(Mis)informed Consent

December 20, 2011

Over the years, the practice of medicine has become less of an art, and more a process of crossing T’s and dotting I’s.  “Treating the chart” has become, in many ways, more important than treating the patient, and it seems that the pen—or, rather, the electronic medical record—has emerged as a more valuable tool than the stethoscope or reflex hammer.

For psychiatrists, one of the pesky little details of any office visit is obtaining “informed consent.”  Most commonly, this is the document—signed by the patient—stating that he/she has been fully informed of the reason they’re being prescribed a medication, the potential risks of taking said medication, and any possible alternatives.  Most private insurers and hospitals, and all Medicaid programs, require this documentation in the charts of patients seeing mental health specialists, and (at least in my experience) these documents are frequently sought in chart audits.

What do I mean by “pesky”?  Put briefly, the process of obtaining informed consent can be time-consuming, and some doctors worry that it might actually interfere with treatment.  In a 2004 survey, for instance, 44% of psychiatrists reported that “informed consent … increases patients’ anxiety.”  With respect to antipsychotics, nearly 20% of psychiatrists in the same study admitted “it is good practice to withhold information about tardive dyskinesia from some patients.”  As a result, patients are often poorly informed about the meds they take.  In a 2001 study of psychiatric inpatients in Scotland, fewer than half knew the reason they were receiving medication, the side effects of those medications, or even remembered getting an explanation from staff.  (But, according to the survey, far more than half were “happy to take all medications”!!)

I was recently asked for some suggestions on how to improve the medication-consent process in my outpatient clinic.  I must admit, the current process is atrocious.  Our forms are 10+ years old, with general descriptions of each class of medication (and, of course, they lack any drug introduced in the last decade); and they have that “photocopy of a photocopy” appearance, with faded margins and text at a crooked angle.  But hey, no big deal—they’re just papers to sign and stick in the chart, basically.  In the community clinic where I work part-time, the process is even more rudimentary: we have one generic form with no drug names or descriptions; the front-desk staff asks each patient to sign the form before each visit, and afterward I simply write in the name of the medication(s) I’ve prescribed.

In thinking of ways to improve the process, I’ve come to realize that it may provide an opportunity for some meaningful change in our treatment approach.

First of all, there’s no excuse for not describing the potential adverse effects of the drugs we use, but we must be cautious not to trivialize this process.  Most psychiatrists I know, for example, have a readymade “speech” about the potential for rash with Lamictal, or weight gain with Zyprexa, or sedation with Seroquel.  (See this post at Shrink Rap—and its comments—for more on this perspective.)  But if the patient hears this as just a “speech,” it’s less likely to be meaningful, just like the pre-flight safety lectures you hear on airplanes.  I advise my students and residents to pretend they’re prescribing to their spouse, parent, or child, and give all the information they would want to hear about each new drug.  (This includes how to stop the medication, too.)

Second, just as important as the potential adverse effects, I believe that patients need to hear more specific explanations of how the drug might actually provide some benefit.  All too often we give a feeble explanation like “this Prozac should make you feel better in a few weeks” or ” Valium might calm your nerves a bit” or “since you haven’t responded to your antidepressant, here’s some Abilify to help it along.”  We owe it to our patients (and to ourselves) to provide more detailed explanations.  To be sure, most patients don’t need to hear a molecular mechanism, complete with pKa values or details of CYP450 metabolism, but we ought to have this information in our heads, and we must know how we’re using this information to treat the patient in front of us.  When a patient asks how an antipsychotic might help their depression, or why an anticonvulsant might help stabilize their mood, we must give an answer.  (And if no good answer is possible, we need to rethink our treatment plan.)

Third, it is equally important to discuss treatment options with a patient.   When patients ask “is there anything else I can do or take?” the ensuing discussion might extend the appointment by a few minutes, but it always leads to a more collaborative dialogue (unless, of course, the patient is fishing for a Xanax prescription or a month’s supply of Seroquel to sell for cash).  A discussion of alternatives often gives an indication of what the patient wants, what the patient values, and how we can best promote the patient’s recovery.

Finally, the informed consent process really should be extended to non-psychiatrists who prescribe these agents.  Primary-care docs routinely prescribe antidepressants, benzodiazepines, psychostimulants, and mood stabilizers (and, of course, my personal favorite, “Seroquel for sleep”), without a discussion of risks, benefits, and alternatives, or (in most cases) a signed consent form.  Heck, even gastroenterologists prescribe Reglan, which is as likely to cause tardive dyskinesia as many of the antipsychotics we use in psychiatry, and pain specialists are fond of Cymbalta (an SNRI with some potentially nasty withdrawal effects) for “chronic pain.”  These providers should recognize the potential risks (and mechanisms) of psychotropics, just as psychiatrists do, and share them with their patients.

So even though we might look at obtaining informed consent as a “necessary evil,” we should instead look at it as a way to enhance treatment.  If nothing else, this would force us to think about what we do and why we do it.  It would enable us to honestly evaluate the true benefits and risks of what we prescribe, and maybe steer us in a different—and healthier—direction.

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What Can Cymbalta Teach Us About Pain?

April 29, 2011

You’ve probably noticed widespread TV advertisements lately for Cymbalta, Eli Lilly’s blockbuster antidepressant.  However, these ads say nothing about depression.  Sure, some of the actors may look a little depressed (the guy at right, from the Cymbalta web site, sure looks bummed), but the ads are instead promoting Cymbalta for the treatment of chronic musculoskeletal pain, an indication that Cymbalta received in August 2010, strengthening Cymbalta’s position as the “Swiss Army knife” of psychiatric meds.  (I guess that makes Seroquel the “blunt hammer” of psych meds?)

Cymbalta (duloxetine) had already been approved for diabetic neuropathy and fibromyalgia, two other pain syndromes.  It’s a “dual-action” agent, i.e., an inhibitor of the reuptake of serotonin and norepinephrine.  Other SNRIs include Effexor, Pristiq, and Savella.  Of these, only Savella has a pain [fibromyalgia] indication.

When you consider how common the complaint of “pain” is, this approval is a potential gold mine for Eli Lilly.  Moreover, the vagueness of this complaint is also something they will likely capitalize upon.  To be sure, there are distinct types of pain—e.g., neuropathic, visceral, musculoskeletal—and a proper pain workup can determine the exact nature of pain and guide the treatment accordingly.  But in reality, overworked primary clinicians (not to mention psychiatrists, for whom hearing the word “pain” is often the extent of the physical exam) often hear the “pain” complaint and prescribe something the patient says they haven’t tried yet.  Cymbalta is looking to capture part of that market.

The analgesic mechanism of Cymbalta is (as with much in psychiatry) unknown.   Some have argued it works by relieving the depression and anxiety experienced by patients in pain.  It has also been proposed that it activates “descending” pathways from the brain, helping to dampen “ascending” pain signals from the body.  It might also block NMDA receptors or sodium channels or enhance the body’s own endorphin system.  (Click on the figure above for other potential mechanisms, from a recent article by Dharmshaktu et al., 2011.)

But the more important question is:  does it work?  There does seem to be some decent evidence for Cymbalta’s effect in fibromyalgia and diabetic neuropathy in several outcome measures, and in a variety of 12-week trials summarized in a recent Cochrane review.

The evidence for musculoskeletal pain is less convincing.  In order to obtain approval, Lilly performed two studies of Cymbalta in osteoarthritis (OA) and three studies in chronic low back pain (CLBP).  All CLBP studies showed benefit in “24-hour pain severity” but only one of the OA studies showed improvement.   The effects were not tremendous, even though they were statistically significant (see example above, click to enlarge).  The FDA panel expressed concern “regarding the homogeneity of the study population and the heterogeneity of CLBP presenting to physicians in clinical practice.”  In fact, the advisory committee’s enthusiasm for the expanded indication was somewhat muted:

Even though the committee also complained of the “paucity of sound data regarding the pharmacological mechanisms of many analgesic drugs … and the paucity of sound data regarding the underlying pathophysiology,” they ultimately voted to approve Cymbalta for “as broad an indication as possible,” in order for “the well-informed prescriber [to] have the option of trying out an analgesic product approved for one painful condition in a patient with a similar painful condition.”

Incidentally, they essentially ignored the equivocal results in the OA trials, reasoning instead that it was OK to “extrapolate the finding [of efficacy in CLBP] to other similar musculoskeletal conditions.”

In other words, it sounds like the FDA really wanted to get Cymbalta in the hands of more patients and more doctors.

As much as I dislike the practice of prescribing drugs simply because they’re available and they might work, the truth of the matter is, this is surely how Cymbalta will be used.  (In reality, it explains a lot of what we do in psychiatry, unfortunately.)  But pain is a complex entity.  We have to be certain not to jump to conclusions—like we frequently do in psychiatry—when/if we see a “success story” with Cymbalta.

To the body, 60 mg of duloxetine is 60 mg of duloxetine, whether it’s being ingested for depression or for pain.  If a patient’s fibromyalgia or low back pain is miraculously “cured” by Cymbalta, there’s no a priori reason to think that it’s doing anything different in that person than what it does in a depressed patient (even though that is entirely conceivable).  The same mechanism might be involved in both.

The same can be said for some other medications with multiple indications.  For example, we can’t necessarily posit alternate mechanisms for Abilify in a bipolar patient versus Abilify in a patient with schizophrenia.  At roughly equivalent doses, its efficacy in the two conditions might be better explained by a biochemical similarity between the two conditions.  (Or maybe everything really is bipolar!  —sorry, my apologies to Hagop Akiskal.)

Or maybe the medication is not the important thing.  Maybe the patient’s perceived need for the medication matters more than the medication itself, and 60 mg of duloxetine for pain truly is different from 60 mg duloxetine for depression.  However, if our explanations rely on perceptions and not biology, we’re entering the territory of the placebo effect, in which case we’re better off skipping duloxetine (and its side effect profile and high cost), and just using an actual placebo.

Bottom line:  We tend to lock ourselves into what we think we know about the biology of the condition we’re treating, whether pain, depression, schizophrenia, ADHD, or whatever.  When we have medications with multiple indications, we often infer that the medication must work differently in each condition.  Unless the doses are radically different (e.g., doxepin for sleep vs depression), this isn’t necessarily true.  In fact, it may be more parsimonious to say that disorders are more fundamentally alike than they are different, or that our drugs are being used for their placebo effect.

We can now add chronic pain to the long list of conditions responsive to psychoactive drugs.  Perhaps it’s also time to start looking at pain disorders as variants of psychiatric disorders, or treating pain complaints as symptoms of mental disorders.  Cymbalta’s foray into this field may be the first attempt to bridge this gap.

Addendum:  I had started this article before reading the PNAS article on antidepressants and NSAIDs, which I blogged about earlier this week.  If the article’s conclusion (namely, that antidepressants lose their efficacy when given with pain relievers) is correct, this could have implications for Cymbalta’s use in chronic pain.  Since chronic pain patients will most likely be taking regular analgesic medications in addition to Cymbalta, the efficacy of Cymbalta might be diminished.  It will be interesting to see how this plays out.


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