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Obesity-Related Anxiety: A Me-Too Disease?

April 15, 2011

Psychiatry seems to have a strange fascination with labels.  (I would say it has an obsession with labels, but then it would be labeled OCD.)  We’re so concerned with what we call something that we sometimes ignore the real phenomena staring us in the face every day.

Consider social anxiety disorder (SAD).  Some have argued that this is simply a technical, high-falutin’ label for general shyness, which even “normal” people experience in varying degrees.  There are indeed cases in which someone’s shyness can be horribly incapacitating—and these cases usually benefit from specialized treatment—but there also exists a broad gradient of social anxiety that we all experience.  If I spend too much time worrying about whether the shy patient in my office meets specific criteria for SAD, I might lose sight of why he came to my office in the first place.

So a news story this week caught my eye, with the headline “Obese People Can Suffer From Social Anxiety Due to Weight Alone.”  To a non-psychiatrist, this statement probably seems self-evident: people who are overweight or obese (just like people with any other aspect of their physical appearance that makes them appear “different from normal”) might be anxious or uncomfortable in social settings, simply because of their weight.

This discomfort doesn’t meet criteria for a DSM-IV diagnosis, though.  (At this point, you might ask, but who cares?  Good question—I’ll get to that below.)  The DSM-IV specifies that the symptoms of social anxiety must be unrelated to any medical condition (of which obesity could be considered one).  So if you’re overly self-conscious in social situations due to your weight, or due to an unsightly mole on your face, or due to a psoriasis flare-up, or because you’re a dwarf, sorry, you don’t “qualify” as SAD.

Apparently some researchers want to change this.  In a study to be published this month in the journal Depression and Anxiety, researchers at Brown University and Rhode Island Hospital investigated a large number of obese individuals and found that some of them have social anxiety due to their weight and nothing else, resulting in “greater impairment in social life and greater distress about their social anxiety” than those obese patients who had been diagnosed with (non-obesity-related) SAD earlier in life.  They argue that we should expand the diagnostic criteria in the upcoming DSM-5 to include these folks.  (Indeed, the subtitle of the article in question is “Implications for a Proposed Change in DSM-5.”)

An investigation of their methods, though, reveals that their key finding may have been a foregone conclusion from the start.  Here’s what they did: They interviewed 1,800 people who were being evaluated for weight loss surgery.  (A pre-op comprehensive psychiatric evaluation is often a requirement for bariatric surgery.)  616 people had no psychiatric history whatsoever, while 135 of them had been diagnosed with SAD at some point in their lives.  But then they found 40 additional people whom they labeled as having something they called “modified SAD,” or “clinically significant social anxiety … only related to weight concerns.”  The paper demonstrates that this “modified SAD” group had psychosocial characteristics (like work/social impairment, past/current social functioning, etc) which were strikingly similar to patients with SAD.

But wait a minute… they admit they “labeled” a subset of patients with something that resembled SAD.  So in other words, they pre-selected people with SAD-like symptoms, and then did the analysis to show that, sure enough, they looked like they have SAD!  It’s sort of like taking all the green M&Ms out of a bowl and then performing a series of chemical and physical tests to prove that they are green.  OK, maybe I shouldn’t have used a food analogy, but you get my point…

I don’t mean to be weigh too heavily (no pun intended) on study’s authors (for one thing, the lead author shared a draft of the article with me prior to publication).  I know why articles like this are written; I’m aware that the medical exclusion has made it impossible for us to diagnose SAD in many people who actually have debilitating anxiety due to some obvious cause, like obesity or stuttering.  And this is relevant because we have to give a DSM code in order to be paid for the services we provide.  As with much in life, it’s often all about the money.

But if that’s the only reason we’re squabbling over whether obesity-related anxiety deserves the DSM seal of approval, then I’m sorry, but it’s another example of psychiatrists and psychologists missing the point.  Whether we call something SAD—or depression, or panic disorder, or ADHD, or bipolar disorder, or whatever—means less to the patient than what he or she actually experiences.  Admittedly, we do have to give a “diagnosis” at some point, but we need to ensure our diagnoses don’t become so homogenized that we end up looking at all of our patients through the same lens.

The 40 obese Rhode Islanders who are socially distressed due to their weight probably don’t care whether they’re labeled “SAD,” “modified SAD,” or anythingelse, they just want help.  They want to feel better, and we owe it to them to get our heads out of our DSMs and back into the therapeutic setting where they belong.

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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.


What Does a Diet Drug Have in Common With a Swiffer?

February 8, 2011

What does the new anti-obesity drug Contrave have in common with the Swiffer?

Yes, I’m talking about that Swiffer, the cleaning tool that is essentially a dry mop with disposable dusters that attach to a dispensible handle.

When the Swiffer was first introduced, it was a revolutionary product.  And it remains a top seller for Procter & Gamble, its manufacturer.  But in reality, it’s not exactly a revolutionary idea.  In fact, my mother, in fact (an expert cleaner in her own right, much to my childhood chagrin) used to remark that she could have become a millionaire if she had marketed her own idea for a “homemade Swiffer”:  wet paper towels or dryer sheets wrapped around a broom head.  The Swiffer is one of those miracles of “good design”— an idea that is elegant in its simplicity but surprisingly effective in its application, and I’m sure it has led thousands of housewives (okay, and househusbands, too) to lament, “why didn’t I think of that?”

Enter Contrave.  What exactly is Contrave?  It’s a weight loss drug being developed by Orexigen Pharmaceuticals, Inc.  It’s not available yet, but you may have read about it in the business pages a few weeks ago, when Orexigen’s stock price (symbol: OREX) took a 72% nose dive in a single day after the FDA rejected it, recommending further study of the drug to rule out cardiac toxicity.

Like the Swiffer, Contrave is nothing terribly new; it’s a re-packaged “combination drug” consisting of two commonly used medications that psychiatrists and other doctors have been prescribing for years:  bupropion and naltrexone.  Bupropion (more commonly known as Wellbutrin or Zyban) is frequently used for the treatment of depression (and has been shown to cause some weight loss on its own).  Naltrexone (ReVia or Vivitrol) is an opiate antagonist and has been used in the treatment of alcoholism, opiate dependence, and impulse-control disorders.

In a clincial trial published last year, the combination of 360 mg bupropion (a respectable dose for depression, although not a dose most doctors would start with, right out of the gate) and either 16 or 32 mg naltrexone (a slightly lower dose than we use in alcohol dependence), was associated with an average 5.0% or 6.1% weight loss, respectively, over a one-year period (vs. 1.3% in the placebo group).  A related study, whose results were submitted for FDA approval, used similar doses and found that half of the patients taking Contrave lost >5% of their body weight.

So here we have a novel agent that shows some efficacy in a notoriously hard-to-treat condition, but which is not really a novel agent at all.  Just like the Swiffer is a “gee-whiz” product that is clever, remarkably useful, but conceptually quite simple.

But this is where (in my opinion) the similarities should end.  Very few people would blame Procter & Gamble for developing a product that fills a niche but is really an overpriced combination of some readily available (and much cheaper) materials.  Frugal consumers can pass on the Swiffer and make their own, while plenty of others are willing to pay the premium for the convenience of the name-brand product.  And I think we’d all agree that people can spend their money on household cleaning supplies in whatever way they see fit.

But in medicine things are different.  When a product receives FDA approval for a given indication (especially a disease as prevalent as obesity), it’s an automatic market; plenty of doctors will prescribe it, and insurance companies & public insurers like Medicaid will cover it.  Simultaneously, you can bet that a well-orchestrated promotional campaign will rally millions of customers to “ask their doctor” about this “brand new diet drug” they saw on TV.  And Orexigen will most certainly charge a hefty premium over the component costs of bupropion and naltrexone alone, to recover the costs of clinical trials and to return a profit to its shareholders.  To be sure, as doctors learn that Contrave is actually a combo of two cheaper drugs they can easily prescribe, they might prescribe less of it, but not before a huge market is created and exploited.

Ingenuity is a wonderful thing, especially when it’s brought to bear on problems that are notoriously difficult to solve, whether it’s the obesity epidemic or that mess on your kitchen floor.  However, when a manufacturer repackages old products under a new name and charges a hefty premium for it, we need to be aware of this, and make decisions accordingly.  While most consumers don’t mind paying an extra few bucks for the convenience of a Swiffer, we should think twice about allowing our cash-strapped medical system to shell out the billions for a “blockbuster” drug like Contrave.


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