Prove That You Need Me

December 11, 2011

I’ll confess, sometimes after I see a patient I ask myself, “was that really necessary??”  That’s not to suggest that the interaction was a complete waste of time, or that I regularly provide treatment that is excessive or harmful, but I am frequently reminded of an observation I first made many years ago:  we in psychiatry provide a lot of “care” that might be considered unnecessary and, in the long run, wasteful and inefficient.

(Note: I am specifically referring here to certain aspects of outpatient mental health treatment.  The same might occur in other medical specialties, but those aren’t my areas of expertise, so I can’t comment.  Furthermore, I am NOT referring to regular health-maintenance visits to one’s primary physician, pediatrician, or OB-GYN, in which the “care” consists of an examination and, if necessary, screening tests or preventive measures.)

Consider the following examples of wasteful, inefficient care in psychiatry.

I see many patients (particularly in the community setting) who have been “treated,” often irregularly and infrequently, by a variety of psychiatrists or other physicians who have doled out a half-dozen psychiatric diagnoses and a laundry list of medications.  When I see patients like these, their complaints are usually vague and nonspecific, adherence to past treatments has been questionable, and a substance-abuse component is often present.  While these patients may indeed suffer from mental illness (or, in many cases, simply face profound psychosocial stressors that the system allows us to call mental illness), it is unlikely that these patients will receive the resources they truly need from conventional psychiatric practice.  However, it’s convenient—for us as a society—to shunt them into the psychiatric juggernaut, where they often lose any hope for lasting recovery.

Another example is the patient living in difficult, stressful circumstances who is referred to a psychiatrist by a social service agency or by the criminal justice system “for an evaluation.”  Again, these individuals may face huge psychosocial stressors—and may indeed benefit from professional assistance of some sort—but psychiatric care?  It’s hard for a psychiatrist to say no.  Instead, we give a diagnosis, frequently an “NOS” diagnosis, which, in practice, means “he sort of looks like he might have depression or an anxiety disorder or psychosis, but we’re not sure yet.”  This may be justifiable at first, but unfortunately these diagnoses tend to stick—and, interestingly, patients are rarely undiagnosed—locking the patient into a neverending roller-coaster of medication trials and, not uncommonly, a lifetime of psychiatric “disability,” at great expense to all.

Finally, there are those individuals who see a psychiatrist at the urging of their primary doctor or a family member.  They may complain of very legitimate symptoms of irritability or mood lability, guilt or sadness over a recent loss, sleep disturbance or anxiety, or chaotic personal relationships—phenomena which we have all experienced to various degrees.  Sometimes these symptoms are incapacitating; sometimes not.  But we psychiatrists are good at making square pegs fit into round holes; through our DSM-tainted lenses, we give whatever diagnosis “fits best”—often the dreaded “NOS,” discussed above.  Furthermore, because many of us are loath to send a patient home empty-handed—and ill-prepared to do anything other than diagnose or prescribe— we give a medication which we think might “work.”  (And if it does, we see it as affirmation of our diagnosis, but that’s material for another post.)

These three situations are common in psychiatry.  I’m absolutely not saying that patients like these should be denied treatment, “shown the door,” and asked never to return.  As a mentor taught me many years ago, no one sees a psychiatrist when everything in his or her life is perfect.  But sometimes we fail to recognize that the psychiatrist may approach the patient and his or her complaints in the wrong way.

I believe that, when evaluating patients, psychiatrists should use the tools of scientific investigation:  an open mind (although we can use our past experience and intuition, as long as we search for data to support it, too), deep interest and curiosity, a systematic method of analysis, and, most importantly, the lack of bias or predetermined outcome.  A significant aspect of this “data collection” is an accurate assessment of the patient’s resources and ability to overcome his symptoms; if his resources can be augmented by psychotherapeutic intervention or by medication, fine, but if not (or if an accurate assessment of his strengths shows that such intervention is unnecessary), then we must have the willingness to say no and back out.

Let me emphasize once again, I am NOT saying that we should be skeptical of patients, or ignore their complaints.  But we need to acknowledge we are predisposed (as a result of our training, the nonspecificity of the DSM-IV, and the current treatment paradigm in psychiatry) to see “mental illness” where it may not exist, and prescribe drugs in response.  As a result, patients sometimes feel that their complaints “aren’t heard” or are “misunderstood.”  Alternatively (and worse, in my opinion), some patients may actually buy into the diagnosis (when in fact it may just be a figment of the doctor’s—or the APA’s—imagination) and use it as an excuse or a rationale for not taking other measures to engage in lifestyle change.  To provide truly compassionate and patient-centered care, we must act differently.

I know some psychiatrists will respond, “I always see my patients with an open mind, I’m fair and honest, and I give the patient the benefit of the doubt.”  Of course, there are exceptions, but as a product of psychiatric training within the last decade, I can attest to the fact that this approach is rare.

Psychiatrists are taught to look for pathology, not health.  And as they say, “seek and ye shall find.”

A more life-affirming and empowering strategy might be for the psychiatrist to (a) first evaluate a person’s strengths and assets, (b) carefully assess the patient’s goals or desires, (c) determine what prevents him or her from achieving those goals, and, most crucially, (d) determine whether the psychiatrist has the means to help the patient achieve those goals (not necessarily to “correct a symptom” or “treat a diagnosis”).  Then and only then can treatment commence.  Otherwise, we’re spinning our wheels, misleading our patients, wasting our time, and serving no one.

We Do Not Know What We Cannot Know

December 5, 2011

Who provides the best mental health care?  I’m not referring to the relative merits of psychiatrist vs. psychologist, academic center vs. private practice, or meds vs. therapy.  No, I’m referring to the actual individuals providing the treatment, and the background that they bring to the therapeutic interaction.  We like to talk about education and degrees, publications and professional designations, but to the patient, do these really count for anything?

Why do I ask?  Readers of this blog are aware that I do some part-time work in community mental health, and while I feel that I have a good rapport with most of my patients there, they couldn’t care less about where I went to school or how many publications are on my CV.  By the same token, I cannot relate with much of what they experience in their day-to-day lives.  The symptoms they report almost surely have a very different meaning to them, than the same symptoms would to me or to someone in my family.

I also work on an inpatient psychiatric unit where, again, we doctors are on a different plane than the patients we treat.  In fact, I’ve been impressed by the degree (and duration) of peer interaction, even in these acutely ill patients, and wonder whether this may be a significantly therapeutic component of their hospital stay.  I regularly see groups of two or three patients sitting together, discussing medications, family or relationship problems, legal issues, or—as I experienced just the other day—simply singing or dancing with each other.  It seems as if patients can trust their peers far more easily than their providers, who aren’t in their shoes.

And in the addiction field, “mutual support” (12-step meetings or other group therapy), in which the “therapeutic breakthroughs” come not from professional staff but from the influence of peers, provide the foundation of most of our treatment approaches.  Having had my own experiences as a patient, too, I can attest to the fact that my peers often “got” me far more effectively than those I was paying to do so.

Is this necessarily a problem?  After all, a surgeon doesn’t have to experience colon cancer to perform a bowel resection, an internist doesn’t need to be diagnosed with diabetes to understand its management, and a man can be an excellent obstetrician even though he’ll never give birth to a child.  Even in mental health, professionals can be quite astute and eminently capable, even without a history of mental illness themselves (even though we’re often accused by our colleagues as selecting this profession to cure our own problems!).

But it might be time to reevaluate this.  As a psychiatrist, I may understand the neuropharmacology of SSRIs and antipsychotics, the (supposed) biological basis of depression, and the foundations of cognitive behavior therapy more deeply than any of my patients, but in the long run, does any of this matter?  It’s bad enough that we lump together all sorts of symptoms as “major depression”; it gets infinitely more complex when we consider the vast range of circumstances that give rise to a person’s symptoms, and only the patient—or someone who shares the patient’s experience—can truly understand this.

Sometimes I feel like a fraud.  I’m expected to be objective and detached when, in fact, I’m dealing with subjective, emotional, and sometimes existential anguish that simply cannot be shared or felt by someone on my side of the couch (or desk, as it were).

How to remedy this?  For me, the best approach is not to view patients through the foggy and distorted lens of the DSM-IV, or with a narrow-minded focus on symptoms and medications, but rather to get to know them as I might wish to know a new friend.  I want to listen to their needs and desires, their intrinsic weaknesses and strengths (in a way, to not even see them as patients) and then provide whatever help or structure that they need—if I can.  Perhaps that type of engagement is not the standard of care, but patients seem to prefer it.

A very practical solution might be to rely on peer support more frequently than we do.  That is, ask patients to advise and connect with each other, rather than rely on ‘professionals’ like me.  (BTW, I’m not wishing my way out of a job; I truly believe that there will be a need for trained professionals to facilitate or oversee this process.)  We already know that the most effective non-pharmacological treatments for mental illness (e.g., the Soteria project) rely heavily on peer support.  The rise of social media has also empowered patients like never before.  Some of the most insightful (and respectful) information I have learned in this field comes from patient-oriented websites like Surviving Antidepressants, Beyond Meds, Holistic Recovery from Schizophrenia, and many others.  (In fact, I think it’s incumbent upon doctors to pay close attention to what’s written on sites like these—because these are the people who ask for our help!)

But maybe the most important thing we can do as professionals is to heed the advice shared by our patients and peers in the recovery community, which is to practice humility in our daily affairs.  We must acknowledge what we do not know.  And the most important information we do not have is what it’s like to spend a day in our patients’ shoes.  While we can share our expert knowledge with patients—and sometimes order treatments with which our patients disagree—we must ultimately respect the fact that our patients know themselves—and others like them—far greater than we do.

I Really Need To Lighten Up

December 1, 2011

Reading back over my last few blog posts, I realize I’ve done absolutely nothing to make psychiatry fun or interesting.  In fact, dear reader, you might think I’m a pretentious pedant, obsessed with irrelevant details that have nothing to do with what my patients really need.  And you know what?  You might be correct.  Treatment of depression by family practice docs?  BORING!!  A possible biomarker for cocaine relapseWho cares????  A new insomnia medication?  A real sleeper…

I realized today that I’m doing it all WRONG.  Not only can psychiatry be fascinating, but it can be cool.  As cool as a rap video.  Because that‘s what matters nowadays, right?  Don’t believe me?  Take a look at Steve Stahl’s DLPFC Rap:

No wonder I find psychopharmacology so dry.  It’s because I don’t realize how BADASS it can be!!!  I’m sitting here in my office, questioning antidepressant mechanisms, poring over datasets and p-values, and reading up on esoteric new interventions like concreteness therapy for mood disorders.  In the meantime, Steve Stahl and his NEI Global crew are partying on the beach in San Diego, rapping about the DLPFC.  It’s true.  I’m a loser.  Lame.  A real D-bag.

The DLPFC, for those “in the know,” is the dorsolateral prefrontal cortex.  I used to know it as Brodmann area 46, a cortical area responsible for executive function, planning, organization, and working memory.  But that’s boring sh*t for old farts like me, I guess.  After watching the NEI Global clip, I now know it as “all I need to know.”  That’s pretty tight.  It’s also “where the money is,” which is even more badass.  Dollar bill, y’all.

Why are those old, gray-haired APA dinosaurs spending all their time writing the new DSM-5???  Why do the guys in the journals recommend brain scans and genetic screens and personality tests and long-ass interviews???  Yo, get it together, Steve Stahl has already figured out that the DLPFC is responsible for “executive function, attention, concentration, impulses, emotions, obsessions, compulsions, motor [?], fatigue, ruminations, worry, pain, negative symptoms, guilt, and suicidality.”  What more do you need to know, bro???

So now, when a psych resident asks me what causes obsessions or suicidality, I can just answer, “Yo, homeboy, it’s the DLPFC.”  Then I can tell him to find a drug that acts on the DLPFC and say, “prescribe that sh*t!”  Even better, when a patient comes to my office and complains of pain or guilt or concentration problems, I can just whip out one of Stahl’s epic pix and say, “Chill out, sister, homey’s got yo back” and write a script for something that works on the DLPFC.  As the video says, “most of the symptoms are in the PFC!!!!”  Bitchin’!  Another satisfied customer!

Of course, I am kinda pissed off now because my med school profs and residency mentors made me study all that stuff about brain development, cognition, behavior, PLUS all that neuroanatomy sh*t not involving the DLPFC.  WTF???!!!!  Major waste of time, LOL!!!!!  ‘Cuz the DLPFC seems to be where it’s at (where’s this Beck Depression Inventory?).  All I need to do now is grab Stahl’s book or attend an NEI Global conference—or, better yet, look for drugs that affect the DLPFC—and I’m good to go!

Hey, mental illness is no laughing matter.  But learning about the part of the brain that causes mental illness can be LMFAO, can’t it??

[Thanks to the Neurocritic blog for the link to the DLPFC rap.]

“We’re Doctors. We Prescribe Drugs. That’s What We Do.”

November 29, 2011

One of my most vivid memories of medical school was during my internal medicine rotation, when it had become apparent to me that, despite spending my pre-clinical years studying complex pathophysiology and pharmacology, and the fine art of history-taking and the physical exam, the actual clinical work seemed to be more like a numbers game.  I felt like I was always responding to a data point:  a blood pressure reading, a glucose level, a WBC count.  And the response always seemed to be the same:  I prescribed a drug.

To my immature medical mind, it seemed almost too simple.  I thought a computer could do it just as well.  When I commented to my attending physician that we seemed to be emphasizing medications over lifestyle changes, alternative therapies or preventive measures a patient might take, he responded, “We’re doctors.  We prescribe drugs.  That’s what we do.

Fast forward about 10 years.  I now work part-time in teaching hospital.  One of my responsibilities is the supervision and training of psychiatric residents and medical students.  Recently, one of the students asked whether her final exam for the psych rotation would include questions about psychotherapy, to which my colleague responded (and yes, this is a direct quote), “No.  We’re doctors.  We prescribe drugs.  That’s what we do.”

The echoes of medical school resounded loudly.  But the words from med school professor had had a very different impact on me a decade ago than those spoken by colleague just last week.  While I accepted my professor’s words as the insight of a seasoned expert about what really matters in medicine, my psychiatrist colleague’s comments rubbed me the wrong way.

It made me wonder, has medicine changed?  Or have I?

I (and numerous others) have written extensively about how psychiatric drugs don’t work nearly as well, or as frequently, as advertised.  Others have written eloquently about the inherent dangers of psychiatric medication—a viewpoint which has been, at times, exaggerated, but to which I have become more sympathetic over the years.  These are two reasons to shudder at the fact that psychiatrists-in-training are being taught to emphasize the pharmacological approach.

But more important to me is the fact that, with comments like these, we psychiatrists are actively positioning ourselves to rely on a treatment philosophy that may well have run its course at some point in the not-too-distant future.  (Will today’s psychopharmacologists face a fate like those of the psychoanalysts of the 1950s and 60s?)  If students and residents increasingly see psychiatry as a pharmacology-oriented specialty, they will be less likely to explore other interventions that may ultimately prove to be more helpful to their patients.

Psychiatry is already ceding territory to other professionals.  Psychotherapy is taught in most psychiatric training programs, but few psychiatrists are paid (or choose) to do therapy.  Understanding how to provide systems-based care, or integrate psychiatric care into a patient-centered medical home (PCMH) model, is not something psychiatrists are trained to do, despite the obvious drift of American medicine in this direction.  Even some areas that could arguably be considered areas of unique psychiatric expertise— developmental disorders, addiction treatment, child development, geriatric neuropsychology, psychosomatic medicine, integrated pain management, trauma recovery, to name a few—aren’t a major part of the psychiatric curriculum.  Why not?  There are no drugs that we can prescribe (and, similarly, no drugs approved by the FDA) to treat these conditions.

This gradual erosion of psychiatric training has two consequences.  First, it opens the playing field to other mental health professionals who can generally provide their services more cheaply than psychiatrists do.  While most of these specialists perform their jobs quite admirably (making the psychiatrist irrelevant, by the way), the prioritization of cost over quality may result in patients getting worse care over the long run, especially if rigorous standards are not upheld.  Secondly, because meds are still where the money is, more non-psychiatrists are getting into the psychopharmacology game.  Psychiatric nurse practitioners (who have prescribing privileges), physician assistants, family practice docs, Suboxone jockeys, psychologists (in some states), and many others see psychopharmacology as a way to keep their customers patients satisfied and to keep their offices full.  When, in the end, the data show that these patients fare no worse (or, sadly, no better) than those seen by psychiatrists, then the writing will really be on the wall for most of us.

Some readers, particularly those working in a private practice setting, might respond, OK, I see your point, but some psychiatrists really do provide comprehensive, thoughtful care to their patients.  To which I would say, yes, but they are truly in the minority.  My own career trajectory (as well as my personal life) has taken some unexpected turns, and these turns have taught me how psychiatry is practiced among the masses in “the real world,” not in the Ivory Towers of Cornell, Stanford, or UCLA.  For the majority of patients and providers, psychiatric treatment is a numbers game, and the numbers are easy to follow:  More patients + More appointments per day + More medications prescribed = Everyone wins.

I believe that not only can psychiatrists provide better care than the medication-laden treatments we dole out today, but we have a responsibility to do so.  Four years of medical school and four years of residency provide plenty of time to learn about human behavior, emotions, the roots of motivation, child development, family systems, learning theories, interpersonal skills, coping strategies, evolutionary psychiatry, ego psychology, personality theory, human sexuality, spirituality, existentialism, psychodynamic principles, and basically everything else that makes a person tick, in addition to the basic biology of the disorders we diagnose and treat.  To dismiss this in favor of a medication-oriented curriculum that could be obtained in a weekend seminar or in an industry-funded CME course, is an insult to our intelligence, and, potentially, the downfall of our profession.

When the prescription pad becomes a hammer, then every symptom starts to look like the proverbial nail.  Perhaps it’s time for psychiatrists to dust off some other tools before it’s too late.

Buongiorno, Intermezzo

November 25, 2011

A surefire way to bring a new drug to market is to identify a characteristic of everyday life which is annoying or a nuisance—or which, in some cases, might actually reflect an underlying disease state—test a drug which has some effect on that “feature” (even a drug already on the market), and obtain FDA approval for this “new indication.”  And if that doesn’t work, you can just try to generate word-of-mouth about how well your drug works for some off-label purpose.  Thus, we’ve seen atypical antipsychotics for “agitation” in autism, gabapentin for RLS, low-dose doxepin for insomnia, as well as the widespread off-label use of Seroquel for insomnia, modafinil for chronic fatigue, and Risperdal for disruptive behavior in kids.

Earlier this week, another new drug joined this list.  Transcept Pharmaceuticals and its partner Purdue Pharma (yes, that Purdue, of Oxycontin fame) received FDA approval for “Intermezzo,” a new low-dose version of zolpidem, the drug more popularly known as Ambien.  Specifically, Intermezzo was approved for “middle of the night [MOTN] waking followed by difficulty returning to sleep.”  MOTN is not a disease in its own right, but a symptom seen in some patients with (and many patients without!) insomnia.  Intermezzo seeks to capture this market.

Zolpidem, as you might know, is already available generically in two dose strengths, 5 and 10 mg.  It’s also available in a long-acting “Ambien CR” form (actually a slow-release formulation encased in a rapidly-acting outer layer, sort of like an almond M&M or a Tootsie Pop without the stick) in 6.25 and 12.5 mg strengths.  Intermezzo is available as a 1.75- or 3.5-mg rapidly dissolving tablet.

Would such a low dose even work?  Well, if we assume that Ambien is an effective sedating agent (which it is, in most people), then patients who wake up in the middle of the night and can’t fall back asleep might truly benefit from this small dose.  The low dose might be “just what the patient needs” to put him back to sleep but still allow him to wake up and function at work (or whatever) the next day.

But why do we need a new version of the drug, with a snappy new name and an impending multimillion dollar marketing campaign?  Can’t a patient just cut a generic 5-mg zolpidem in half and use that?  Well, Transcept says that there are some possible “advantages” of Intermezzo over this more time-consuming (and less lucrative) option.  First, Intermezzo is designed to be taken sublingually (under the tongue), so it may have a more rapid effect than the conventional Ambien tablet.  (Note:  5- and 10-mg zolpidem is already available as a sublingual tablet called Edluar, and as an oral mist called Zolpimist.)  Second, and more importantly, Intermezzo’s very low dose might theoretically lead to less daytime sedation.  Readers will recall that this was the “selling point” of Silenor (ultra-low dose doxepin) back in April.

Please note, though, that I say “theoretically.”  There are so many factors determining blood levels—and subsequent effects—of medications, that there’s really no way to tell how any one individual will respond to a given dose.  In fact, the FDA originally rejected Intermezzo (3.5 mg) in 2009, concerned that mid-night dosing may cause residual drowsiness and morning impairment.  They requested more tests, including a highway-driving study, and even though Transcept’s studies showed no impairment, the FDA still rejected the request again earlier this year, concerned that some people might still have high blood levels of drug in the morning.  Transcept “met with the FDA” in September, and (without performing additional tests) they modified their application, proposing that patients be warned against taking the medication with <4 hours of sleep remaining, and that a lower dose be made available:  specifically, 1.75 mg in women (vs. 3.5 mg in men).  This was acceptable to the FDA.

(As far as I can tell, there are no published data proving that women metabolize the medication more slowly than men, but the FDA approval documents have not yet been posted.  It might just be that this was simply a reasonable explanation that would permit Transcept to get their drug to market without further phase III testing.)

Other writers have already commented on the fact that Intermezzo is just a new version of an existing drug, a sort of “me-too” agent whose niche has been cleverly created by its manufacturer.  This indeed seems to be the case.  But I have other concerns, too.

For one, conventional wisdom says that the frequent use of rapidly acting agents is a setup for substance dependence.  The regular use of zolpidem—at any dose—may cause “down-regulation” of GABA receptors, requiring greater doses of zolpidem to have the same effect over time, a phenomenon commonly observed in clinical practice.  (So a patient might start on Intermezzo and end up taking regular-dose zolpidem at 2AM anyway??  Wouldn’t that be ironic?)

But in addition to the physiological dependence, I’d be concerned about the development of psychological dependence on a drug like this one.  Patients who use pills for short-term relief (of pain, of anxiety, of insomnia, etc) develop a need—almost a craving—for those pills.  The craving is, in many cases, purely psychological.  Over time, the drug may not even be necessary, or it may serve little to no biological effect; simply taking the pill is what provides relief.  Now, if the pill were an innocuous placebo or some other mild intervention, I wouldn’t be too worried.  But opiates, NSAIDs, benzos, and benzodiazepine-like agents (such as zolpidem) are not benign, particularly when taken long-term.  Moreover, the psychological need for a bottle of pills by the bedside doesn’t cure insomnia, it creates a new dependency.  Insomniacs will need that bottle.  Moreover, they’ll be more likely to take a pill whenever they wake up, for whatever reason—whether it’s to grab a midnight snack, take a bathroom break, or to hush a snoring partner.

Of course, for some patients with insomnia, the opposite might be true:  simply the knowledge that something is available if they wake up, might help them to sleep soundly throughout the night.  Sort of like the patient with panic disorder who never experiences a panic attack—as long as she has the stash of Ativan in her purse.  Certainly some patients may benefit in this fashion, but for most, the pill bottle may be just too tempting.

(A side note: in the published phase III sleep lab study for Intermezzo, 82 patients with insomnia were put to sleep in the lab, but then awakened by the researchers after four hours—in other words, they did not experience the “natural” overnight awakening they complained about.  The patients were then given Intermezzo or placebo and, of course, the Intermezzo patients fared better.  But to me, that’s like taking 100 patients, hitting each of them with a stick, and randomizing 50 to ibuprofen and 50 to a placebo to treat the resulting pain.  Of course it’s going to work.)

In the end, we’re left with another new drug that we may not really need.  Will it be prescribed?  Of course.  Will it be given to patients who are already taking Ambien, or using benzos, or drinking alcohol?  Yes; trust me on this one (…making the FDA’s legitimate concerns about oversedation and impairment essentially irrelevant).  Will Intermezzo be prescribed in lieu of behavioral or other psychological/lifestyle measures that might treat a patient’s insomnia?  Absolutely.

So why does it exist?  Transcept estimates a MOTN market of $1.9 to $3.4 billion per year, and they’re counting on the sales staff of Purdue Pharma to help sell Intermezzo to psychiatrists and pain docs.  (As they say in their shareholder materials, “High value pain prescribers tend to be significant insomnia prescribers” and psychiatrists rank highly, too.)  Just as people want rapid relief from pain—and take ever-increasing numbers of pills to do so—they want their sleep.  Intermezzo is just one more way to satisfy that need.  But at what cost?

Why Psychiatrists Don’t Treat Addicts

November 20, 2011

Of all the conditions that psychiatrists face (almost) daily in their practice, addictive illness is easily among the most common.  There are almost 5 million drug-related emergency room visits per year, and the number of ER visits and hospital admissions for complications of drug use is undoubtedly several times higher.  In psychiatric patients, symptomatic exacerbations are often the direct result of substance (ab)use.

Addictions are captivating, both literally and figuratively.  In fact, addiction has been described by Alan Leshner, former director of the National Institute of Drug Abuse, as the “quintessential biobehavioral disease.”  Addictions arise from disrupted brain chemistry, faulty psychological adaptations, counterproductive behavioral strategies, moral decline, irresponsible social policies, spiritual emptiness, poor role models, or some combination of the above.  For the psychiatrist who professes to treat “the whole person,” who wants to “bridge the gap between mind and brain,” etc, it would seem that addiction is the “perfect” psychiatric disease.  Or, to put it another way, if psychiatric disorders are music, then bipolar disorder, schizophrenia, and ADHD are catchy Top 40 hits, while addiction is a timeless Rachmaninoff concerto.

Unfortunately to most psychiatrists, addiction instead is treated more like background noise.

To be sure, some psychiatrists are very well versed in the treatment of addictions.  Some of the most meaningful contributions to addiction treatment in the 20th century came from psychiatry.  Carl Jung’s treatment of the intractable alcoholic “Rowland H” led to the foundation of Alcoholics Anonymous.  The popular “self-medication” theory of addiction originated in the writings of Edward Khantzian, whose focus on deficient ego strength is informed heavily by psychodynamic theory.  And today, the American Board of Psychiatry and Neurology recognizes “Addiction Psychiatry” as a distinct subspecialty, requiring rigorous training, experience in chemical dependency settings, and deep knowledge of substance abuse and its treatment.

But in most psychiatric settings today, addictions are not actively treated.  In my part-time work in a county mental health department, for instance, patients with chemical dependency (CD) problems are referred out of the psychiatric setting and into programs run by non-psychiatrists.  When we admit inpatients to our psychiatric unit whose presentation was clearly exacerbated (or caused) by ongoing substance abuse, we’ll document it, but often have little (or no) consultation with the patient or the family about the importance of CD treatment.  In my residency training at a private university hospital (which had, at the time, recently closed its CD partial hospitalization program because it reportedly made no money), we frequently blocked dual-diagnosis patients from our psychiatric services, using the argument that “the addiction had to be treated first,” before we could address mental health problems.

Why is this?  Why are we reluctant to treat the one disorder that, in most patients, involves virtually every aspect of the “biopsychosocial” model that we so proudly profess to treat in psychiatry?

Personally, I can think of a number of reasons.  First of all, the definition of “addiction” is unclear to most of us; in fact, the DSM-IV defines “abuse” and “dependence,” but not “addiction.”  Some cases of addiction are obvious to anyone (“you know it when you see it”), but for the vast majority of patients, we just don’t know how to define it, much less diagnose it.  Interestingly enough, most docs do recognize that the concepts of “abuse” and “dependence” insufficiently describe the phenomenon of “addiction,” but the whole concept is amorphous, vague, and confusing—so we don’t go much further than that.

Secondly, treatment is difficult.  Psychiatrists like to have a strategy to use, ideally based on clinical trial evidence or at least a plausible “mechanism” (physiological, psychological, or otherwise) with which we and our patients can understand the disease.  The strategy may be an evidence-based manualized therapy, a standardized treatment approach, or (especially these days) a medication.  Indeed, we do have medications like naltrexone and Suboxone, but these don’t treat the addiction, when given alone (I’ll write more about that in a future post).

Third, I believe our hubris keeps us from treating what we know we cannot.  Psychiatrists know intuitively that addictions are cunning, baffling, and powerful (even if they don’t know the true derivation of that phrase).  Addictions are frighteningly illogical, patients don’t respond to sensible entreaties to stop using (as the old saying goes, insanity is doing the same thing over and over again and expecting different results), and, to make matters worse, some people get better without our help.

Furthermore, the effects of addiction interfere with what we psychiatrists really want to do with our patients.  When a patient uses drugs or drinks, it affects the response to our medications or therapy.  We may conveniently ignore someone’s ongoing drug use, but deep down we know (or at least we should know) that that might explain the patient’s symptoms or complaints more than the condition we’re ostensibly treating.  But we don’t like that.  Over time, our countertransference leads us to despise the patients as much as we despise their disease, until it’s just easier not to see these patients in the first place.

This is a huge shame.  And a huge loss.  In my opinion, addiction is not only the quintessential biobehavioral disease, but also the quintessential human disease.  What makes addiction difficult to treat (the lack of a uniform approach, the multifactorial nature of any successful strategy, the different meaning of the disease to different people), is precisely what makes it interesting.  It’s also what will keep us from ever developing a magic bullet, a one-size-fits-all treatment for addictive disorders.  Unfortunately, with our current emphasis on biological (and quick) “fixes,” I think we’ll continue to come up empty-handed.  We just have to hope that addicts won’t continue to be shunned by those of us who should rise to this unique challenge.

The Trials and Tribulations of TC-5214

November 14, 2011

The world may need to wait a little while longer for the next generation of antidepressants.  Last week, AstraZeneca and Targacept, working together on a new drug called TC-5214, released the first data from a phase III trial.  TC-5214 failed as an add-on antidepressant in a trial of 295 European patients with treatment-refractory depression.

This news is clearly a disappointment to those of us waiting for some fresh alternatives to our existing armamentarium.  But it’s also a heavy blow to Targacept, a company whose sole focus is the development of “neural nicotinic receptor [NNR] modulators” for several different diseases.  NNRs are receptors for a neurotransmitter called acetylcholine.  While (unlike serotonin or norepinephrine) acetylcholine is not one of the chemicals commonly associated with depression, a growing body of evidence over the last several years—as well as reports dating back to the 1970s—suggests that acetylcholine/adrenergic imbalances might underlie depressive symptoms.

TC-5214 is also known as mecamylamine (actually, the S-enantiomer of this compound, for those of you keeping score at home).  Mecamylamine is an NNR antagonist.  It was used in the 1950s as a blood pressure drug, due to its ability to block sympathetic outflow (technically, it’s considered a “ganglionic blocker”).  Scientists started investigating mecamylamine as an antidepressant when they observed that many existing antidepressants actually block NNRs at therapeutic doses, and also that it was effective in several animal models of depression.

Early human studies were very promising.  In 2009, phase-II trial data of 265 patients showed an average 6-point improvement in HAM-D scores when taking mecamylamine, as well as improvements on several other secondary measures.  But the phase III study failed to replicate this finding.  In fact, the failure was so colossal (and so unexpected) that Targacept lost 60% of its market value in one day (and AstraZeneca slid 3.2%, too).

These reports prompted me to look more closely at why an NNR antagonist might work as an antidepressant.  Unfortunately, the whole NNR story is rather confusing.  For starters, consider the first “N” in NNR:  it stands for nicotine, which binds to the NNR, and (as any smoker will tell you) nicotine is a mood-enhancing chemical.  Granted, the mood-enhancing effect of nicotine might not be due solely to its action at the NNR.  However, animal studies show that other NNR agonists and partial agonists do have antidepressant effects.

Two of these NNR partial agonists with antidepressant properties are cytisine and varenicline.  Varenicline, of course, is also known as Chantix, the popular smoking-cessation drug.  Indeed, several groups have found varenicline to have a “robust and sustained” antidepressant effect when added to antidepressants alone.   At the same time, however, varenicline has received notoriety for its apparent tendency to cause suicidal thoughts in some patients.  (To be sure, all antidepressants include a “black box warning” about the potential for increased suicidal thoughts, but the effects of Chantix appear to be of a different, and more severe, character.)  How to explain this paradox is unclear.

But let’s get back to mecamylamine.  It’s an NNR antagonist.  So why would both an NNR antagonist and an NNR agonist work as antidepressants?  Actually, psychopharmacologists love these kinds of questions because it gives them a chance to hypothesize a mechanism (everything in psychiatry has a “hypothetical mechanism,” you know).  Here goes:

Exposure to a low concentration of agonist [like nicotine] initially activates the nAChR, but this is then followed by a rapid desensitization.  Nicotine’s predominant effect on many nAChR subtypes over time is that of an antagonist.  However, some nAChR subtypes are more resistant to desensitization than others, and there is some evidence that certain receptor subtypes become more sensitive to repeated agonist exposure. [PDF from 2002 here]

Huh???  I’m sure I lost the non-psychiatrists (and probably most of the psychiatrists) with that passage.  The bottom line is, we really don’t know what’s happening at the nAChR/NNR, but doggone it, let’s test a bunch of “NNR modulators” and find one that works.

Targacept, the company developing and testing TC-5214, has devoted its entire research and development enterprise to NNR modulators.  The Targacept website boasts a “robust product pipeline” including candidates for “MDD [presumably, TC-5214], ADHD, Alzheimer’s disease, and cognitive dysfunction in schizophrenia.”  All of these are areas in desperate need of better therapeutics, and the relatively unexplored NNR might yield novel treatments that are particularly efficacious.  The wide range of potential compounds (and target disorders) discussed on Targacept’s website, however, make the search look more like a fishing expedition than rational drug design.  Of course, even if ONE drug turns out to be significantly more effective than anything else available, patients (and Targacept shareholders) will benefit.  But the inevitable failures (like that of TC-5214) along the way should give us pause, and lead us to rethink the “Grand Neurotransmitter Narrative” with which we delude ourselves on a regular basis.  In other words, we may learn more about psychiatry from our failures than from our successes—even if it sets us back a few notches in the clinical arena.

Which brings me to my final comments about how we learn about drug trials.  As I’ve written before, clinical trial results (successes and failures) are transmitted far more readily via the financial press than by the medical literature.  In fact, the only reason I even know about TC-5214’s poor phase III trial was because I saw the jaw-dropping 10+ point fall in TRGT (Targacept) in pre-market trading on the CNBC stock ticker last Tuesday morning.  Searching for more info online, I found some incredibly detailed and thoughtful articles on financial websites like Seeking Alpha and

On the other hand, it may be months (or, perhaps, never) before I see the TC-5214 results published in a psychiatric journal.  And even then, I’d have to hope that my employer provides access to the journal, otherwise I’d have to shell out $35 or more for a copy of the article.

In an era when it’s easy to criticize drug companies and Wall Street for their corruption of psychiatry, we also have to remember that it’s those same companies and investors who publicize this information most efficiently—because there’s money on the line.  Nonetheless, it is a curious phenomenon when speculators and day traders know more about new medications, novel drug mechanisms, and R&D pipelines, than the doctors who will use these drugs, or the patients who ultimately stand to gain (or lose) the most.

ADDENDUM:   While writing this post, I also came across this post by Neuroskeptic, about another failed antidepressant trial.  A depressing week for antidepressants, I guess.

ADDENDUM 2:  Special thanks to reader L. Lundt, who points out that Targacept was spun off from R.J. Reynolds Tobacco Co. in 2000.  As of Targecept’s IPO in 2006, RJR owned 5.8% of the company.


November 9, 2011

As I mentioned in my last post, I am currently enjoying the bliss and happiness of wedded life.  And to answer one obvious question, no, my wife and I are not on a honeymoon.  We’re putting that off until later.  (Otherwise, I’d have a lot of explaining to do right now!!)  However, amidst the joy and pleasure of the last few days, I’ve received a few inquiries from my regular readers and Twitter followers, particularly those who know me well.  Specifically, they want me to explain who the “lucky woman” is.

In other words, they’re asking me—as they would any professional writing about his or her field of expertise—to disclose any potential conflicts of interest.  I figured it’s best to put it out in the open, once and for all:  I’m married to a pharmaceutical sales rep.

At first, I wondered whether such a disclosure was necessary.  This blog is not a commercial enterprise (i.e., I make no money from it), my posts aren’t intended to guide practice, and my writing—like that of almost anyone in the blogosphere—represents my own personal opinion.  Besides, I’ve been up front with my employers, and colleagues, and peers about my relationship, and it has never presented a problem.  Nevertheless, I know that this blog has attracted attention from other mental health professionals and from some patients and certain websites that advocate on behalf of patients, so I believe it’s only right to disclose this fact.

For readers who only know me from my blog posts, this disclosure may come as a surprise.  And more specifically for those who understand modern psychiatry or pharma sales (or both), it might very well be a reason to question what I write on this blog.

How so?  Well, I could, for instance, advocate in favor of my wife’s drug but for none of her competitors’.  I could write negative stories about other medications but nothing critical about hers.  Or, unbeknownst to readers, my wife and I could share detailed information about patients—or about the inner workings of the pharmaceutical industry—so that I can write posts that disparage her competitors and/or strengthen her sales pitch for her drug.

I can state emphatically and unequivocally that none of the above has come to pass.

What attracted me to my wife were her wit and charm, her character, her world view (the world beyond psychiatry, that is), and her own personal background—some of which is strikingly similar to my own.  Not her smooth-talking sales pitch or the fact that I might get some perks or kickbacks from the company that provides her paycheck.  (For the record, I have received no “perks” or “kickbacks” from her employer, nor has anything of the sort been offered or implied.  Moreover, I am not in her “territory,” so my prescribing patterns have no bearing on her success, or vice versa.)

As it turns out, we share even more than I had anticipated.  She is thoughtful and insightful, yet justly skeptical and always curious for evidence to support what she says or what I prescribe.  She can engage in intelligent conversation about the future of psychiatry, but she also doubts the universal efficacy of psychopharmacological intervention.  Furthermore, just as I find myself routinely questioning conventional psychiatric practice, she is also a keen observer of her own industry.  She has been quick (and correct) to denounce the unethical behaviors of some of her competitors, many of which have come to light in the last few years (thanks, in part, to my fellow bloggers).  She also recognizes the deficiencies of the medical model of psychiatric illness—and, frankly, the limitations of her own drug—and implores her customers (i.e., doctors like me) to see their patients as whole, living beings, rather than simply as consumers of her product.

I’ll admit that some predictable difficulties have emerged in our unlikely partnership.  For instance, I have a scientific background, many years of medical training, and vast exposure to patients with complicated life stories.  She, on the other hand, is employed by a corporation, has to follow strict guidelines, and only interacts with patients (and anonymously, at that) in a doctor’s waiting room or parking lot.  Each of us is astonished by the frequent discrepancy between what she is expected to discuss with doctors, and what actually happens in the psychiatrist’s office.  And don’t get me started on the issue of what we each believe is a “fair” price for a new drug.

At the same time, however, we’ve learned from each other’s experiences.  I don’t discuss the specifics of clinical cases with her, but she understands that there are multiple dimensions to any patient (far more than the DSM-IV or clinical trials would predict).  I now know far more about how drugs are marketed to doctors, and how my colleagues use (or don’t use) such information.  Whether these observations make her a better salesperson or me a better clinician, neither of us can accurately judge.  Speaking for myself, however, I think they’ve made me a more informed—and more critical—prescriber.

So in sum, I don’t see my relationship as a conflict, but rather as a source of wisdom and insight.  Or, at the very least, a way to keep grounded in the reality of medicine as both as a healing art and as a business.

But I must conclude with one additional point.  As some of my readers know, I have had my own personal history as a psychiatric patient.  I speak with some confidence when I say that I believe I’ve overcome the challenges of my past, but I also know that nothing is ever 100% certain.  Nevertheless, my hope for rehabilitation, recovery, and ultimate freedom from long-term psychiatric care, is something I bring to every patient, because it’s a part of my own experience I wish to share with others.

Unfortunately, I know too that my history—in addition to my relationship status—makes me an “easy target” for those who wish to criticize the unholy alliances and conflicts of interest that seem rampant in psychiatry.  I believe, however, that both aspects of my past strengthen my observations—and criticisms—of the state of this field today.

In the end, I know that I cannot please everyone.  Thus, I’ll concentrate on keeping (a) myself, (b) my wife & family, and (c) my patients, happy, healthy, and empowered.  I would be overjoyed if my blog continues to educate, entertain, and inspire discussion.  But I would also understand any suspicions that may emerge among my readers.

I can only hope that I’m judged by the accuracy of my words, the novelty of my ideas, and the strength of my actions—not by any perceptions, accusations, or expectations of bias.

If I fail at this, I want to know.  I want—and need—to set it right.

Tying The Knot

November 3, 2011

I may not write anything for a few days, because I’m about to get married to the most amazing woman I know.

I’ve waited a long time for this day, and I hope for many more years of the same happiness I feel right now.

It almost makes blogging sort of… well, irrelevant.  At least for a while. 🙂

Depression in Family Practice

October 31, 2011

Which medical professional is best equipped to diagnose and treat depression?  Speaking as a psychiatrist, I am (of course) inclined to respond that only those with a sophisticated understanding of psychological assessment, DSM-IV criteria, and differential diagnosis, can accurately diagnose depression in their patients.  In fact, I’ve written about how the overreliance on checklists and rapid interviewing (which may happen more frequently in primary-care than in mental health settings) may inflate rates of depression, mislead patients, and increase health care costs.

Maybe it’s time for me to reconsider that notion.  In a fascinating article published this month in the journal Family Practice, authors from the Munich Technical University reviewed 13 studies surveying 239 primary-care providers about their experience in diagnosing depression.  The paper sheds some much-needed light on this topic, on which I have (apparently) been rather misinformed.

The take-home message from this study is one that should have been obvious to me from the start:  namely, that family practice doctors, almost by definition, are perfectly positioned to recognize depressive symptoms in their patients, simply by virtue of their long-term knowledge of their patients’ history and “baseline functioning.”  As the authors write:  “A relationship that has developed over the years [helped to] reveal symptoms of depression… When clinicians were not familiar with the patient, they acknowledged that the patient was less likely to share personal information, making diagnosis more difficult.”  In other words, how a patient’s symptoms fit into the “big picture” of his or her life is far more informative than the “snapshot” offered by a single point in time.

Similarly, I was encouraged by the fact that most family practitioners (“FPs”) don’t rely on checklists or lists of symptoms—or even the DSM-IV—to make their diagnoses.  In fact, the authors write that FPs, rightly, “express doubts about the validity of the diagnostic concept of depressive disorders” and that they “consider depressive disorders to be syndromes … where etiological and contextual thinking are more relevant than symptom counts.”  They see depression “as a problem they are faced with in their everyday work rather than as an objective diagnostic category.”  Finally, FPs typically rely on a “rule-out” strategy using a “wait and see [or] watchful waiting” approach, rather than a need to ask about a list of specific symptoms.

Wow!  Here’s a challenge:  spend an hour or two reading the DSM-IV (or any of the dozens of papers on STAR*D, or any clinical trial of a new antidepressant), then read the above statements.  Which strategy most accurately captures the phenomenology, the reality, the experience, of a patient with depression?  Yeah, I thought so, too.

It seems to me that, if we are to trust these authors and their conclusions, then family practice docs really do understand their patients, and can recognize the subtle emergence of depressive symptoms over time, more so than the specialists (like me) who might be asked for an opinion long after the disease has taken hold.

But then there’s reality.

For one thing, the depiction of the FP as “being aware of their patients’ everyday lives” might have been true for the Marcus Welbys of the 60s and 70s, but (unfortunately) not for the HMO drones, the docs-in-a-box, or the clinic rotators of today, who are saddled with more bureaucratic paperwork—or, excuse me, EMR work—than anything resembling patient care.  Family practice docs (at least in the US) are more likely to be 9-to-5 employees than true advocates for the patients on their roster.

Secondly, FPs may not be diagnosing the same “depression” that my colleagues and I see in the psychiatric setting.  The article states that FPs see depression “mainly as a reaction to emotionally draining circumstances such as other illnesses, situation at work or social factors,” and that “only a minority of FPs saw depression as … a biochemical imbalance.”  People can indeed become “depressed” after breaking up with a girlfriend, losing a job, or being diagnosed with cancer.  But is this a “chemical imbalance” that we should treat with Prozac and Abilify?  Eh, maybe not.

In a similar vein, the authors admit that “primary care patients with depressive disorders tend to be less severely depressed [and] experience a milder course of illness.”  As it turns out, those are precisely the patients who tend not to respond to antidepressant therapy.  Furthermore, the authors write that these patients have “more complaints of fatigue and somatic symptoms, and are more likely to have accompanying physical complaints.”  This seems like exactly what one might expect:  patients with fatigue, exhaustion, or any somatic complaint (nausea, diarrhea, constipation, headache, sexual dysfunction, acid reflux, congestion, abdominal tenderness, morning stiffness, sciatica, you name it…) are the most likely to say that they feel generally pretty crappy.  Or, to use the authors’ words—and the psychiatric vernacular—”less severely depressed.”

So family practice docs—those on the “front lines”—may be the most qualified to diagnose depression (or any mental illness, for that matter) because of their experience and knowledge of their patients.  But this is only true if they actually KNOW their patients (which is less likely in this age of mangled managed care), and if these same doctors recognize the difference between clinical depression and environmental triggers that, for lack of a better word, just plain suck.

Given the above caveats, can (or should) depression be diagnosed and treated in the family practice setting?  Perhaps “depression” can, while “Depression” may still be within the realm of the psychiatric professional.  Until we determine the best way to distinguish between the two, let’s make sure we attend to patients’ symptoms in context:  in the context of their long-term history, environmental triggers, and life events.  These may be precisely the situations in which the family practitioner knows best.

[If any reader would like a PDF copy of the article referenced here, I’d be happy to send it to you.  Please email me.]

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