The Evidence of the Anecdote

June 8, 2012

The foundation of medical decision-making is “evidence-based medicine.”  As most readers know, this is the effort to use the best available evidence (using the scientific method) to make decisions and recommendations about how to treat individual patients.  “Evidence” is typically rated on four levels (1 to 4).  Level 1 represents high-quality evidence—usually the results of randomized clinical trials—while level 4 typically consists of case studies, uncontrolled observations, and anecdotal reports.

Clinical guidelines and drug approvals typically rely more heavily (or even exclusively) on level-1 evidence.  It is thought to be more valid, more authoritative, and less affected by variations among individuals.  For example, knowing that an antidepressant works (i.e., it gives a “statistically significant effect” vs placebo) in a large, controlled trial is more convincing to the average prescriber than knowing that it worked for a single depressed guy in Peoria.

But is it, really?  Not always (especially if you’re the one treating that depressed guy in Peoria).  Clinical trials can be misleading, even if their results are “significant.”  As most readers know, some investigators, after analyzing data from large industry-funded clinical trials, have concluded that antidepressants may not be effective at all—a story that has received extensive media coverage.  But lots of individuals insist that they do work, based on personal experience.  One such depression sufferer—who benefited greatly from antidepressants—wrote a recent post on the Atlantic Online, and quoted Peter Kramer: “to give the impression that [antidepressants] are placebos is to cause needless suffering” because many people do benefit from them.  Jonathan Leo, on the other hand, argues that this is a patently anti-scientific stance.  In a post this week on the website Mad In America, Leo points out (correctly) that there are people out there who will give recommendations and anecdotes in support of just about anything.  That doesn’t mean they work.

Both sides make some very good points.  We just need to find a way to reconcile them—i.e., to make the “science” more reflective of real-world cases, and use the wisdom of individual cases to influence our practice in a more scientifically valid way.  This is much easier said than done.

While psychiatrists often refer to the “art” of psychopharmacology, make no mistake:  they (we) take great pride in the fact that it’s supposedly grounded in hard science.  Drug doses, mechanisms, metabolites, serum levels, binding coefficients, polymorphisms, biomarkers, quantitative outcome measures—these are the calling cards of scientific investigation.  But when medications don’t work as planned (which is often), we improvise, and when we do, we quickly enter the world of personal experience and anecdote.  In fact, in the absence of objective disease markers (which we may never find, frankly), psychiatric treatment is built almost exclusively on anecdotes.  When a patient says a drug “worked” in some way that the data don’t support, or they experience a side effect that’s not listed in the PDR, that becomes the truth, and it happens far more frequently than we like to admit.

It’s even more apparent in psychotherapy.  When a therapist asks a question like “What went through your mind when that woman rejected you?” the number of possible responses is infinite, unlike a serum lithium level or a blood pressure.  A good therapist follows the patient’s story and individualizes treatment based on the individual case (and only loosely on some theory or therapeutic modality).  The “proof” is the outcome with that particular patient.  Sure, the “N” is only 1, but it’s the only one that counts.

Is there any way to make the science look more like the anecdotal evidence we actually see in practice?  I think not.  Most of us don’t even stop to think about how UN-convincing the “evidence” truly is.  In his book Pharmageddon, David Healy describes the example of the parachute:  no one needs to do a randomized, controlled trial to show that a parachute works.  It just does.   By comparison, to show that antidepressants “work,” drug companies must perform large, expensive trials (and often multiple trials at that) and even then, prove their results through statistical measures or clever trial designs.  Given this complexity, it’s a wonder that we believe clinical trials at all.

On the other side of the coin, there’s really no way to subject the anecdotal report, or case study, to the scientific method.  By definition, including more patients and controls (i.e., increasing the “N”) automatically introduces heterogeneity.  Whatever factor(s) led a particular patient to respond to Paxil “overnight” or to develop a harsh cough on Abilify are probably unique to that individual.

But maybe we can start looking at anecdotes through a scientific lens.  When we observe a particular response or effect, we ought to look not just at the most obvious cause (e.g., a new medication) but at the context in which it occurred, and entertain any and all alternative hypotheses.  Similarly, when planning treatment, we need to think not just about FDA-approved drugs, but also patient expectations, treatment setting, home environment, costs, other comorbidities, the availability of alternative therapies, and other data points or “independent variables.”  To use a crude but common analogy, it is indeed true that every person becomes his or her own laboratory, and should be viewed as such.

The more we look at patients this way, the further we get from clinical trials and the less relevant clinical trials become.  This is unfortunate, because—for better or for worse (I would vote for “worse”)—clinical trials have become the cornerstone of evidence-based psychiatry.  But a re-emphasis on anecdotes and individual cases is important.  Because in the end, it’s the individual who counts.  The individual resembles an N of 1 much more closely than he or she resembles an N of 200, and that’s probably the most important evidence we need to keep in mind.

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“Patient-Centered” Care and the Science of Psychiatry

May 30, 2012

When asked what makes for good patient care in medicine, a typical answer is that it should be “patient-centered.”  Sure, “evidence-based medicine” and expert clinical guidelines are helpful, but they only serve as the scientific foundation upon which we base our individualized treatment decisions.  What’s more important is how a disorder manifests in the patient and the treatments he or she is most likely to respond to (based on genetics, family history, biomarkers, etc).  In psychiatry, there’s the additional need to target treatment to the patient’s unique situation and context—always founded upon our scientific understanding of mental illness.

It’s almost a cliché to say that “no two people with depression [or bipolar or schizophrenia or whatever] are the same.”  But when the “same” disorder manifests differently in different people, isn’t it also possible that the disorders themselves are different?  Not only does such a question have implications for how we treat each individual, it also impacts how we interpret the “evidence,” how we use treatment guidelines, and what our diagnoses mean in the first place.

For starters, every patient wants something different.  What he or she gets is usually what the clinician wants, which, in turn, is determined by the diagnosis and established treatment guidelines:  lifelong medication treatment, referral for therapy, forced inpatient hospitalization, etc.  Obviously, our ultimate goal is to eliminate suffering by relieving one’s symptoms, but shouldn’t the route we take to get there reflect the patient’s desires?  When a patient gets what he or she wants, shouldn’t this count as good patient care, regardless of what the guidelines say?

For instance, some patients just want a quick fix (e.g., a pill, ideally without frequent office visits), because they have only a limited amount of money (or time) they’re willing to use for treatment.  Some patients need to complete “treatment” to satisfy a judge, an employer, or a family member.  Some patients visit the office simply to get a disability form filled out or satisfy some other social-service need.  Some simply want a place to vent, or to hear from a trusted professional that they’re “okay.”  Still others seek intensive, long-term therapy even when it’s not medically justified.  Patients request all sorts of things, which often differ from what the guidelines say they need.

Sometimes these requests are entirely reasonable, cost-effective, and practical.  But we psychiatrists often feel a need to practice evidence- (i.e., science-) based medicine; thus, we take treatment guidelines (and diagnoses) and try to make them apply to our patients, even when we know they want—or need—something else entirely, or won’t be able to follow through on our recommendations.  We prescribe medications even though we know the patient won’t be able to obtain the necessary lab monitoring; or we refer a patient for intensive therapy even though we know their insurance will only cover a handful of visits; we admit a suicidal patient to a locked inpatient ward even though we know the unpredictability of that environment may cause further distress; or we advise a child with ADHD and his family to undergo long-term behavioral therapy in conjunction with stimulants, when we know this resource may be unavailable.

Guidelines and diagnoses are written by committee, and, as such, rarely apply to the specifics of any individual patient.  Thus, a good clinician uses a clinical guideline simply as a tool—a reference point—to provide a foundation for an individual’s care, just as a master chef knows a basic recipe but alters it according to the tastes he wishes to bring out or which ingredients are in season.  A good clinician works outside the available guidelines for many practical reasons, not the least of which is the patient’s own belief system—what he or she thinks is wrong and how to fix it.  The same could be said for diagnoses themselves.  In truth, what’s written in the DSM is a model—a “case study,” if you will—by which real-world patients are observed and compared.  No patient ever fits a single diagnosis to a “T.”

Unfortunately, under the pressures of limited time, scarce resources, and the threat of legal action for a poor outcome, clinicians are more inclined to see patients for what they are than for who they are, and therefore adhere to guidelines even more closely than they’d like.  This corrupts treatment in many ways.  Diagnoses are given out which don’t fit (e.g., “parity” diagnoses must be given in order to maintain reimbursement).  Treatment recommendations are made which are far too costly or complex for some patients to follow.  Services like disability benefits are maintained far beyond the period they’re needed (because diagnoses “stick”).  And tremendous resources are devoted to the ongoing treatment of patients who simply want (and would benefit from) only sporadic check-ins, or who, conversely, can afford ongoing care themselves.

The entire situation calls into question the value of treatment guidelines, as well as the validity of psychiatric diagnoses.  Our patients’ unique characteristics, needs, and preferences—i.e., what helps patients to become “well”—vary far more widely than the symptoms upon which official treatment guidelines were developed.  Similarly, what motivates a person to seek treatment differs so widely from person to person, implying vastly different etiologies.

To provide optimal care to a patient, care must indeed be “patient-centered.”  But truly patient-centered care must not only sidestep the DSM and established treatment guidelines, but also, frequently, ignore diagnoses and guidelines altogether.  What does this say about the validity, relevance, and applicability of the diagnoses and guidelines at our disposal?  And what does this say about psychiatry as a science?


Addiction Psychiatry and The New Medicine

May 21, 2012

I have always believed that addictive disorders can teach us valuable lessons about other psychiatric conditions and about human behavior in general.  Addictions obviously involve behavior patterns, learning and memory processes, social influences, disturbed emotions, and environmental complexities.  Successful treatment of addiction requires attention to all of these facets of the disorder, and the addict often describes the recovery process not simply as being relieved of an illness, but as enduring a transformative, life-changing experience.

“Addiction psychiatry” is the area of psychiatry devoted to the treatment of these complicated disorders.  Certain trends in addiction psychiatry, however, seem to mirror larger trends in psychiatry as  whole.  Their impact on the future treatment of addictive behavior has yet to be determined, so it would be good to evaluate these trends to determine whether we’re headed in a direction we truly want to go.

Neurobiology:  Addiction psychiatry—like the rest of psychiatry—is slowly abandoning the patient and is becoming a largely neuroscientific enterprise.  While it is absolutely true that neurobiology has something to do with the addict’s repetitive, self-destructive behavior, and “brain reward pathways” are clearly involved, these do not tell the whole story.  Addicts refer to “people, places, and things” as the triggers for drug and alcohol use, not “dopamine, nucleus accumbens, and frontal cortex.”  This isn’t an argument against the need to study the biology of addiction, but to keep due focus on other factors which may affect one’s biology.  Virtually the same thing could also be said for most of what we treat in psychiatry; a multitude of factors might explain the presence of symptoms, but we’ve adopted a bias to think strictly in terms of brain pathways.

Medications:  Researchers in the addiction field (not to mention drug companies) devote much of their effort to disxover medications to treat addictions.  While they may stumble upon some useful adjunctive therapies, a “magic bullet” for addiction will probably never be found.  Moreover, I fear that the promise of medication-based treatments may foster a different sort of “dependence” among patients.  At this year’s APA Annual Meeting, for instance, I frequently heard the phrase “addictions are like other psychiatric disorders and therefore require lifelong treatment” (a statement which, by the way, is probably incorrect on TWO counts).  They weren’t talking about lifelong attendance at AA meetings or relapse prevention strategies, but rather to the need to take Suboxone or methadone (or the next “miracle drug”) indefinitely to achieve successful recovery.  Thus, as with other psychiatric disorders– many of which might only need short-term interventions but usually result in chronic pharmacological management—the long-term management of addiction may not reside in the maintenance of a strong recovery program but in the taking of a pill.

New Providers:  Once a relatively unpopular subspecialty, addiction psychiatry is now a burgeoning field, thanks to this new focus on neurobiology and medication management—areas in which psychiatrists consider themselves well versed.  For example, a psychiatrist can become an “addiction psychiatrist” by receiving “Suboxone certification” (i.e., taking an 8-hour online course to obtain a special DEA license to prescribe buprenorphine, an opioid agonist).  I have nothing against Suboxone: patients who take daily Suboxone are far less likely to use opioids, more likely to remain in treatment, and less likely to suffer the consequences of opioid abuse.  In fact, one might argue that the effectiveness of Suboxone—and methadone, for that matter—for opioid dependence is far greater than that of SSRIs in the treatment of depression.  Many Suboxone prescribers, however, have little exposure to the psychosocial aspects—and hard work—involved in fully treating (or overcoming) an addiction, and a pill is simply a substitute for opioids (which itself can be abused).  Nevertheless, prescribing a medication at monthly intervals—sometimes with little discussion about progress toward other recovery goals—resembles everything else we do in psychiatry; it’s no wonder that we’re drawn to it.

Patients:  Like many patients who seek psychiatric help, addicts might start to see “recovery” as a simple matter of making an appointment with a doctor and getting a prescription.  To be sure, many patients have used drugs like Suboxone or methadone to help them overcome deadly addictions, just as some individuals with major depression owe their lives to SSRIs or ECT.  But others have been genuinely hurt by these drugs.  Patients who have successfully discontinued Suboxone often say that it was the most difficult drug to stop—worse than any other opioid they had abused in the past.  Patients should always be reminded of the potential risks and dangers of treatment.  More importantly, we providers have an obligation to make patients aware of other ways of achieving sobriety and when to use them.  Strategies that don’t rely so heavily on the medical model might require a lot more work, but the payoffs may be much greater.

——

Addictions involve complex biological, psychological, and social dimensions that differ from person to person.  The response of the psychiatric profession has been to devote more research to the neurobiology of addictions and the development of anti-addiction drugs, potentially at the expense of exploring other aspects that may be more promising.  As expected, psychiatrists, pharmaceutical companies, third-party payers, and the general public are quickly buying into this model.

Psychiatry finds itself in a Catch-22.  On the one hand, psychiatry is often criticized for not being “medical,” and focusing on the biology of addiction is a good way to adhere to the medical model (and, perhaps, lead us to better pharmacotherapies).  On the other hand, psychiatric disorders—and especially addictions—are multifactorial in nature, and successful treatment often requires a comprehensive approach.  Fortunately, it may not yet be too late for psychiatry to retreat from a full-scale embrace of the medical model.  Putting the patient first sometimes means stepping away from the science.  And as difficult and non-intuitive as that may be, sometimes that’s where the healthiest recovery can be found.


“Trainwrecks”

May 15, 2012

One of the highlights of the American Psychiatric Association (APA) Annual Meeting is the Exhibit Hall.  Here, under bright lights and fancy multimedia displays, sponsors get to show off their new wares.  If anyone wonders whether modern psychiatry isn’t all about psychopharmacology, one visit to the APA Exhibit Hall would set them straight.  Far and away, the biggest and glitziest displays are those of Big Pharma, promising satisfaction and success—and legions of grateful patients—for prescribing their products.

At the 2012 Annual Meeting last week, I checked out most of the Pharma exhibits, mainly just to see what was in the pipeline.  (Not much, it turns out.)  I didn’t partake in any of the refreshments—lest I be reported to the Feds as the recipient of a $2 cappuccino or a $4 smoothie—but still felt somewhat like an awestruck Charlie Bucket in Willie Wonka’s miraculous Chocolate Factory.

One memorable exchange was at the Nuedexta booth.  Nuedexta, as readers of this blog may recall from a 2011 post, is a combination of dextromethorphan and quinidine, sold by Avanir Pharmaceuticals and approved for the treatment of “pseudobulbar affect,” or PBA.  PBA is a neurological condition, found in patients with multiple sclerosis or stroke, and characterized by uncontrollable laughing and crying.  While PBA can be a devastating condition, treatment options do exist.  In my blog post I wrote that “a number of medications, including SSRIs like citalopram, and tricyclic antidepressants (TCAs), are effective in managing the symptoms of PBA.”  One year later, Nuedexta still has not been approved by the FDA for any other indication than PBA.

In my discussion with the Avanir salesman, I asked the same question I posed to the Avanir rep one year ago:  “If I had a patient in whom I suspected PBA, I’d probably refer him to his neurologist for management of that condition—so why, as a psychiatrist, would I use this medication?”  The rep’s answer, delivered in that cool, convincing way that can only emerge from the salesman’s anima, was a disturbing insight into the practice of psychiatry in the 21st century:

“Well, you probably have some patients who are real trainwrecks, with ten things going on.  Chances are, there might be some PBA in there, so why not try some Nuedexta and see if it makes a difference?”

I nodded, thanked him, and politely excused myself.  (I also promptly tweeted about the exchange.)  I don’t know if his words comprised an official Nuedexta sales pitch, but the ease with which he shared it (no wink-wink, nudge-nudge here) suggested that it has proven successful in the past.  Quite frankly, it’s also somewhat ugly.

First of all, I refuse to refer to any of my patients as “trainwrecks.”  Doctors and medical students sometimes use this term to refer to patients with multiple problems and who, as a result, are difficult to care for.  We’ve all used it, myself included.  But the more I empathize with my patients and try to understand their unique needs and wishes, the more I realize how condescending it is.  (Some might refer to me as a “trainwreck,” too, given certain aspects of my past.)  Furthermore, many of the patients with this label have probably—and unfortunately—earned it as a direct result of psychiatric “treatment.”

Secondly, as any good scientist will tell you, the way to figure out the inner workings of a complicated system is to take it apart and analyze its core features.  If a person presents an unclear diagnostic picture, clouded by a half-dozen medications and no clear treatment goals, the best approach is to take things away and see what remains, not to add something else to the mix and “see if it makes a difference.”

Third, the words of the Avanir rep demonstrate precisely what is wrong with our modern era of biological psychopharmacology.  Because the syndromes and “disorders” we treat are so vague, and because many symptoms can be found in multiple conditions—not to mention everyday life—virtually anything a patient reports could be construed as an indication for a drug, with a neurobiological mechanism to “explain” it.  This is, of course, exactly what I predicted for Nuedexta when I referred to it as a “pipeline in a pill” (a phrase that originally came from Avanir’s CEO).  But the same could be said for just about any drug a psychiatrist prescribes for an “emotional” or “behavioral” problem.  When ordinary complaints can be explained by tenuous biological pathways, it becomes far easier to rationalize the use of a drug, regardless of whether data exist to support it.

Finally, the strategy of “throw a medication into the mix and see if it works” is far too commonplace in psychiatry.  It is completely mindless and ignores any understanding of the underlying biology (if there is such a thing) of the illnesses we treat.  And yet it has become an accepted treatment paradigm.  Consider, for instance, the use of atypical antipsychotics in the treatment of depression.  Not only have the manufacturers of Abilify and Seroquel XR never explained how a dopamine partial agonist or antagonist (respectively) might help treat depression, but look at the way they use the results of STAR*D to help promote their products.  STAR*D, as you might recall, was a large-scale, multi-step study comparing multiple antidepressants which found that no single antidepressant was any better than any other.  (All were pretty poor, actually.)  The antipsychotic manufacturers want us to use their products not because they performed well in STAR*D (they weren’t even in STAR*D!!!) but because nothing else seemed to work very well.

If the most convincing argument we can make for a drug therapy is “well, nothing else has worked, so let’s try it,” this doesn’t bode well for the future of our field.  This strategy is mindless and sloppy, not to mention potentially dangerous.  It opens the floodgates for expensive and relatively unproven treatments which, in all fairness, may work in some patients, but add to the iatrogenic burden—and diagnostic confusion—of others.  It also permits Pharma (and the APA’s key opinion leaders) to maintain the false promise of a neurochemical solution for the human, personal suffering of those who seek our help.

This, in my opinion, is the real “trainwreck” that awaits modern psychiatry.  And only psychiatrists can keep us on the tracks.


Is The Joke On Me?

May 12, 2012

I recently returned from the American Psychiatric Association (APA) Annual Meeting in Philadelphia.  I had the pleasure of participating on a panel discussing “psychiatrists and the new media” with the bloggers/authors from Shrink Rap, and Bob Hsiung of dr-bob.org.  The panel discussion was a success.  Some other parts of the conference, however, left me with a sense of doubt and unease.  I enjoy being a psychiatrist, but whenever I attend these psychiatric meetings, I sometimes find myself questioning the nature of what I do.  At times I wonder whether everyone else knows something I don’t.  Sometimes I even ask myself:  is the joke on me?

Here’s an example of what I mean.  On Sunday, David Kupfer of the University of Pittsburgh (and task force chair of the forthcoming DSM-5) gave a talk on “Rethinking Bipolar Disorder.”  The room—a cavernous hall at the Pennsylvania Convention Center—was packed.  Every chair was filled, while scores of attendees stood in the back or sat on the floor, listening with rapt attention.  The talk itself was a discussion of “where we need to go” in the management of bipolar disorder in the future.  Dr Kupfer described a new view of bipolar disorder as a chronic, multifactorial disorder involving not just mood lability and extremes of behavior, but also endocrine, inflammatory, neurophysiologic, and metabolic processes that deserve our attention as well.  He emphasized the fact that in between mood episodes, and even before they develop, there are a range of “dysfunctional symptom domains”—involving emotions, cognition, sleep, physical symptoms, and others—that we psychiatrists should be aware of.  He also introduced a potential way to “stage” development of bipolar disorder (similar to the way doctors stage tumors), suggesting that people at early stages might benefit from prophylactic psychiatric intervention.

Basically, the take-home message (for me, at least) was that in the future, psychiatrists will be responsible for treating other manifestations of bipolar disorder than those we currently attend to.  We will also need to look for subthreshold symptoms in people who might have a “prodrome” of bipolar disorder.

A sympathetic observer might say that Kupfer is simply asking us to practice good medicine, caring for the entire person rather than one’s symptoms, and prevent development or recurrence of bipolar illness.  On the other hand, a cynic might look at these pronouncements as a sort of disease-mongering, encouraging us to uncover signs of “disease” where they might not exist.  But both of these conclusions overlook a much more fundamental question that, to me, remains unanswered.  What exactly is bipolar disorder anyway?

I realize that’s an extraordinarily embarrassing question for a psychiatrist to ask.  And in all fairness, I do know what bipolar disorder is (or, at least, what the textbooks and the DSM-IV say it is).  I have seen examples of manic episodes in my own practice, and in my personal life, and have seen how they respond to medications, psychotherapy, or the passage of time.  But those are the minority.  Over the years (although my career is still relatively young), I have also seen dozens, if not hundreds, of people given the diagnosis of “bipolar disorder” without a clear history of a manic episode—the defining feature of bipolar disorder, according to the DSM.

As I looked around the room at everyone concentrating on Dr Kupfer’s every word, I wondered to myself, am I the only one with this dilemma?  Are my patients “special” or “unique”?  Maybe I’m a bad psychiatrist; maybe I don’t ask the right questions.  Or maybe everyone else is playing a joke on me.   That’s unlikely; others do see the same sorts of patients I do (I know this for a fact, from my own discussions with other psychiatrists).  But nobody seems to have the same crisis of confidence that I do.  It makes me wonder whether we have reached a point in psychiatry when psychiatrists can listen to a talk like this one (or see patients each day) and accept diagnostic categories, without paying any attention to the fact that they our nosology says virtually nothing at all about the unique nature of each person’s suffering.  It seems that we accept the words of our authority figures without asking the fundamental question of whether they have any basis in reality.  Or maybe I’m just missing out on the joke.

As far as I’m concerned, no two “bipolar” patients are alike, and no two “bipolar” patients have the same treatment goals.  The same can be said for almost everything else we treat, from “depression” to “borderline personality disorder” to addiction.  In my opinion, lumping all those people together and assuming they’re all alike for the purposes of a talk (or, even worse, for a clinical trial) makes it difficult—and quite foolish—to draw any conclusions about that group of individuals.

What we need to do is to figure out whether what we call “bipolar disorder” is a true disorder in the first place, rather than accept it uncritically and start looking for yet additional symptom domains or biomarkers as new targets of treatment.  To accept the assumption that everyone currently with the “bipolar” label indeed has the same disorder (or any disorder at all) makes a mockery of the diagnostic process and destroys the meaning of the word.  Some would argue this has already happened.

But then again, maybe I’m the only one who sees it this way.  No one at Kupfer’s talk seemed to demonstrate any bewilderment or concern that we might be heading towards a new era of disease management without really knowing what “disease” we’re treating in the first place.  If this is the case, I sure would appreciate it if someone would let me in on the joke.


What’s the Proper Place of Science in Psychiatry and Medicine?

April 29, 2012

On the pages of this blog I have frequently written about the “scientific” aspects of psychiatry and questioned how truly scientific they are.   And I’m certainly not alone.  With the growing outcry against psychiatry for its medicalization of human behavior and the use of powerful drugs to treat what’s essentially normal variability in our everyday existence, it seems as if everyone is challenging the evidence base behind what we do—except most of us who do it on a daily basis.

Psychiatrists are unique among medical professionals, because we need to play two roles at once.  On the one hand, we must be scientists—determining whether there’s a biological basis for a patient’s symptoms.  On the other hand, we must identify environmental or psychological precursors to a patient’s complaints and help to “fix” those, too.  However, today’s psychiatrists often eschew the latter approach, brushing off their patients’ internal or interpersonal dynamics and ignoring environmental and social influences, rushing instead to play the “doctor” card:  labeling, diagnosing, and prescribing.

Why do we do this?  We all know the obvious reasons:  shrinking appointment lengths, the influence of drug companies, psychiatrists’ increasing desire to see themselves as “clinical neuroscientists,” and so on.

But there’s another, less obvious reason, one which affects all doctors.  Medical training is all about science.  There’s a reason why pre-meds have to take a year of calculus, organic chemistry, and physics to get into medical school.  It’s not because doctors solve differential equations and perform redox reactions all day.  It’s because medicine is a science (or so we tell ourselves), and, as such, we demand a scientific, mechanistic explanation for everything from a broken toe to a myocardial infarction to a manic episode.  We do “med checks,” as much as we might not want to, because that’s what we’ve been trained to do.  And the same holds true for other medical specialties, too.  Little emphasis is placed on talking and listening.  Instead, it’s all about data, numbers, mechanisms, outcomes, and the right drugs for the job.

Perhaps it’s time to rethink the whole “medical science” enterprise.  In much of medicine, paying more and more attention to biological measures—and the scientific evidence—hasn’t really improved outcomes.  “Evidence-based medicine,” in fact, is really just a way for payers and the government to create guidelines to reduce costs, not a way to improve individual patients’ care. Moreover, we see examples all the time—in all medical disciplines—of the corruption of scientific data (often fueled by drug company greed) and very little improvement in patient outcomes.  Statins, for instance, are effective drugs for high cholesterol, but their widespread use in people with no other risk factors seems to confer no additional benefit.  Decades of research into understanding appetite and metabolism hasn’t eradicated obesity in our society.  A full-scale effort to elucidate the brain’s “reward pathways” hasn’t made a dent in the prevalence of drug and alcohol addiction.

Psychiatry suffers under the same scientific determinism.  Everything we call a “disease” in psychiatry could just as easily be called something else.  I’ve seen lots of depressed people in my office, but I can’t say for sure whether I’ve ever seen one with a biological illness called “Major Depressive Disorder.”  But that’s what I write in the chart.  If a patient in my med-management clinic tells me he feels better after six weeks on an antidepressant, I have no way of knowing whether it was due to the drug.  But that’s what I tell myself—and that’s usually what he believes, too.  My training encourages me to see my patients as objects, as collections of symptoms, and to interpret my “biological” interventions as having a far greater impact on my patients’ health than the hundreds or thousands of other phenomena my patient experiences in between appointments with me.  Is this fair?

(This may explain some of the extreme animosity from the anti-psychiatry crowd—and others—against some very well-meaning psychiatrists.  With few exceptions, the psychiatrists I know are thoughtful, compassionate people who entered this field with a true desire to alleviate suffering.  Unfortunately, by virtue of their training, many have become uncritical supporters the scientific model, making them easy targets for those who have been hurt by that very same model.)

My colleague Daniel Carlat, in his book Unhinged, asks the question: “Why do [psychiatrists] go to medical school? How do months of intensive training in surgery, internal medicine, radiology, etc., help psychiatrists treat mental illness?”  He lays out several alternatives for the future of psychiatric training.  One option is a hybrid approach that combines a few years of biomedical training with a few years of rigorous exposure to psychological techniques and theories.  Whether this would be acceptable to psychiatrists—many of whom wear their MD degrees as scientific badges of honor—or to psychologists—who might feel that their turf is being threatened—is anyone’s guess.

I see yet another alternative.  Rather than taking future psychiatrists out of medical school and teaching them an abbreviated version of medicine, let’s change medical school itself.  Let’s take some of the science out of medicine and replace it with what really matters: learning how to think critically and communicate with patients (and each other), and to think about our patients in a greater societal context.  Soon the Medical College Admissions Test (MCAT) will include more questions about cultural studies and ethics.  Medical education should go one step further and offer more exposure to economics, politics, management, health-care policy, decision-making skills, communication techniques, multicultural issues, patient advocacy, and, of course, how to interpret and critique the science that does exist.

We doctors will need a scientific background to interpret the data we see on a regular basis, but we must also acknowledge that our day-to-day clinical work requires very little science at all.  (In fact, all the biochemistry, physiology, pharmacology, and anatomy we learned in medical school is either (a) irrelevant, or (b) readily available on our iPhones or by a quick search of Wikipedia.)  We need to be cautious not to bring science into a clinical scenario simply because it’s easy or “it’s what we know,” particularly—especially—when it provides no benefit to the patient.

So we don’t need to take psychiatry out of medicine.  Instead, we should bring a more enlightened, patient-centered approach to all of medicine, starting with formal medical training itself.  This would help all medical professionals to offer care that focuses on the person, rather than an MRI or CT scan, receptor profile or genetic polymorphism, or lab value or score on a checklist.  It would help us to be more accepting of our patients’ diversity and less likely to rush to a diagnosis.  It might even restore some respect for the psychiatric profession, both within and outside of medicine.  Sure, it might mean that fewer patients are labeled with “mental illnesses” (translating into less of a need for psychiatrists), but for the good of our patients—and for the future of our profession—it’s a sacrifice that we ought to be willing to make.


Depression Tests: When “Basic” Research Becomes “Applied”

April 22, 2012

Anyone with an understanding of the scientific process can appreciate the difference between “basic” and “applied” research.  Basic research, often considered “pure” science, is the study of science for its own sake, motivated by curiosity and a desire to understand.  General questions and theories are tested, often without any obvious practical application.  On the other hand, “applied” research is usually done for a specific reason: to solve a real-world problem or to develop a new product: a better mousetrap, a faster computer, or a more effective way to diagnose illness.

In psychiatric research, the distinction between “basic” and “applied” research is often blurred.  Two recent articles (and the accompanying media attention they’ve received) provide very good examples of this phenomenon.  Both stories involve blood tests to diagnose depression.  Both are intriguing, novel studies.  Both may revolutionize our understanding of mental illness.  But responses to both have also been blown way out of proportion, seeking to “apply” what is clearly only at the “basic” stage.

The first study, by George Papakostas and his colleagues at Massachusetts General Hospital and Ridge Diagnostics, was published last December in the journal Molecular Psychiatry.  They developed a technique to measure nine proteins in the blood, plug those values into a fancy (although proprietary—i.e., unknown) algorithm, and calculate an “MDDScore” which, supposedly, diagnoses depression.  In their paper, they compared 70 depressed patients with 43 non-depressed people and showed that their assay identifies depression with a specificity of 81% and a sensitivity of 91%.

The other study, published two weeks ago in Translational Psychiatry by Eve Redei and her colleagues at Northwestern University, purports to diagnose depression in adolescents.  They didn’t measure proteins in patients’ blood, but rather levels of RNA.  (As a quick aside, RNA is the “messenger” molecule inside each cell that tells the cell which proteins to make.)  They studied a smaller number of patients—only 14 depressed teenagers, compared with 14 non-depressed controls—and identified 11 RNA molecules which were expressed differently between the two groups.  These were selected from a much larger number of RNA transcripts on the basis of an animal model of depression: specifically, a rat strain that was bred to show “depressive-like” behavior.

If we look at each of these studies as “basic” science, they offer some potentially tantalizing insights into what might be happening in the bodies of depressed people (or rats).  Even though some of us argue that no two “depressed” people are alike—and we should look instead at person-centered factors that might explain how they are unique—these studies nevertheless might have something to say about the common underlying biology of depression—if such a thing exists.  At the very least, further investigation might explain why proteins that have no logical connection with depression (such as apolipoprotein CIII or myeloperoxidase) or RNA transcripts (for genes like toll-like-receptor-1 or S-phase-cyclin-A-associated protein) might help us, someday, to develop more effective treatments than the often ineffective SSRIs that are the current standard of care.

Surprisingly, though, this is not how these articles have been greeted.  Take the Redei article, for instance.  Since its publication, there have been dozens of media mentions, with such headlines as “Depression Blood Test for Teens May Lead To Less Stigma” and “Depression Researchers May Have Developed First Blood Test For Teens.”  To the everyday reader, it seems as if we’ve gone straight from the bench to the bedside.  Granted, each story mentions that the test is not quite “ready for prime time,” but headlines draw readers’ attention.  Even the APA’s official Twitter feed mentioned it (“Blood test for early-onset #depression promising,” along with the tags “#childrenshealth” and “#fightstigma”), giving it a certain degree of legitimacy among doctors and patients alike.

(I should point out that one of Redei’s co-authors, Bill Gardner, emphasized—correctly—on his own blog that their study was NOT to be seen as a test for depression, and that it required refinement and replication before it could be used clinically.  He also acknowledged that their study population—adolescents—are often targets for unnecessary pharmacological intervention, demanding even further caution in interpreting their results.)

As for the Papakostas article, there was a similar flurry of articles about it when preliminary results were presented last year.  Like Redei’s research, it’s an interesting study that could change the way we diagnose depression.  However, unlike Redei’s study, it was funded by a private, self-proclaimed “neurodiagnostics” company.  (That company, Ridge Diagnostics, has not revealed the algorithm by which they calculate their “MDDScore,” essentially preventing any independent group from trying to replicate their findings.)

Incidentally, the Chairman of the Board of Ridge Diagnostics is David Hale, who also founded—and is Chairman of—Somaxon Pharmaceuticals, a company I wrote about last year when it tried to bring low-dose doxepin to the market as a sleep aid, and then used its patent muscle to issue cease-and-desist letters to people who suggested using the ultra-cheap generic version instead of Somaxon’s name-brand drug.

Ridge Diagnostics has apparently decided not to wait for replication of its findings, and instead is taking its MDDScore to the masses, complete with a Twitter feed, a Facebook Page, and a series of videos selling the MDDScore (priced at a low, low $745!), aimed directly at patients.  At this rate, it’s only a matter of time before the MDDScore is featured on the “Dr Oz Show” or “The Doctors.”  Take a look at this professionally produced video, for instance, posted last month on Youtube:


(Interesting—the host hardly even mentions the word “depression.”  A focus group must have told them that it detracted from his sales pitch.)

I think it’s great that scientists are investigating the basic biology of depression.  I also have no problem when private companies try to get in on the act.  However, when research that is obviously at the “basic” stage (and, yes, not ready for prime time) becomes the focus of a viral video marketing campaign or a major story on the Huffington Post, one must wonder why we’ve been so quick to cross the line from “basic” research into the “applied” uses of those preliminary findings.  Okay, okay, I know the answer is money.  But who has the authority—and the voice—to say, “not so fast” and preserve some integrity in the field of psychiatric research?  Where’s the money in that?


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