Medication

Drug companies and doctors

springflower

Happy 2009!  As promised, I'll start adding photos to brighten up the page, and maybe illustrate a point at times.  This one is a mid-winter tribute to spring.

As you might surmise from

past

posts

, I have long-standing concerns about commercial influence on the practice of medicine generally, and psychiatry in particular.  I have two bits of personal news to report on that front.  First, I authored the lead article in the current issue of

Ethical Times

, the quarterly bulletin of the

Program in Medicine and Human Values

established at the

medical center

where I teach.  Although

Ethical Times

eventually appears

online

, I may seek permission to reprint my article here.  Basically, I argue that it is incumbent upon ethical physicians to resist commercial influence in making clinical decisions -- whatever pharmaceutical companies or device manufacturers do or don't do.

Also, starting this month, I will serve as chair of the medical center's CME committee.  As I posted in October, continuing medical education (CME) is both required to maintain medical licensure, and is rife with potential conflicts of interest when funded, as most of it is, by industry.  It will be interesting to be on the front lines dealing with these challenges.

In related news, the Pharmaceutical Research and Manufacturers of America (PhRMA) recently revised and expanded its voluntary restrictions on interactions with physicians.  The full text is available here.  The relevant New York Timesarticle emphasizes the new moratorium on branded office items such as pens, notepads, and coffee mugs.  While my view is that the onus more appropriately rests with the medical profession itself to resist commercial influence -- and accordingly some groups have tried for years to convince doctors not to fill their offices with promotional giveaways -- this is a step in the right direction.  By my reading, though, the new PhRMA standards are considerably more limiting than the prior version in other areas as well.  New restrictions on wining and dining doctors may ultimately wield a bigger impact than the disappearance of cheap pens with drug logos.

Much more commercial influence remains, as an editorial in today's New York Times points out.  Meanwhile, in the current issue of the New York Review of Books, Marcia Angell, former Editor in Chief of the New England Journal of Medicine, presents the field of psychiatry as Exhibit A in a shocking review of undue industry influence on research and practice.  We still have quite a ways to go.

The customer is not always right

I often remind psychiatry residents that while a patient's treatment preference is important, it does not take the place of their own evaluation.  It is a bittersweet irony that many of us are mistaken about, or repelled by, what would most help us.

Some patients, with depression for example, only consider medications, and have tried many to no avail.  Even after a dozen adequate but unsuccessful medication trials by past psychiatrists, some call me in desperation to ask whether the 13th, usually with the newest heavily promoted product, could be the miracle they seek.  I generally tell them -- right on the phone -- that it is unlikely.  I also assure them that if they come in for an evaluation anyway, I will respect both their preference and past experience.  What I don't tell them:  People who avoid psychotherapy because they fear having to face uncomfortable memories or feelings often end up getting the most benefit out of it.  By the end of our first in-person meeting, I hope to engage such a patient's curiosity about his or her emotional life as more than simply a collection of symptoms.

Conversely, some patients pursue psychotherapy for years, and would never dream of taking psychiatric medication ("mind-altering chemicals").  This makes excellent sense when the problem is based on personality factors and relationship issues.  But sometimes it's not.  Even the best psychotherapy won't quell the hallucinated voices of schizophrenia, nor the behavioral excesses of mania.  Some patients are too depressed or anxious to use psychotherapy.  (And sometimes the problem is medical, not psychiatric at all.)  At these times it becomes my duty to advise medication, to explain why I do, and to explore with the patient their concerns and hesitation.

Some research says the best treatment for depression is a combination of medication and psychotherapy.  This often seems to be the case for problems other than depression, too.  As a psychiatrist I can provide one or the other or both.  And on rare occasions, neither:  A few patients have come to me who do not have a treatable problem at all.

The challenge for psychiatrists and other mental health professionals is that patients choose their own providers; they select us knowing their own preferences, and ours.  Persons who seek medication and not psychotherapy will likely see a psychopharmacologist who will share their viewpoint and only discuss medication.  Even more often, persons who seek psychotherapy and not medications (or a medical perspective) will see therapists who are not physicians.  Despite the advantages -- there are many more non-psychiatrists to choose from, and the fees are usually lower -- patient self-selection carries the risk of confirming their own prejudices.  It may sound harsh, but the "customer" is not always right.  It is incumbent upon us professionals to look past patient preference to what is most apt to be helpful -- even if we do not provide it ourselves.

Misuse of antipsychotic medications

A psychiatric revolution began in the late 1950s with the marketing of Thorazine, the first neuroleptic (antipsychotic) medication.  Thorazine and similar drugs quelled psychotic agitation and quieted auditory hallucinations (voices).  This allowed large numbers of state-hospital patients to be "de-institutionalized," i.e., released to the community.  While the ultimate promise of this revolution was broken in the U.S. by an inadequately funded community mental health system, the medications themselves were a huge leap forward.  In contrast to other types of tranquilizers and sedatives, neuroleptics specifically targeted certain psychotic symptoms, apparently due to effects on the brain chemical dopamine. Unfortunately, the neuroleptics brought many side-effects as well.  Stiff, shuffling, drooling patients became a common sight in clinics and on the street.  Thinking and reactivity were slowed.  Nearly all developed some degree of a chemically-induced form of Parkinson's Disease, and many suffered an irreversible movement disorder called tardive dyskinesia.  A few died of a severe reaction called "neuroleptic malignant syndrome."  These side-effects were well-known, noxious to the patient, and feared by doctors.  It took a condition as terrible as psychosis to justify using such harsh and potentially dangerous treatment.

In 1993 another psychiatric revolution was triggered with the marketing of Risperdal, the first widely prescribed "atypical" neuroleptic -- atypical in that it did not primarily act on the brain's dopamine, and seemed to lack many of the movement side-effects of typical neuroleptics.  Patients tolerated it more easily, and as a bonus it also seemed to help a wider range of psychotic symptoms ("negative" symptoms as well as the "positive" symptoms that the older drugs affected).  Other atypical neuroleptics were released: Zyprexa, Seroquel, and later Geodon and Abilify.  Psychiatrists soon switched most chronically psychotic, e.g., schizophrenic, patients to this new class of medication.

However, the atypicals brought problems of their own.  The first was price: Atypical neuroleptics cost several times as much as the medications they replaced, although some studies show this cost is offset by decreased hospitalization.  Several cause significant weight gain.  In recent years a metabolic syndrome has been identified where patients develop high cholesterol, diabetes, and related abnormalities.  There are risks of hormonal (prolactin) imbalance and heart arrhythmia.  While atypical neuroleptics may be safer than their predecessors, they are not safe medications by a longshot.

Nonetheless, new and expanded uses of the atypicals keep appearing.  Typical neuroleptics have long been used in the acute manic phase of bipolar disorder, not only for the psychosis that is sometimes present, but also as a sedative until the mood stabilizer (e.g., lithium) takes effect.  But the advent of atypical neuroleptics led to much wider use in bipolar disorder, i.e., ongoing maintenance use.  Eventually the FDA approved these medications as single-agent treatments for bipolar disorder.  Atypicals are also used widely to treat autism, ADHD, and simple agitation in children as well as adults (particularly demented elderly), as an adjunct to antidepressants (interesting discussion here), and even as simple sleep aids.

Considering the risks associated with atypical neuroleptics, they are being overused — misused — on a wide scale.  Indeed, today's New York Times reported that a panel of federal drug experts roundly criticized the cavalier use of these medications in children.  Adults, too, are being over-prescribed these drugs.  Useful for severe disorders, they are dangerous and unwarranted in the face of misguided complacency.

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.