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Are Addiction and Mental Illness Really Brain Diseases?

The two primary (New York) intellectual organs, the New York Review of Books and The New York Times, have recently featured two powerful cultural icons saying exactly opposite things.

Marcia Angell, the first woman editor-in-chief of the New England Journal of Medicine and now at the Harvard Medical School, in an ongoing, two-part series in the New York Review of Books (part 1 of which is in the June 23 issue), argues against the firmly ensconced American view that mental illness can be (and it has been) resolved to brain functioning.

The New York Times, for its part, once again supports, with a profile of Nora Volkow, the visionary director of the National Institute on Drug Abuse (NIDA), the slightly more come-lately view of addiction as a brain disease.

Angell has fought her way to cultural icon status by combating the medical-pharmaceutical-industrial complex, first in her position as editor of the NEJM, and subsequently from her ethics perch at Harvard (where she also sometimes treads on toes).

Angell is naturally led to an anti-brain-disease position because it has been fostered and foisted by the pharmaceutical industry with which she has been warring. Quoting her in the New York Review of Books, the modern “psychiatric revolution” appeared due to “the emergence over the past four decades of the theory that mental illness is caused primarily by chemical imbalances in the brain that can be corrected by specific drugs.” This revolution was spearheaded when the antidepressant “Prozac came to market in 1987 and was intensively promoted as a corrective for a deficiency of serotonin in the brain.”

Today, Angell points out, 10 percent of all Americans over the age of 6 are on antidepressants. This figure must grow, since younger Americans are being medicated at a much higher rate than current adults — there was a 350 percent jump in youth mental illness diagnoses in the two decades after the introduction of Prozac, a figure that continues to climb.

But this does not begin to tap the extent to which Americans are diagnosable for mental illness. A large survey by the National Institute of Mental Health “found that an astonishing 46 percent met criteria established by the American Psychiatric Association for having had at least one mental illness” at some time in their lives. And antidepressants are far from the most prescribed psychiatric meds in the United States (although they once were). “The increased use of drugs to treat psychosis is even more dramatic. The new generation of antipsychotics, such as Risperdal, Zyprexa, and Seroquel, has replaced cholesterol-lowering agents as the top-selling class of drugs in the US.”

This seemingly bottomless pit of mental illness in America — one that is never, ever reversed, or even staunched, no matter how many pharmaceuticals are thrown onto the marketplace — is actually the basis for the Angell series. It is titled, “The Epidemic of Mental Illness: Why?” One suspects that Angell’s answer in the second of the two-part series will be “pharmaceutical companies.”

Americans largely believe that their emotional problems are caused by brain imbalances that drugs redress.

I spoke with a highly intelligent, critical-thinking, young drug-policy reformer about antidepressants, which she swears by. She formed this judgment because her mother was bedridden with depression, and Prozac “cured” her. (I haven’t followed up with the woman, so I can’t say how permanent this solution has proved to be. But fall-offs from optimal performance by these medications — sometimes quite dramatic fall-offs — are standard.)

Such personal proof is people’s gold standard — if they see it in their own lives, they believe it. But this is actually no proof at all. People around the world swear by any number of cures that Americans would sneer at, and many “proven” therapies once broadly accepted in the United States have been thoroughly discredited. This is why the FDA demands that randomly assigned subjects with a given ailment be treated with a drug and the results compared to an untreated control group before they approve a medication for prescription to Americans.

The science and the psychology behind this are that, when people receive any psychiatric therapy, they invariably improve. There are three key reasons for this. In the first place (and this truth has been increasingly buried by the psychiatric revolution and the definition of emotional disorders as diseases), people tend to improve over time. When people enter therapy, they are often at a nadir, one from which they would rebound to a lesser or greater degree on their own no matter what is done for them.

The second reason for improvement is that people tend to respond to care, no matter what kind of attention, medication or therapy it represents. This bias, of course, is controlled for by administering a placebo treatment to the control group in a therapeutic trial. The comparison of the results between the treated and placebo groups allows for the calculation of the third contributor to improvement — the value added from actual therapy.

Which is where the first of the books Angell reviews, British academic psychologist Irving Kirsch’s “The Emperor’s New Drugs: Exploding the Antidepressant Myth,” comes in. Broad scientific clinical trials of antidepressants have never found that much value added from them. The amount uncovered in such trials, if taken seriously, would stun and disillusion providers and patients alike. I would say the range is a 5- to 25-percent measured advantage of antidepressants over placebos, with a mean of 15 percent.

But with every refinement of the placebo, the drug’s advantage declines. The best example is trials involving psychoactive placebos. If the placebo pill is inert, control subjects experience no chemical reaction of any kind. If the placebo is an active one, then the patient can say, “Oh, it’s kicking in.” When such psychoactive placebos are employed, the added improvement from antidepressants tends toward 5 percent.

Kirsch used the Freedom of Information Act to obtain all the trials drug manufacturers conducted on the key antidepressants, which they are obligated to present to the FDA. Many show no — or even negative — results. But overall results aren’t averaged by the FDA, who are only checking for several positive demonstrations of efficacy. For their parts, of course, the manufacturers publish only the positive results. Kirsch and his colleagues performed an even-handed analysis of all the submitted data. He then pinpointed studies with active placebos and other refinements, all of which reduced the detected benefits of antidepressants.

Angell notes:

Kirsch reported a number of other odd findings in clinical trials of antidepressants, including the fact that there is no dose-response curve — that is, high doses worked no better than low ones — which is extremely unlikely for truly effective drugs. “Putting all this together,” writes Kirsch,

“leads to the conclusion that the relatively small difference between drugs and placebos might not be a real drug effect at all. Instead, it might be an enhanced placebo effect, produced by the fact that some patients have broken [the] blind and have come to realize whether they were given drug or placebo. If this is the case, then there is no real antidepressant drug effect at all. Rather than comparing placebo to drug, we have been comparing ‘regular’ placebos to ‘extra-strength’ placebos.”

Robert Whitaker, a well-informed and passionate journalist, has written “Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America.” Whitaker’s point of departure is that, no matter how many more Americans with mental illness we identify and treat, the number continues to grow. After four decades when this has been true, the argument that we are simply divining people who were previously missed to receive extremely effective therapies is beginning to lose its sheen. This process seems to be self-fulfilling or, using medical terminology, iatrogenic.

This is not, strictly speaking, a scientifically based argument (as Whitaker is not scientifically trained). But Whitaker does refer to sound pharmacology when he notes that psychiatric drugs have long-term consequences that both cause the brain to rely on them (and to show withdrawal discomfort, often severe, when removed), and may actually depreciate brain functioning. The latter conclusion is based on some extremely spooky research. As described by Angell:

One well-respected researcher, Nancy Andreasen, and her colleagues published evidence that the use of antipsychotic drugs is associated with shrinkage of the brain, and that the effect is directly related to the dose and duration of treatment. As Andreasen explained to The New York Times, “The prefrontal cortex doesn’t get the input it needs and is being shut down by drugs. That reduces the psychotic symptoms. It also causes the prefrontal cortex to slowly atrophy.”

Whitaker’s conclusion is one that Americans would never even consider: we have basically a mental-illness-causing psychiatric system.

The last book reviewed, by Daniel Carlat, is “Unhinged: The Trouble With Psychiatry — A Doctor’s Revelations About a Profession in Crisis.” Carlat is a practicing psychiatrist, and perhaps as a result is not so radical as the other two authors can afford to be. And yet, in his calm presentation of the realities of psychiatric practice, the influence of drug manufacturers, and the distressing long-term trends in mental illness and our inability to get a handle on it, his book may be the most alarming of all. Carlat has no axe to grind, and yet he describes American psychiatry in a way reminiscent of the American economy — it has reached a point of declining results from which there is no return.

How does all of this reflect on the psychiatric “illness” model? None of these three authors believes the brain-chemistry-dysfunction version of reality. According to Angell, “the main problem with the theory is that after decades of trying to prove it, researchers have still come up empty-handed. All three authors document the failure of scientists to find good evidence in its favor. Neurotransmitter function seems to be normal in people with mental illness before treatment.”

Patients cannot be identified by pre-existing levels of any neurochemical or combination of them.

For these authors, researchers and Angell, the modern disease model of psychiatric illness is a myth. Whitaker wonders whether this myth is in fact harming us substantially:

The number of disabled mentally ill has risen dramatically since 1955, and during the past two decades, a period when the prescribing of psychiatric medications has exploded, the number of adults and children disabled by mental illness has risen at a mind-boggling rate. Thus we arrive at an obvious question, even though it is heretical in kind: Could our drug-based paradigm of care, in some unforeseen way, be fueling this modern-day plague?

As Angell notes:

Moreover, Whitaker contends, the natural history of mental illness has changed. Whereas conditions such as schizophrenia and depression were once mainly self-limited or episodic, with each episode usually lasting no more than six months and interspersed with long periods of normalcy, the conditions are now chronic and lifelong. Whitaker believes that this might be because drugs, even those that relieve symptoms in the short term, cause long-term mental harms that continue after the underlying illness would have naturally resolved.

Now that is an idea to contend with! Shades of Thomas Szasz.

There are remarkable parallels to the story that Angell unfolds in the Nora Volkow version of addiction — except, of course, her conclusion is exactly the opposite one. Volkow and her colleagues in and out of the NIDA measure brain and neurochemical changes due to various events — for example, use of cocaine. Her conclusion, now and forever, and “she must say it a dozen times a day: Addiction is all about the dopamine.”

What does that mean? Although drugs — and many other activities — cause distinctive changes in brain patterns, how does this equal addiction? “Well,” we might say, “the brain becomes dependent on the drug for the presence of dopamine (read ‘pleasure’), and this causes users to become addictively reliant on this neurochemical.”

Not quite. Problem one: different drugs impact this reward system very differently (the following quotations are from the New York Times article):

All addictive substances send dopamine levels surging in the small central zone of the brain called the nucleus accumbens, which is thought to be the main reward center. Amphetamines induce cells to release it directly; cocaine blocks its reuptake; alcohol and narcotics like morphine, heroin and many prescription pain relievers suppress nerve cells that inhibit its release.

Yet, these disparate processes are all posited to be similar in their ability to produce addiction.

Problem two: what about gambling and sex and video games. Are they addictive? Is this addiction due to the same chemical process? How does that work?

Problem three: dopamine stimulation or no, few people become addicted to the key addictive drugs even after repeated administrations: “Addicts and first-time users alike get the high that correlates with the dopamine wave. Only a minority of novices, however, will develop the compulsion to keep taking the drug at great personal cost, a behavior that defines addiction.”

(“First-time users” in this quotation from The New York Times is disingenuously misleading. Consider how most patients receive substantial supplies of narcotics in the hospital and may be given extended courses of pain-killers to take home, yet the vast majority don’t become addicted.)

Okay, so if not all users become addicted, then perhaps addicts do not produce or uptake sufficient dopamine naturalistically or have some other measurable neurochemical deficiency:

Researchers now postulate that addiction requires two things. First is a genetic vulnerability, whose variables may include the quantity of dopamine receptors in the brain: Too few receptors and taking the drug is not particularly memorable, too many and it is actually unpleasant. Second, repeated assaults to the spectrum of circuits regulated by dopamine, involving motivation, expectation, memory and learning, among many others, appear to fundamentally alter the brain’s workings.

Note first the last sentence, which is an extremely large escape clause based on the effects of a variety of experiences; moreover, these residual effects are hard to surmise in any one individual, forming what seem more like after-the-fact explanations than scientifically specified precursors.

In fact, no neurochemical or brain differences have ever been found between addicts and others prior to taking drugs. This is very similar to the (absence of) findings that Angell and the books she reviews note with mental illness. Only Volkow and like-minded people nonetheless maintain their optimism about this basis for the problem behaviors they study. Look at how Angell (quoting Whitaker) describes something that could as easily be said about addiction:

Prior to treatment, patients diagnosed with schizophrenia, depression, and other psychiatric disorders do not suffer from any known “chemical imbalance.” However, once a person is put on a psychiatric medication, which, in one manner or another, throws a wrench into the usual mechanics of a neuronal pathway, his or her brain begins to function… abnormally.

That there is something inherent in the person to be found there — in mental illness and addiction — is received wisdom, not empirical fact. The belief derives from the assumption that these phenomena are medical diseases, and all that remains is to find such inbred or pre-existing physical states — which, they feel, they will indubitably do. But scientific history is replete with tales where such precommitted assumptions turned out to be totally false.

Of course, Whitaker and Angel are also indicating that the introduction of pharmaceuticals create their own consequences — medical backlashes, we might call them. Read the following from Angell, keeping withdrawal in mind:

Getting off the drugs is exceedingly difficult, according to Whitaker, because when they are withdrawn the compensatory mechanisms are left unopposed [introduction of any neurostimulus produces a compensatory counterreaction, such that] when an antipsychotic is withdrawn, dopamine levels may skyrocket. The symptoms produced by withdrawing psychoactive drugs are often confused with relapses of the original disorder, which can lead psychiatrists to resume drug treatment, perhaps at higher doses.

This sounds a lot like… addiction. Rather than being a different medical category, reliance on psychoactive pharmaceuticals and addiction to the illicit drugs with which Vokow and the NIDA are concerned may be part of the same class of events — other than the setting and circumstances under which they occur, and the different types of people who rely on these different substances.

This brings us back to the major growing concern for Volkow and the NIDA, as reflected in The New York Times‘ front-page sub-headline on Volkow: “The scientist who leads the National Institute on Drug Abuse is facing a powerful enemy: prescription drug abuse.” But if these drugs operate exactly the same way as cocaine, heroin, amphetamines et al., why would we have expected any other result? This new development is actually a major dagger in the heart of the model which Volkow is using to fight addiction.

Finally, the title for The New York Times‘ Volkow profile is, “General in the Drug War.” It’s a funny designation for a scientist to call her a general in a war, especially since this particular war has been attacked by a growing number of public health voices as unwinnable and self-exacerbating. What this points to is that Volkow is not a free agent as a scientist and a researcher. Her employer insists that she say illicit drug use is irredeemably bad, while she previously had no mandate for commenting on — and was blind-sided by — the addictive potential and other downsides of pharmaceutical drugs.

Which is why the NIDA and government are now playing catch-up with prescription meds. It’s not a good sign for the underlying scientific veracity of the addictive brain disease model.

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