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“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.

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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.


Did The APA Miss A Defining Moment?

April 1, 2012

Sometimes an organization or individual facing a potential public-relations disaster can use the incident as a way to send a powerful message, as well as change the way that organization or individual is perceived.   I wonder whether the American Psychiatric Association (APA) may have missed its opportunity to do exactly that.

Several weeks ago, the CBS news program 60 Minutes ran a story with the provocative argument that antidepressants are no better than placebo.  Reporter Lesley Stahl highlighted the work of Irving Kirsch, a psychologist who has studied the placebo effect for decades.  He has concluded that most, and maybe all, of the benefit of antidepressants can be attributed to placebo.  Simply put, they work because patients (and their doctors) expect them to work.

Since then, the psychiatric establishment has offered several counterarguments.  All have placed psychiatry squarely on the defensive.  One psychiatrist (Michael Thase), interviewed on the CBS program, defended antidepressants, arguing that Kirsch “is confusing the results of studies with what goes on in practice.”  Alan Schatzberg, past APA president and former Stanford chairman, said at a conference last weekend (where he spoke about “new antidepressants”) that the APA executive committee was “outraged” at the story, glibly remarking, “In this nation, if you can attack a psychiatrist, you win a medal.”  The leadership of the APA has mounted an aggressive defense, too.  Incoming APA president and Columbia chairman Jeffrey Lieberman called Kirsch “mistaken and confused, … ideologically based, [and] … just plain wrong.”  Similarly, current APA president John Oldham called the story “irresponsible and dangerous [and] … at odds with common clinical experience.”

These are indeed strong words.  But it raises one very important question:  who or what exactly are these spokesmen defending?  Patients?  Psychiatrists?  Drugs?  It would seem to me that the leadership of a professional medical organization should be defending good patient care, or at the very least, greater opportunities for its members to provide good patient care.  The arguments put forth by APA leadership, however, seem to be defending none of the above.  Instead, they seem to be defending antidepressants.

For the purposes of this post, I won’t weigh in on the question of whether antidepressants work or not.  It’s a complicated issue with no easy answer (we’ll offer some insight in the May issue of the Carlat Psychiatry Report).  However, let’s just assume that the general public now has good reason to believe that current antidepressants are essentially worthless, thanks to the 60 Minutes story (not to mention—just a few weeks earlier—a report on NPR’s “Morning Edition,” as well as a two-part series by Marcia Angell in the New York Review of Books last summer).  Justifiably or not, our patients will be skeptical of psychopharmacology going forward.  If we psychiatrists are hell-bent on defending antidepressants, we’d better have even stronger reasons for doing so than simply “we know they work.”

But why are psychiatrists defending antidepressants in the first place?  If anyone should be defending antidepressants, it should be the drug companies, not psychiatrists.  Why didn’t 60 Minutes interview a Lilly medical expert to explain how they did the initial studies of Prozac, or a Pfizer scientist to explain why patients should be put on Pristiq?  (Now that would have been fun!!)  I would have loved to hear Michael Thase—or anyone from the psychiatric establishment—say to Lesley Stahl:

“You know, Dr. Kirsch might just be onto something.  His research is telling us that maybe antidepressants really don’t work as well as we once thought.  As a result, we psychiatrists want drug companies to do better studies on their drugs before approval, and stop marketing their drugs so aggressively to us—and to our patients—until they can show us better data.  In the meantime we want to get paid to provide therapy along with—or instead of—medications, and we hope that the APA puts more of an emphasis on non-biological treatments for depression in the future.”

Wouldn’t that have been great?  For those of us (like me) who think the essence of depression is far more than faulty biology to be corrected with a pill, it would have been very refreshing to hear.  Moreover, it would help our field to reclaim some of the “territory” we’ve been abdicating to others (therapists, psychologists, social workers)—territory that may ultimately be shown to be more relevant for most patients than drugs.  (By the way, I don’t mean to drive a wedge between psychiatry and these other specialties, as I truly believe we can coexist and complement each other.  But as I wrote in my last post, psychiatry really needs to stand up for something, and this would have been a perfect opportunity to do exactly that.)

To his credit, Dr. Oldham wrote an editorial two weeks ago in Psychiatric News (the APA’s weekly newsletter) explaining that he was asked to contribute to the 60 Minutes piece, but CBS canceled his interview at the last minute.  He wrote a response but CBS refused to post it on its website (the official APA response can be found here).  Interestingly, he went on to acknowledge that “good care” (i.e., whatever works) is what our patients need, and also conceded that, at least for “milder forms of depression,” the “nonspecific [placebo] effect dwarfs the specific [drug] effect.”

I think the APA would have a pretty powerful argument if it emphasized this message (i.e., that the placebo effect might be much greater than we believe, and that we should study this more closely—maybe even harness it for the sake of our patients) over what sounds like a knee-jerk defense of drugs.  It’s a message that would demand better science, prioritize our patients’ well-being, and, perhaps even reduce treatment costs in the long run.  If, instead, we call “foul” on anyone who criticizes medications, not only do we send the message that we put our faith in only one form of therapy (out of many), but we also become de facto spokespersons for the pharmaceutical industry.  If the APA wants to change that perception among the general public, this would be a great place to start.


The Problem With Organized Psychiatry

March 27, 2012

Well, it happened again.  I attended yet another professional conference this weekend (specifically, the annual meeting of my regional psychiatric society), and—along with all the talks, exhibits, and networking opportunities—came the call I’ve heard over and over again in venues like this one:  We must get psychiatrists involved in organized medicine.  We must stand up for what’s important to our profession and make our voices heard!!

Is this just a way for the organization to make money?  One would be forgiven for drawing this conclusion.  Annual dues are not trivial: membership in the society costs up to $290 per person, and also requires APA membership, which ranges from $205 to $565 per year.  But setting the money aside, the society firmly believes that we must protect ourselves and our profession.  Furthermore, the best way to do so is to recruit as many members as possible, and encourage members to stand up for our interests.

This raises one important question:  what exactly are we standing up for?  I think most psychiatrists would agree that we’d like to keep our jobs, and we’d like to get paid well, too.  (Oh, and benefits would be nice.)  But that’s about all the common ground that comes to mind.  The fact that we work in so many different settings makes it impossible for us to speak as a single voice or even (gasp!) to unionize.

Consider the following:  the conference featured a panel discussion by five early-career psychiatrists:  an academic psychiatrist; a county mental health psychiatrist; a jail psychiatrist; an HMO psychiatrist; and a cash-only private-practice psychiatrist.  What might all of those psychiatrists have in common?  As it turns out, not much.  The HMO psychiatrist has a 9-to-5 job, a stable income, and extraordinary benefits, but a restricted range of services, a very limited medication formulary and not much flexibility in what she can provide.  The private-practice guy, on the other hand, can do (and charge) essentially whatever he wants (a lot, as it turns out); but he also has to pay his own overhead.  The county psychiatrist wants his patients to have access to additional services (therapy, case management, housing, vocational training, etc) that might be irrelevant—or wasteful—in other settings.  The academic psychiatrist is concerned about his ability to obtain research funding, to keep his inpatient unit afloat, and to satisfy his department chair.  The jail psychiatrist wants access to substance abuse treatment and other vital services, and to help inmates make the transition back into their community safely.

Even within a given practice setting, different psychiatrists might disagree on what they want:  Some might want to see more patients, while delegating services like psychotherapy and case management to other providers.  On the other hand, some might want to spend more time with fewer patients and to be paid to provide these services themselves.  Some might want a more generous medication formulary, while others might argue that the benefits of medication are too exaggerated and want patients to have access to other types of treatment.  Finally, some might lobby for greater access to pharmaceutical companies and the benefits they provide (samples, coupons, lectures, meals, etc), while others might argue that pharmaceutical promotion has corrupted our field.

For most of the history of modern medicine, doctors have had a hard time “organizing” because there has been no entity worth organizing against.  Today, we have some definite targets: the Affordable Care Act, big insurance companies, hospital employers, pharmacy benefits managers, state and local governments, malpractice attorneys, etc.  But not all doctors see those threats equally.  (Many, in fact, welcome the Affordable Care Act with open arms.)  So even though there are, for instance, several unanswered questions as to how the ACA (aka “Obamacare”) might change the health-care-delivery landscape, the ramifications are, in the eyes of most doctors, too far-removed from the day-to-day aspects of patient care for any of us to worry about.  Just like everything else in the above list, we shrug them off as nuisances—the costs of doing business—and try to devote attention to our patients instead of agitating for change.

In psychiatry, the conflicts are particularly  wide-ranging, and the stakes more poorly defined than elsewhere in medicine, making the targets of our discontent less clear.  One of the panelists put it best when she said: “there’s a lot of white noise in psychiatry.”  In other words, we really can’t figure out where we’re headed—or even where we want to head.  At one extreme, for instance, are those psychiatrists who argue (sometimes convincingly) that all psychiatry is a farce, that diagnoses are socially constructed entities with no external validity, and that “treatment” produces more harm than good.  At the other extreme are the DSM promoters and their ilk, arguing for greater access to effective treatment, the medicalization of human behavior, and the early recognition and treatment of mental illness—sometimes even before it develops.

Until we psychiatrists determine what we want the future of psychiatric care to look like, it will be difficult for us to jump on any common bandwagon.  In the meantime, the future of our field will be determined by those who do have a well-formed agenda and who can rally around a common goal.  At present, that includes the APA, insurance companies, Big Pharma, and government.  As for the rest of us, we’ll just pick up whatever scraps are left over, and “organize” after we’ve finished our charts, returned our calls, completed the prior authorizations, filed the disability paperwork, paid our bills, and said good-night to our kids.


The Mythology of “Treatment-Resistant” Depression

February 27, 2011

“Treatment-resistant depression” is one of those clinical terms that has always been a bit unsettling to me.  Maybe I’m a pessimist, but when I hear this phrase, it reminds me that despite all the time, energy, and expense we have invested in understanding this all-too-common disease, we still have a long way to go.  Perhaps more troubling, the phrase also suggests an air of resignation or abandonment:  “We’ve tried everything, but you’re resistant to treatment, and there’s not much more we can do for you.”

But “everything” is a loaded term, and “treatment” takes many forms.  The term “treatment-resistant depression” first appeared in the literature in 1974 and has been used widely in the literature.  (Incidentally, despite appearing over 20 times in the APA’s 2010 revised treatment guidelines for major depression, it is never actually defined.)  The phrase is often used to describe patients who have failed to respond to a certain number of antidepressant trials (typically two, each from a different class), each of a reasonable (6-12 week) duration, although many other definitions have emerged over the years.

Failure to respond to “adequate” trials of appropriate antidepressant medications does indeed suggest that a patient is resistant to those treatments, and the clinician should think of other ways to approach that patient’s condition.  In today’s psychiatric practice, however, “treatment-resistant” is often a code word for simply adding another medication (like an atypical antipsychotic) or to consider somatic treatment options (such as electroconvulsive therapy, ECT, or transcranial magnetic stimulation, TMS).

Seen this way, it’s a fairly narrow view of “treatment.”  The psychiatric literature—not to mention years and years of anecdotal data—suggests that a broad range of interventions can be helpful in the management of depression, such as exercise, dietary supplements, mindfulness meditation, acupuncture, light therapy, and literally dozens of different psychotherapeutic approaches.  Call me obsessive, or pedantic, but to label someone’s depression as “treatment resistant” without an adequate trial of all of these approaches, seems premature at best, and fatalistic at worst.

What if we referred to someone’s weight problem as “diet-resistant obesity”?  Sure, there are myriad “diets” out there, and some obese individuals have tried several and simply don’t lose weight.  But perhaps these patients simply haven’t found the right one for their psychological/endocrine makeup and motivational level; there are also some genetic and biochemical causes of obesity that prevent weight loss regardless of diet.  If we label someone as “diet-resistant” it means that we may overlook some diets that would work, or ignore other ways of managing this condition.

Back to depression.   I recognize there’s not much of an evidence base for many of the potentially hundreds of different “cures” for depression in the popular and scientific literature.  And it would take far too much time to try them all.  Experienced clinicians will have seen plenty of examples of good antidepressant response to lithium, thyroid hormone, antipsychotics (such as Abilify), and somatic interventions like ECT.  But they have also seen failures with the exact same agents.

Unfortunately, our “decision tree” for assigning patients to different treatments is more like a dartboard than an evidence-based flowchart.  “Well, you’ve failed an SSRI and an SNRI, so let’s try an atypical,” goes the typical dialogue (not to mention the typical TV commercial or magazine ad), when we really should be trying to understand our patients at a deeper level in order to determine the ideal therapy for them.

Nevertheless, the “step therapy” requirements of insurance companies, as well as the large multicenter NIH-sponsored trials (like the STAR*D trial) which primarily focus on medications (yes, I am aware that STAR*D had a cognitive therapy component, although this has received little attention and was not widely chosen by study participants), continue to bias the clinician and patient in the direction of looking for the next pill or the next biological intervention, instead of thinking about patients as individuals with biological, genetic, psychological, and social determinants of their conditions.

Because in the long run, nobody is “treatment resistant,” they’re just resistant to what we’re currently offering them.


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