/), but on most other ways in which science can benefit society.

Read the Full “Cultural Evolution of Social Pathologies” Series by Anthony Biglan:

  1. Introduction by David Sloan Wilson
  2. How Cigarette Marketing Killed 20 Million People
  3. The Right to Sell Arms
  4. How and Why the Food Industry Makes Americans Sick
  5. Big Pharma and the Death of Americans
  6. How Free-Market Ideology Resulted in the Great Recession
  7. The Fossil Fuel Industry: The Greatest Threat to Human Wellbeing
  8. The Crisis of Capitalism

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