Placebos (2)

In my last post, I wrote about the use of placebos in clinical practice -- or more accurately, about giving medical treatments based on psychological comfort, not physiological effect.  However, the area where placebos are most used and accepted is human research, not clinical practice.  Psychiatric research in particular introduces some interesting conceptual issues regarding the use of placebos. To decide whether any new medication actually helps patients, the "randomized, double-blind, placebo controlled study" is the gold standard.  In this type of experiment, research subjects who all have the same disease (or are all equally healthy) are randomly assigned to take either the new medication or a placebo: an identical twin of the medication lacking any of its active ingredients.  The subjects do not know whether they are in the medication arm or the placebo arm of the study -- they are "blind" to this fact.  Their doctor, or whomever rates their outcomes in the experiment, does not know either; this makes the experiment "double-blind."  If the only difference between the two arms of the study is the presence of the active ingredients, then any outcome differences, on average, between the groups can be attributed to those ingredients.

The reason such experiments are double-blind, and the reason for the placebo in the first place, is to separate the medication's physiological effects from any rating bias or placebo effects.  Outcome ratings can be distorted by raters' expectations; people often see what they want to see.  Placebo effects are psychological factors in the subjects that improve rated outcome.  These include wanting to please the experimenter by getting better, hope that the medication will work, improvement due to feeling attended to and cared for, etc.  A "controlled" experiment carefully dissects away rating biases and placebo effects, so that only physiological effects count.

There is great value in knowing that an antibiotic and a sugar pill lead to different medical outcomes.  Patients can feel attended to and cared for -- they can feel "better" -- and still die of infection.  Disease has a life of its own, apart from subjective experience.  Western medicine prides itself on its scientific foundation, and rightly so.  We don't want merely to feel better, we want to be better.

However, the situation is less clear with many psychiatric disorders.  Depression and anxiety, for example, do not appear to have lives of their own, apart from the patient's subjective experience.  If the patient feels better, he or she is better.  Thus, the rationale for placebo controlled studies in this area bears further reflection.  Why does it matter if mood or anxiety improvement from a medication is physiological, or "merely" a placebo effect?

One answer is that we hope to further our scientific/medical understanding of such disorders, and placebo controlled studies help us do that.  Another is that drug makers and the FDA justify the value of pharmaceuticals by virtue of their active ingredients, not the psychological features surrounding their use.  Yet another is that placebo effects are idiosyncratic and vary across the population, and we strive for more predictability.  Nevertheless, as discussed in my previous post, for a given patient it ultimately doesn't matter why a treatment works, as long as it really does.  (For a more technical discussion, see this British Journal of Psychiatry editorial.)

Another fascinating conceptual problem is whether and how to include placebo controls in psychotherapy research.  Psychotherapy, like depression and anxiety medication, treats distress that is inseparable from subjective experience.  Thus the importance of differentiating "active ingredient" and "placebo" effects is unclear at best.  In addition, the treatment itself consists of the very psychological influences a placebo controlled study aims to remove.

By analogy with medication studies, psychotherapy researchers have tried to isolate the "active ingredients" in therapy, and to fashion studies with a treatment arm and a placebo arm differing only by the presence of those ingredients.  So far, no active ingredient has been identified as essential (although the overall efficacy of psychotherapy is not seriously in question, see here and here).  What if there are none -- what if psychotherapy is all "placebo effect?"

This sounds like psychotherapy is quackery, much like the headline "Half of Doctors Routinely Prescribe Placebos" sounds like quackery exposed (see my previous post).  But if psychotherapy is compared not to medication but to other human relationships, the "active ingredient" idea seems out of place.  The helpfulness and support of a parent, teacher, spouse, sports coach, or minister cannot be reduced to any specific ingredient.  Growth or self-improvement gained from such relationships comes organically and emergently, not as a result of a discrete intervention.  This does not make the value of such relationships, or the benefits gained, any less real.

Placebos are essential for careful medical research, yet carry overtones of fakery and worthlessness.  When the placebo concept is applied in an overly broad fashion, its negative connotation can tarnish highly beneficial human interactions that are neither fake nor worthless.

Placebos (1)

The headline of a recent New York Times article was cause for public alarm: "Half of Doctors Routinely Prescribe Placebos."  A casual glance might have given the impression that doctors dispense sugar pills half the time, but this would be a misreading of the reported finding.  The article followed a research report that appeared in the October 23rd issue of BMJ (formerly the British Medical Journal).  A national survey of 679 U.S. internists and rheumatologists found that half routinely prescribe medication when, in the opinion of the clinician, the benefits "derive from positive patient expectations and not from the physiological mechanism of the treatment itself." This definition goes well beyond our usual notion of a placebo as a fake medication, e.g., a sugar pill or an injection of sterile salt water.  In fact, only two or three percent of the doctors reportedly used these.  Much more commonly the "placebo" consisted of over-the-counter analgesics (painkillers), vitamins, and sometimes antibiotics and sedatives.  Leaving the loaded word "placebo" out of it, half the doctors admitted to offering some treatments purely because they are psychologically comforting to their patients.

This nicely illustrates something psychiatrists, and many alternative/complementary healers, have known for a long time: There is no sharp distinction between mind and body.  Each affects the other.  Feeling ill and seeking help are not mechanical processes, like the engine light coming on in one's car.  A doctor's attention and concern can help a patient feel better even if no treatment is given.  Often medications work for no good reason, or fail to work when they "should."  The doctor-patient relationship is a complex dance of expectations and hopes, full of subtle cues and interactions at conscious and unconscious levels.  Western medical science shines a light so bright it can blind us as well as illuminate.  Of course doctors sometimes offer remedies that are primarily psychological.  How could anyone have thought otherwise?

While I have never given anyone a sugar pill, I have often been faced with choosing among several equally acceptable antidepressants for a patient.  The published efficacies, side-effect profiles, and even costs of the medications are essentially the same.  Just as I am about to throw a dart into my mental dartboard to pick one, the patient tells me of a friend who had great success with one of them.  Suddenly the choice is clear.  In such situations I (enthusiastically) prescribe that particular medication due to "positive patient expectations," and not due to "the physiological mechanism of the treatment itself."  To take another example, occasionally patients tell me that plain aspirin or Tylenol helps them sleep.  Who am I to tell them they must be mistaken?

The greatest cliche of medicine, "take two aspirin and call me in the morning," is a testament to this principle in internal medicine, rheumatology, and similar specialties.  If a newspaper headline in 2008 can shock and alarm us over a practice as old as this cliche, Western culture has strayed very far indeed from the essence of healing.

Psychiatrist as Gatekeeper

Lately I've been pondering one of my professional roles, that of gatekeeper.  Among my other duties, I help patients access things they already know they want, but cannot get without my help. Often this boils down to writing a "doctor's note": documentation to excuse a work or school absence, qualify for a discount transit pass, receive state disability payments, and so forth. The government or employer relies on me to verify the patient's entitlement claim. Metaphorically I stand at the gate, deciding whether to grant my patient passage. This role seems slightly odd if I think about it too long. After all, I do not work for the government or my patient's employer, and do not really owe them this service. I act on behalf of my patient. Yet professional ethics compel me at times to write reports exactly contrary to a patient's reason for seeing me in the first place. For instance, sometimes I must say that, in my view, a patient no longer qualifies for state disability. Although I work for my patient, I can end up opposing his or her wishes (which may be different than his or her ultimate interest).

Perhaps the starkest example of this is applying an involuntary legal hold when a patient is acutely suicidal or otherwise dangerous.  Psychiatrists tend to think of this as acting in the patient's best interest -- reassuring ourselves that most patients would thank us later when in a calmer and more rational state of mind.  In fact, many do.  However, some critics of psychiatry point this out as evidence that we are "working for the state," not our patients.

A related awkward twist on the gatekeeper idea is my growing role as a medication gatekeeper. By this I mean being asked to write a "doctor's note," in the form of a prescription, for a medication the patient has already decided he or she wants. A number of potential patients call nowadays having researched their symptoms online, or in some other way having concluded they need a specific medication. They are not seeking my professional opinion or advice, just the prescription.

As with the other kinds of "doctor's notes" mentioned above, professional ethics compel me to do a good-faith evaluation, and only write the prescription if I believe it is medically indicated. A few patients have fired me in frustration when I did not write the prescription they wanted, my carefully explained rationale notwithstanding.

This is another situation that seems slightly odd if I think about it too long. For one thing, prescription drugs are available from other countries online and without a prescription, although ordering them this way is illegal in the U.S. and potentially dangerous. Thus, in calling me, patients who could otherwise order directly online are taking extra time and expense to get medications the legal and safe way. Yet they are doing so in a manner that attempts to sidestep the safety features built into the process.

Government oversight and regulation of drugs in the U.S. extends back to the late 1800s and saw a turning point in the 1938 Food, Drugs, and Cosmetics Act.  Soon after its passage, the FDA began to identify drugs considered unsafe for direct use by patients; they would require a physician's prescription.  However, all legal medications were available over-the-counter until the Durham-Humphrey Amendment of 1951, which revised the 1938 Act to formally distinguish between prescription and over-the-counter medications.  This was when physicians became medication gatekeepers.  The idea was to protect the public from itself, to impose controls on the use of substances that are addictive, easily misused, laden with common and/or dangerous side-effects, or carry other possibly hidden risks.

However, Americans have decidedly mixed feeling about the state's role in "protecting the public from itself."  Traditionally, liberals have favored it and conservatives have opposed it when an issue (e.g., gun control) is framed as one of safety.  Conversely, when an issue (e.g., recreational drug use) is framed as a threat to the moral fiber of a community, conservatives favor state control while liberals oppose it.

Prescription medications carry both safety and "moral fiber" implications, and often I feel caught in the middle of these swirling political eddies.  Not only am I compelled by professional ethics to be a medication gatekeeper if someone sees me for a prescription, it frequently strikes me as the only sensible arrangement.  I know about diseases, drug interactions, and other important, relevant facts that the average person does not.   In some cases self-prescribing would be like walking through a minefield blindfolded.  But other times I find myself wishing the patient had left me out of the equation entirely and simply ordered online.  Adult Americans make many, many decisions for ourselves that may be ill-advised and shortsighted, but we are free to make them anyway.  In those cases I feel I am part of an interaction that neither party really wants.

Being a gatekeeper is not why I became a psychiatrist.  For most of us, it is an awkward, ill-fitting role for a profession that ideally reflects empathy, collaboration, and cooperation.  I much prefer being a medication advisor than a rubber-stamper (or roadblock); fortunately, psychotherapy is by nature collaborative and rarely feels like gatekeeping.  I am sure I will continue to ponder all of this, and I welcome your thoughts as well.

Thanks, Dr. Carlat

Daniel Carlat MD of the popular Carlat Psychiatry Blog, linked to my post about nearly becoming an unwitting speaker for Wyeth.  He recounted his own experience speaking for Wyeth in a great New York Times Magazine article last year.  Thank you, Dr. Carlat, for welcoming me into the psychiatric corner of the blogosphere.

Almost a speaker for Wyeth

In my last post, I wrote about how the pharmaceutical industry funds half of the continuing medical education (CME) of doctors, and the risk this may pose for bias in what doctors learn.  The influence of industry money on health education goes far beyond this, though.  In 2004 I learned first-hand how insidious this influence can be.

I was the medical director of the mental health clinic at California Pacific Medical Center (CPMC) in San Francisco.  One day the hospital's Community Health Resource Center asked me to participate in a public talk on depression and its treatment.  The seminar at a large downtown hotel would feature an actress named Delta Burke who had triumphed over her own depression, a representative from the Mental Health Association of San Francisco, and myself.  I would spend 20-30 minutes on recognizing clinical depression and outlining treatment options.

I've been an educator my whole career, and was immediately enthused by this opportunity.  It was sponsored by my hospital, the Mental Health Association of San Francisco, and a public relations firm I had not heard of, Porter Novelli.  Although I was wary of drug companies using such talks as marketing tools, there was no apparent industry connection.  I agreed to do it, and asked the caller for any written materials they had to clarify the format.

A number of weeks passed.  It may have been only a week before the talk when I received a press release, an outline of the event, and a promotional flyer headlined "Life Beyond Depression: Delta Burke Speaks Out."   I learned that San Francisco was the fourth stop of a national tour called "GOAL! (Go On And Live!)" featuring Ms. Burke.  Her message was that, "... it is possible to virtually eliminate the emotional and physical symptoms of depression and go on and live."

I, too, was listed as a speaker on the press release.  It said I would "discuss the warning signs of depression, highlight treatment options, and explain why the virtual elimination of symptoms is the goal of treatment."

The repetition of this "virtual elimination" phrase made me suspicious.  I went to the GOAL website (now defunct).  It looked like an innocuous public education effort about depression.  There was no mention of any specific antidepressant, although "virtual elimination" was mentioned there, too.  Then I saw that the site was copyrighted by Wyeth Pharmaceuticals, makers of the antidepressant Effexor.  It all started to make sense: Effexor's advertising campaign at the time touted the drug's ability to lower scores on the Hamilton Depression Rating Scale to near-normal levels, i.e., to "virtually eliminate" symptoms.

I explored the Porter Novelli website until I found a page that described their public relations efforts on behalf of their client Wyeth and its product Effexor, including the GOAL website and the series of talks by Ms. Burke.  (Although that page is now gone, this blog entry from 2002 clearly links Wyeth, Porter Novelli, the "virtual elimination" phrase -- and even Dr. Nemeroff, who was the lead investigator of the study that triggered Wyeth's promotional campaign.  A 2002 Wyeth press release documents the campaign as well.)

I felt I had been duped.  I imagined turning the tables by standing at the lectern in the Grand Hyatt ballroom, and instead of giving a talk crafted by Wyeth's PR firm, I would instead astonish everyone by revealing the subterfuge.  I would declare that the audience and I were lured there under false pretenses, as a crass marketing ploy.  My denouncement would make the papers.

Of course, it didn't happen that way.  I told the Community Health Resource Center I refused to participate in a veiled pharmaceutical promotion, and suggested they follow suit.  Instead they called my chairman to find a last-minute replacement, while someone from GOAL called and pleaded with me to reconsider.  My chairman opined with some irritation that our department was obliged to provide someone.  And so he did the talk himself, presumably extolling the "virtual elimination" of symptoms just as Wyeth and their PR firm had planned.

My chairman and the Community Health Resource Center, and perhaps the city's Mental Health Association as well, saw this event as constructive public outreach despite the commercial overtones.  I could not.  It concerns me when education for the public, or CME for physicians, conceals a disguised ulterior motive.  For me, this experience underscored how easy it is to re-brand product promotion as education, and how vigilant we doctors must remain in order to avoid unwitting enlistment in those commercial efforts.