Psychopharmacology: the art of treating the synapse

When the guards escorted the young man out of the room you could hear the steel shackles slap against the linoleum tiles like a slinky. Methodically, he shuffled out, trussed up in a heavy leather straight jacket. He hadn’t said a word during the interview, which lasted all of fifteen minutes, at the most twenty.

The psychiatrist scribbled the medication orders on the young man’s chart and handed it to the orderly. Afterwards he carefully slipped the pen into the pocket of his white dress shirt under the lapel of his tweed sport coat, and the four of us exited past the heavy steel door with the small thick mesh-reinforced glass window. We passed through a series of check points and stepped out into the warmth of spring sunshine.

“That’s what I appreciate about you — about your approach to the patient,” the medical director was saying to the psychiatrist. “At least you make an attempt to talk to these kids before deciding to push up their meds. Your predecessor just wrote the orders. He didn’t seem all that interested.”

“You’ve got to document the rationale for making those adjustments,” the psychiatrist said, slipping a hand into the pocket of his trousers. “Still, many times you’re forced to push up the dose until you see some sort of clinical response.”

“As long as we avoid any violent outbursts,” the administrator said. “I like to have a nice clean calm operation around here.”

I tagged along behind them, relieved to be able to take in the fresh uninhibited air.

“So what’s your overall impression so far, young man?” the administrator asked me. “You think you might consider a position in the prison system?”

I coughed a non-committal answer.

“Give him a chance,” the medical director said. “He hasn’t seen the rest of the operation yet.”

I was certain that nothing I might see could induce me to consider taking a job as a physician assistant in this maximum security prison. This was back at the time when folks were complaining bitterly about the recent increase of the price of gasoline — it had just surged to 69 cents a gallon at the pump.

Eventually, I elected to pursue a career in pediatrics. I enjoyed interacting with children, fascinated by their growth and development. I had come to a point where I realized that if I wanted to have some sort of positive impact in the lives of other human beings, I probably needed to intervene in a meaningful way before their first birthday.

The field of child psychiatry has mushroomed over the span of my professional career. Thirty years ago psychopharmacology played a minor role in primary care. Since the turn of the 21st century, psychosocial issues have moved to the forefront in pediatric practice. Nowhere has this become more evident than in the surge of prescriptions written for psychoactive drugs in children. Experts estimate that at present nearly 3.5 million children regularly take some sort of prescription medication for a psychiatric condition.

Such statistics give one pause to reflect on the development of this phenomenon. Why have the last several generations of children born in the U.S. suddenly developed ADHD, anxiety, depression, and bipolar disorder in epidemic proportions? Has there been some sort of random genetic drift at work on the molecular level in this population? Or could it be that we are dealing with a medical paradigm shift — the way in which we consider what constitutes the origin of illness in human beings?

Over the past decade research has demonstrated a relationship between traumatic childhood experiences and the development of chronic illness in adults through behaviors like smoking, heavy drinking and overeating. We now know that early adverse events are capable of altering the chemistry of DNA in the brain. It may be that many chronic illnesses we see in the adult population — lung cancer, liver disease, diabetes, hypertension, heart disease, depression, substance abuse — are the direct result of a sort of generalized post-traumatic stress disorder in childhood.

It is one thing to consider a child from the standpoint of his behavior. Behavior can be shaped through the use of positive and negative reinforcement, something that parents and psychologists have known for decades (if not centuries). But when we view the behavior in the young child as the end result of neurotransmitters stimulating selected synapses in the brain, the treatment changes drastically.

In treating infectious disease, clinicians are taught to match the bug with the drug: isolate the causative organism and prescribe an antimicrobial that targets it. The drug kills the bug, and the patient is cured of the malady.

We have come to the point where behavioral issues in children are regarded as the result of biochemical imbalances in the brain. If the observed behaviors portend a relative deficiency in serotonin, a selective serotonin uptake inhibitor is prescribed. With our modern psychopharmacological armamentarium we can manipulate cerebral neurotransmitters at will — many times with fuzzy results, but we’re making progress. Designer drugs, ones tailored to target specific synapses, are in the pipeline. The day is swiftly approaching where we will be able to shape human action — perhaps even human thought — through psychoactive medications.

Whether that is desirable or not is another question entirely — one which we as a society need to think long and hard about. Over three million human brains in various stages of development have already been subjected to psychopharmacological manipulation, the long-term side effects of which are as yet unknown.

What’s in a name?

What’s Montague? it is nor hand, nor foot,
      Nor arm, nor face, nor any other part

      Belonging to a man. O, be some other name!
      What’s in a name? that which we call a rose
      By any other name would smell as sweet.

Specific to the nomenclature of the physician assistant profession, the issue has become that, in this day and age, PAs no longer “assist” primary care physicians; rather, they practice with them as associates. Physician assistants have been integrated into not only primary care but practically every medical subspecialty in existence.  more»

Mesofacts and Megatrends

At the conclusion of a continuing medical education lecture, my ears perked up.  The speaker had been asked a question from a member of the audience:  what pathogen comes to mind when considering a diagnosis of conjunctivitis and otitis media in the pediatric patient?  His answer:  pneumococcus.  I was stunned.

Since my early days in training I had been taught that the clinical syndrome in question — conjunctivitis-otitis media — was nearly always associated with non-typeable Hemophilus influenzae.  Suddenly the pathogenic tables had been turned.  How could that be?

Any practitioner of medicine knows that nothing is ever set in stone in clinical practice.  From diagnostic criteria to clinical syndromes to etiologies to treatment:  everything, it seems, is in a constant state of flux.

Recently, I learned that what I had encountered here was a mesofact: a fact that changes slowly over the course of years or even over a lifetime.

Many facts that we learn in school and hold on to with dogmatic certainty morph into mesofacts.  One day we wake up to find out that things “have changed, changed utterly.”  The pathogen responsible for pediatric conjunctivitis-otitis media syndrome is just one example.  We recognize rapid change almost immediately; we are slow to pick up on those small subtle seemingly insignificant changes that occur over time.

In a Boston Globe article Samuel Arbesman, a postdoctoral fellow in the Department of Health Care Policy at Harvard Medical School, quotes a few interesting mesofacts:

  • Since the 1970s twelve new elements have been added to the Periodic Table.
  • The percentage of the world population that uses mobile phones has jumped from 4% in 1997 to nearly 50% in 2007.
  • Since 1995 the number of planets newly discovered outside our solar system has risen to over 400.

Mesofacts have always been part and parcel of medicine.  Yet I can’t help but ponder the difference between mesofacts and megatrends in medical practice, for not all of our latest technological and pharmacological armamentaria are brought to bear on mesofacts.  Megatrends can masquerade as solutions to medical dilemmas as well.

A few examples:

Mesofact: the incidence of asthma in the general population has increased exponentially over the past two decades.

Megatrend: inhaled corticosteroids have become the standard maintenance medication for asthma treatment during the same time period.

Mesofact: the diagnosis of pediatric ADHD has mushroomed over the past three decades.

Megatrend: the number of psychoactive drugs for ADHD routinely prescribed by general pediatricians has skyrocketed over the previous twenty years.

Mesofact:  20% of the general population suffers from clinical depression at some point in life.

Megatrend:  the SSRI class of antidepressants has risen to the rank of most prescribed psychoactive medication in the USA.

Astute readers will note that in each of the above examples mesofacts and megatrends can be interchanged with little difficulty.  This brings up the question:  which drives what?  Do mesofacts drive megatrends, or do megatrends influence mesofacts?

Is the use of inhaled corticosteroids as standard treatment of asthma based upon the mesofact of the increased incidence of asthma in the general population or upon treatment trends underwritten by the pharmaceutical industry?

Is the widespread prescribing of psychoactive drugs for the treatment of ADHD and childhood bipolar disorder based upon a true increase in the incidence of those disorders or upon treatment trends?

Is the increased incidence of autism in the pediatric population a mesofact or the direct result of trends in diagnosis?

In medicine which comes first — the mesofact or the megatrend?

Are mesofacts in fact facts?  Or in some instances are they merely created by megatrends?

Recommended reading

In preparation for a routine medical checkup, a good friend of mine drafted a list of concerns to discuss with his physician.

Even though my friend’s life now spans seven decades, he remains in reasonably good health.  Like most of us, he’s got some minor issues related to the wear and tear of his body over time, but nothing insurmountable.

He sat and thought and jotted a few items down on paper.  First he listed his current medications.  Then he wrote a short note to remind himself to mention the problem of his ongoing knee pain.  After that he recorded his concern about his recent inability to remember where he puts things.  Lastly, he added a particularly worrisome problem—inability to rest at night because of recurring bad dreams.

My friend enjoys talking with his doctor, because, as he puts it, his doctor always takes the time to listen.

Whenever my friend checks in with the receptionist for his scheduled appointment, he always inquires just how far behind the doctor is running.  The usual answer falls somewhere between one to two hours.  Undaunted, my friend takes a seat and opens whatever reading material he has brought along to pass the time until the nurse calls his name.

One recent morning over breakfast my friend shared the notes he had taken down during this latest doctor visit.  One by one we reviewed the issues.  When it came to the sleep problem, I asked him what his doctor had advised.

“Oh, he said I should read Thoreau’s Walden,” he told me.  “He feels that it’s a good book to cleanse the mind.”

On hearing this advice, I smiled.  I re-read Walden every spring.  Perhaps that’s why I haven’t been plagued with disturbing dreams for years.

Walden is melting apace. There is a canal two rods wide along the northerly and westerly sides, and wider still at the east end. A great field of ice has cracked off from the main body. I hear a song sparrow singing from the bushes on the shore,—olit, olit, olit,chip, chip, chip, che char,che wiss, wiss, wiss. He too is helping to crack it. How handsome the great sweeping curves in the edge of the ice, answering somewhat to those of the shore, but more regular! It is unusually hard, owing to the recent severe but transient cold, and all watered or waved like a palace floor. But the wind slides eastward over its opaque surface in vain, till it reaches the living surface beyond. It is glorious to behold this ribbon of water sparkling in the sun, the bare face of the pond full of glee and youth, as if it spoke the joy of the fishes within it, and the sands on its shore,—a silvery sheen as from the scales of a leuciscus, as it were all one active fish. Such is the contrast between winter and spring. Walden was dead and is alive again. (“Spring” in Walden)

Minding your grammar

While perusing articles on health care in the medical literature as well as in the lay press, I frequently run across the misnomer “physician’s assistant.” What the author really means, of course, is “physician assistant,” the established nomenclature for our profession.

Does that crucially placed terminal “apostrophe s” really matter? Apparently so, according to a recent New York Times article on IBM’s master computer, Watson.  more»

“Notes from a Healer” — True Grit

Two identical surnames appear back to back on my morning patient roster: a sister and brother, both scheduled for physical examinations. I haven’t seen either one for several years. When economic times are hard, the family income only goes so far. You cut corners where you can. If the kids aren’t sick, why bring them to the doctor? more»

My latest installment of Notes from a HealerTrue Grit — is now online, newly published in the Yale Journal for Humanities in Medicine.

The Yale Journal for Humanities in Medicine is an online journal fostering discussion about the culture of medicine, medical care, and experiences of illness. Interested readers can access a list of editorial board members and regular contributors here.

Minimal Medicine

Sometimes I wonder whether we as a society have not over-medicalized life. We spend so much of our time browsing health columns, monitoring vital signs, ruminating on our symptoms, consulting our doctors. Many of us have become so health conscious that we balk at deviating from the straight and narrow path. When it comes to our health, we have become risk averse.

Even those of us who spend their days in clinical practice recognize that medicine does not encompass all of life.

Perhaps we need to learn to practice minimal medicine.

These thoughts ran through my head as I read Mark Bittman’s final NYT Minimalist culinary column. Over a span of thirteen years Bittman authored nearly 700 weekly columns for the NYT Dining section. As it turns out, the culinary arts share a good deal with medical practice.

“I discovered that you never cook with someone else without learning something,” Bittman writes. “In every case, there’s a two-way transfer of knowledge. If they know less than you do, you grow from teaching. If more, of course, you grow from learning.”

Bittman’s words bring to mind Sir William Osler’s description of medical teacher and student: “the pupil and the teacher working together on the same lines, only one a little ahead of the other. This is the ideal toward which we should move.” After 25 years of practice, Osler observed, “I have learned … to be a better student, and to be ready to say to my fellow students, ‘I do not know’.”

Osler reckoned that “no man can teach successfully who is not at the same time a student.”

Here’s Bittman musing again: “Usually, I was either taught to make something or I modeled it myself, as best I could. I refused to buy into the notion that there was a ‘correct’ way to prepare a given dish; rather, I tried to understand its spirit and duplicate that, no matter where I was cooking.”

Osler advocated that “the practical shall take the place of didactic teaching.” To acquire the skills necessary to perform medical procedures, students are encouraged to “see one, do one, teach one.” In 1867 the physician Oliver Wendell Holmes argued that the “most essential part of a student’s instruction is obtained … not in the lecture-room, but at the bedside.”

Bittman maintains that, “as Jacques Pépin once said to me, you never cook a recipe the same way twice, even if you try.”

How true. And you never perform a physical examination or surgical procedure in exactly the same way. There are always confounding factors which necessitate workarounds and thinking outside the box.

Medical practice, like cooking, is always a compromise. Like their culinary counterparts, clinicians “almost never have the time, the ideal ingredients or equipment, or all of the skills we’d like.”

“Shop avidly, keep a full refrigerator and pantry,” Bittman advises; “pull things out and get to work.”

Where would the good clinician be without a well-stocked surgery?

“My growing conviction that the meat-heavy American diet and our increasing dependence on prepared and processed foods is detrimental not only to our personal health but to that of the planet has had an impact on my life.”

A nutshell of sound dietary advice, one every practicing clinician should take to heart.

Bittman concludes: “What I see as the continuing attack on good, sound eating and traditional farming in the United States is a political issue.”

What I see as the continuing attack on good sound traditional medical practice has lately become a political issue as well.