Cracked (9 page)

Scientists like Dr. Alan Branthwaite are not surprised by the power of placebo effects. I spoke to Dr. Branthwaite on a Tuesday morning in early February 2012. His manner was scholarly and cautious, but as soon as I raised the topic of placebo effects he became animated. “These effects are staggering when you first encounter them, and they still stagger me today,” he said. “The human body is so fundamentally linked to the mind that if you can spark the right mental associations, then the body responds, sometimes in dramatic and unexpected ways.”

Branthwaite won the medical community's acclaim when he published a paper in the
British Medical Journal
on placebo effects.
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What his study set out to discover was whether the presence or absence of a trusted brand name on a pill can affect recovery. “So we devised a neat experiment,” he said enthusiastically. “We gathered up about 835 women who regularly use painkillers for headaches and then randomly assigned them to one of four groups. And we gave each group a different pill. The first group had aspirin labeled with a popular brand name; the second group had the same aspirin but with no brand name; the third group had a sugar pill marked with the popular brand name; and the fourth group had an unmarked sugar pill. The question was which group would improve most?”

What Branthwaite and his team were expecting to find was a small increase in the effectiveness of the branded pills. “But what shocked us entirely,” he continued, “was the extent of that difference. The group given the branded placebos improved almost 20 percent more than those with the unbranded placebos, while branded aspirins also worked significantly better than unbranded ones. So here we had striking evidence that the presence of a trusted brand name can dramatically improve a pill's efficacy, even if that pill is completely inert.”

Taking these two studies together shows how surface things that may seem inconsequential to you and me (the color or brand name of a pill) are crucially important to the healing process. Subliminally they play with our expectations for recovery, and expectations, in fear of repeating myself, can dramatically affect outcomes.

4

To try to get to the bottom of how these meaning effects work, I spoke to Daniel Moerman, distinguished professor of anthropology at the University of Michigan. Moerman has dedicated much of his professional life to investigating how cultural meanings affect bodily functioning, and is widely known in academia as a world leader in placebo research.

I suggested to Moerman how odd it is that the meanings we ascribe to a pill can sometimes be more powerful than its active substance, especially in the realm of psychopharmacology.

“Well, James, you're an anthropologist, right? You know the power of meaning! Every culture has its symbols and objects of veneration and it is no different with us. Once, for us, we revered crosses and statues of the Virgin Mary, but now pills and stethoscopes capture our worship. So even an inert pill can affect us because it has shape and form and a context, and it has language attached. It comes in a blue box or a pink box, it's taken in a pharmacy, doctor's room, or hospital with all the panoply of a thousand years of medical tradition behind it to give it overwhelming symbolic weight.”

One of Moerman's recent studies shows how the power of medical sanction should not be underestimated.
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Medical approval is crucial to all of us, even the most critical among us. What Moerman did was gather up 117 studies of ulcer drugs published between 1975 and 1994 to discover what drugs worked best. As the results came in, he realized something astonishing.

In 1975 a new ulcer drug called Cimetidine was released. It enjoyed excellent clinical success, eradicating, on average, 80 percent of ulcers. As time passed, however, the drug's efficacy strangely became lower and lower, until today Cimetidine can only claim to eradicate 50 percent of ulcers. So what had happened to the pill? Moerman explains the deterioration by pointing out that five years after Cimetidine's release, a new drug called Ranitidine arrived. This competing drug was considered superior to Cimetidine, and as the new drug's popularity grew, the old drug's effectiveness declined. The correlation was staggering.

Of course, there are different interpretations of this (questions of changes in methods, etc.), but the most compelling, and to Moerman the most plausible, is that Cimetidine lost its power because as new and supposedly superior drugs arrived, Cimetidine ceased to be thought of as a superior drug. Belief in Cimetidine had waned, and with it so did its clinical effectiveness. “So it's clear,” said Moerman animatedly, “meaning matters!”

5

Let's now return to our original question. We know that Sarah was unaware that the drug she was taking was Prozac. She thought that Sarafem was a specific pill developed for her specific “problem.” Sarah was wrong. What Sarah also did not know was that Prozac was rebranded as Sarafem more for financial than scientific reasons.

But the question still remains about whether Prozac was rebranded for other reasons too. Was it rebranded because the company knew that Prozac would provoke only a small placebo effect in women suffering from so-called PMDD? Did Lilly turn Prozac into a distinctly female pill to achieve a higher placebo effect in this new patient group?

In order to answer this question, we first have to answer a broader one: Does Big Pharma more generally make use of placebo studies to manipulate higher placebo effects in patients? I put this question to Moerman.

“In my experience, people in the pharmaceutical industry are either incredibly good actors or are remarkably dense. They are good actors if they make use of these studies but pretend not to, and they are dense if they don't make use of them at all.”

So, to use Moerman's words, is the pharmaceutical industry led by actors or dunces? I decided to cut to the chase and find out for myself. I contacted Eli Lilly's headquarters in the UK and asked whether placebo studies are consciously used to create higher placebo effects in their consumers. The head of corporate affairs reluctantly responded after some prompting:

“I forwarded your enquiry to colleagues in our Global HQ, as only they would be in a position to answer. Due to competing priorities, they are unable to provide a response.”

Competing priorities? What did that mean? I politely wrote back asking Eli Lilly for some clarification. They wrote back curtly: “There is no Lilly response. Your questions are very specific and the person or people who might be able to answer them have chosen to decline on this occasion.”

So now you understand the problem. Questions like mine are rarely answered by the industry because there are just some things companies don't want you or me to know. Pharmaceutical companies are notoriously secretive. They have a history of not only concealing how pills are developed and marketed but of concealing negative trials that show their drugs in a bad light (as I'll show you in later chapters). So in the absence of corporate transparency, all we can rely on is indirect evidence to answer the actor/dunce question. Let's look at some of that evidence now.

We know that companies regularly pay academics to discuss their work with company employees and executives. We also know these companies have conducted their own in-house studies and data mining, and have in recent years funded the work of leading placebo scientists like Ted Kaptchuk and Fabrizio Benedetti (even Branthwaite's study of brand names I spoke of earlier was pharmaceutically funded). Furthermore, American journalist Steve Silberman recently exposed how a massive study of placebo effects (undertaken by the Foundation for the National Institute of Health) is being funded by companies including Merck, Eli Lilly, Pfizer, AstraZeneca, and GlaxoSmithKline. “In typically secretive industry fashion,” Silberman told me during our interview, “the existence of the project itself is being kept under wraps. FNIH staffers are willing to talk about it only anonymously, concerned about offending the companies paying for it.”

During our conversation, Silberman also mentioned that a few years ago when the Public Library of Science hosted a debate about whether the pharmaceutical industry should be allowed to continue advertising antidepressants to the general public, Randall S. Stafford, a senior consultant with Merck, GlaxoSmithKline, Bayer, and Procter & Gamble, argued that banning the ads might result in an abrupt reduction of drug effectiveness by reducing the placebo effect en masse.

“This was an astonishing and very rare admission,” Silberman said to me, “because the pharmaceutical industry won't publically acknowledge that the placebo response is giving a boost to the drugs they make. But here we had a major consultant openly declaring that the adverts are all about generating the expectations that help increase placebo effects, and that if you cut back on the marketing, the pills' effectiveness will dramatically decrease.”

Furthermore, again and again we find striking correspondences between what placebo research tells us and how actual pills are being developed. These correspondences strongly suggest that companies are taking account of placebo research when developing and marketing their pills. For instance, recall for a moment the study I quoted earlier that showed that blue sugar pills create sedating effects and red sugar pills create stimulating effects, even when both pills are made of sugar.

A team in the Netherlands has recently researched the actual colors of the pills that you and I take.
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And it turns out that nearly 80 percent of all sedative pills were green, purple, blue, or white (green, purple, and blue are sedating colors) while of all the antidepressants (uppers) only 5 percent fell into the green, purple, or blue category, 40 percent into the white category, and all the rest were colored in “stimulating colors.” Is it just coincidence that companies are manufacturing pills that largely match the placebo research?

Without being allowed to observe these companies at work directly (trust me, I and many colleagues have requested access countless times, but the doors remain closed), the question of whether companies are manipulating placebo research must continue to hang in the air. Of course the
indirect
evidence strongly suggests that placebo research is now regularly manipulated, that pills like Prozac are not just altered for reasons of marketing and money but because the features of Prozac, its color, its name, and its associations, would not successfully evoke the placebo response in women labeled with PMDD. Did these companies believe that women required a different pill, with different hopes and expectations attached, to get the result they wanted?

I know what I think, but given the absence of direct evidence, I'll just have to leave you to reach your own conclusion.

6

“Sarah, I have a question for you,” John says carefully. “Did you know that the drug you are taking is actually Prozac?”

Sarah's head tilts sharply to one side. “Excuse me?”

“What I mean is, did you know that Sarafem and Prozac are chemically exactly the same?”

Sarah sits back for a moment, looking at John skeptically. Then a sudden wave of anxiety flashes across her face. She sits forward sharply. “You're kidding me, aren't you?”

“I'm afraid I am not, Sarah.”

“But … but that's
wrong
, isn't it?” said Sarah, looking distressed. “Why would they do that?”

“Well, Sarah, that
requires a complicated answer.”

“But isn't Prozac for depression? I don't have depression.”

“No, you don't, or at least you didn't. The important thing is that since taking the pills you feel different. Perhaps we could spend a little time now thinking about precisely how you feel different. So before we do anything, I want to explore the role that the pills you are taking have played in how you feel now.”

“What, you mean that Sarafem may be responsible for why I feel different?”

“I don't know,” John responded. “It's possible. Even so, it is important for us to find out.”

“Jesus, I didn't know.”

“The sad truth, Sarah, is that most people don't …”

In the next chapter I shall reveal the strange ways in which antidepressants can profoundly change us. And I am not talking about “curing” us. I am talking about how they can alter our personality, sometimes in profound and unsettling ways.

So if you think the rabbit hole is already deep, it's now time to see how truly deep it goes.

MENTAL ODDITIES AND
THE PILLS THAT CAUSE THEM

O
n a popular daytime TV talk show in the UK, the host, Robert Kilroy, announces to the audience the wonders of a new antidepressant drug:
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Kilroy: This pill could solve all your problems. It is called Prozac. And it may mean the end of depression as we know it! [Kilroy approaches a female member of the audience and directs the microphone toward her]

Woman: I have been taking Prozac for two years.

Kilroy: And what difference has that made?

Woman: Brilliant!

Kilroy: Oh, she is smiling. [audience laughs] Her eyes are lighting up!

Woman: I feel as if I am back to normal. [she laughs]

Kilroy: You feel normal?

Woman: Yeah. [beaming a smile]

Kilroy: You feel like a better person?

Woman: Yeah, yeah. [smiling]

Kilroy: [turning to her husband]
Has
it worked? You look very dubious, my friend.

Husband: Apparently it has … but I can't help being suspicious of it. [looks sad and uncomfortable] I don't think she's the woman I married.

Kilroy: Why?

Husband: I think she has changed. [audience goes silent]

Kilroy: In what way?

Husband: I don't know. I don't know, but there is something … there is something there that is … different.

Kilroy: Okay, so she is not the woman you married. Is she a better woman?

Husband: No.(husband looks down sadly) She is … different.

In chapters 4 and 5, we saw that antidepressants have effects. Mostly they have placebo and side effects. Yet an increasing amount of evidence now confirms that for a subset of people they have other effects too—effects we don't yet fully understand. Like the woman on Kilroy's chat show, sometimes these pills make us “different.” Sometimes they sedate and numb us. And sometimes they change us in more unpredictable ways.

As this chapter unfolds, we will see that no matter what effects antidepressants unleash, these effects do not “cure” us or return us to “normality.” Instead, if we are to make any sense of their effects at all, we must regard them as we do other mind-altering substances—as jettisoning us into an abnormal state of mind.

By taking this view, I tackle head-on one of the most powerful myths embraced by the psychiatric establishment: that psychiatric drugs are capable of “curing” us and are therefore distinct from recreational drugs that merely alter our state of mind. What I am going to explore now is whether this “curing view” of antidepressants, far from capturing how these pills actually work, is rather a tale of convenience resting upon no solid, scientific basis.

2

In most British clinics and hospitals, before a patient is given psychotherapy like CBT or psychodynamic therapy, they usually undergo what is called a clinical assessment. These are interviews usually lasting about fifty minutes during which a psychologist or therapist assesses whether a given patient is suitable for therapeutic work. During these interviews the practitioner notes down the patient's problem, his or her personal and clinical history, and their understanding of the patient's problem. The aim of this meeting is to gather information with which to advise the clinical team on what kind of psychological intervention is needed.

Some years back, a colleague of mine conducted one of these assessments with a 52-year-old man I shall call Toby. A few months before the assessment, Toby had lost his wife to a long-standing heart condition. Her death had left him devastated. For the first time in his life, he said, he could truly understand what it meant to be entirely alone. He couldn't sleep, he could barely eat, and he was regularly incapacitated by heavy bouts of grief. After being consumed by his heartache for some weeks, he decided to visit his doctor for help. He was immediately prescribed antidepressants. After taking them for four weeks, however, some odd things started to happen. In the assessment, my colleague asked him precisely what these odd things were.

The first thing Toby mentioned was that he'd lost all capacity to cry. After a month on the pills, his tears had literally dried up. When my colleague asked him to elaborate, Toby responded that he no longer cried because he now experienced the memories of his wife in a different way. In short, the vivid “flashbacks” he used to have of his wife had now disappeared. He characterized these flashbacks as vivid bursts of recollection that would quite literally overwhelm him with the presence of his deceased wife, as if she were suddenly right there, alive and by his side.

His flashbacks would typically arrive at unexpected moments: when walking home he would suddenly see an image of her smiling and opening the front door; or when lying in bed he'd hear her voice or feel her hand stretching out for his own; or when on the train he'd glimpse her in the expression of a female stranger in a smile, a nod, or a look of concern. In these fleeting moments, his wife would become extraordinarily visible to him. And his body would respond with every sinew and fiber as if she were really there.

Yet she was not there. And that, he said, was what made these flashbacks so significant: their vividness meant that when they passed, he'd be left with a crushing sense of loss and grief. But since taking his pills, Toby told my colleague, these flashbacks had just stopped. Was this healthy? Was this natural? Toby now wanted to know.

There was also something else that the pills had changed. Before taking them, in those early weeks after his wife's death he'd regularly experience, almost on a daily basis, a dull ache growing in his chest. This would build and build, sometimes building all day until the pressure, unable to be contained anymore, would finally burst out through a deluge of tears. But, again, since taking his pills this internal pressure was somehow behaving differently. Instead of finding an outlet through his tears, he said it almost now seemed to get stuck in his head, agitating his thoughts and making him act in uncharacteristic ways.

One of these uncharacteristic behaviors involved religiously counting the number of lampposts he passed as he walked down the street. Another involved endlessly tracing the contours of distant objects with his index finger. For Toby, these acts had reached obsessive levels, but they did not end there. He'd also become addicted to online card games, which he now played deep into the night. He'd never played these games before, let alone stayed up late on his computer. He had always preferred other activities in the late evening, like reading. But he rarely read nowadays, as serious concentration was almost impossible.

As he spoke to my colleague he wondered openly whether this pent-up pressure was generating these “obsessive activities.” Of course he couldn't be sure, although he was worried that the pills had somehow cut off his emotions and forced him into his own head.

During the initial assessment, my colleague dutifully noted all of Toby's insightful reflections. That was his task. That's how assessments work. What his task didn't involve was exploring if the pills were responsible for the changes in Toby's behavior. Assessments do not afford the opportunity for that kind of enquiry. After all, if you choose to open Pandora's box you'd better do it in therapy where you have time to manage what may fly out, rather than in a time-restricted assessment where you don't.

But what if my colleague had more time? What if he and Toby had met in a different environment, one that allowed for a more frank conversation about whether the pills Toby was taking had affected him in the way he feared?

As such a question is hypothetical, it requires a hypothetical answer. That's what I'd like to provide now—an imaginative scenario of how things may have panned out had my colleague had more time. The purpose of imagining an exchange that never took place is to try and learn a little more about how the pills Toby was taking actually work and how they may have been affecting his life.

3

Please imagine the following exchange taking place in a drop-in center, where Toby has stopped by to ask my colleague for some advice.

Toby: I'm not sure what's happening to me. My emotions have become so flat. Is this normal? Are the pills responsible for this?

Colleague: It's difficult to be 100 percent certain what's responsible, because these changes may have occurred even if you'd not taken the pills. But on the other hand, we do know that antidepressants have effects. Mostly they have placebo effects and side effects. We also know that, for certain people, they can have sedating or numbing effects—perhaps the very effects that have interfered with your grieving.

Toby: So you're saying that if the pills
have
affected me, they've sedated rather than healed or cured me?

Colleague: Right. We misunderstand antidepressants when we think of them as curing us.

Toby: Could you elaborate? I am not sure what you mean.

Colleague: Well, antidepressants work differently from many drugs used in other branches of medicine. Take antibiotics and antiviral drugs, for example. When these enter the body, they attack the viruses or bacteria at the root of the illness. In this sense they cure us by literally killing the problem. The same can be said for chemotherapy, which is sent into the blood to destroy the cancer cells. But antidepressants don't work in that way, because when we're talking about emotional problems there is rarely an underlying pathology, virus, or disease to be cured [as I'll discuss in the next chapter]. Rather, these drugs, when they do have effects, therefore work more like substances that temporarily alter your state of mind, such as caffeine, coffee, or cannabis.
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Toby: So these pills don't
cure
us, they
change
us?

Colleague: Yes, they throw some of us temporarily into a foreign state of mind—into an altered version of who we are. This means they do not return us to normal health as medical pills aim to do. Rather, they alter our consciousness.

Toby: It sounds like you are saying these pills manufacture a new state of mind, perhaps even an unnatural state.

Colleague: Well, just think about it for a moment, Toby. Do you believe it's natural to stop crying after a terrible loss? I mean just like
that
? Grieving commonly goes on for a long time and drifts away only very slowly and intermittently. It's rare for it to just stop dead in its tracks, as it has done with you. Now, of course, some people may argue that you suddenly stopped because you were “cured” of an excessive emotional response. But that would be a silly argument, least of all because it assumes that grief is something we need to be “cured” from. No, it makes far more sense to say that in a situation like yours the pills have simply numbed your natural reaction to a deeply painful event.

Toby: You mean they've interfered with my normal responses?

Colleague: In your case, it may be so. After all, research shows that if you give Prozac to a group of healthy individuals, after a while about half of them will experience emotional blunting.
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So the question is what's happening to these healthy people? The pills certainly aren't “curing” them, because these people are healthy and have nothing to be cured from.

No, all that's happened is that the pills have dulled their normal reactions. These people have been thrown into a new state of mind manufactured by the drugs they've taken. So these drugs can sometimes produce effects beyond side effects and placebo effects, but often not the effects drug companies advertise—not healing, improving, or curative effects, as they say, but mind-numbing effects.
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Toby: But if the drugs I've taken have just numbed me, some people would ask what's wrong with that. Why shouldn't I just take that result and run! People use substances all the time to alter their moods. The use of alcohol is perhaps the most obvious example.

Colleague: Well, I see your point at one level. But the obvious answer is that numbing things isn't curing things, or even, in the long run, helping things. It's just providing a temporary and superficial distraction, and one that may store up problems later along the line.

You mentioned alcohol, so I'll illustrate what I mean with that example. Let's say I am really nervous about a party I've been invited to on Saturday night. And perhaps I am nervous because I think everyone there will be smarter than me, more attractive, more interesting, and what have you. Anyway, I get there and no one is talking to me, so I grab a drink and gulp it down. After a few minutes I relax a little and start up a conversation. And because I'm feeling a little better, a little more confident, I have another drink, and then another and another. Soon I am swaying all over the place, bumping into things, hiccupping, and chatting to everyone. Fine, so I am no longer nervous. But I am not my usual self either.

You see, although the alcohol has had an effect, it has not uprooted the reason I felt insecure in the first place. It's merely altered my state of mind so that I no longer
experience
my insecurity. It has replaced my feeling of inadequacy with a feeling of “what the heck,” a feeling that is neither a natural nor permanent product of my personality but a manufactured result of the alcohol I've drunk.

Toby: So the alcohol hasn't really changed anything fundamentally?

Colleague: Right. It's no more “cured” you of your insecurity than caffeine “cures” you of your tiredness. It's merely changed your state of mind while under its influence. And that's precisely how antidepressants work for some people—not curing us, but changing us. For you, your instinct was to cry, but the drugs seem to have cut that short. Your life is the same, your loss is the same, but your reaction to life events has now been altered. And so this raises a serious question about whether you've now just become like the guy at the party who's simply anaesthetized his problem. And if so, psychologically speaking, is being sedated to your pain really the best thing for you in the long run?