antidepressants

Undermedicated

under-medicatedA patient I see for psychotherapy, without medications except for an occasional lorazepam (tranquilizer of the benzodiazepine class), told me his prior psychiatrist declared him grossly undermedicated in one of their early sessions, and had quickly prescribed two or three daily drugs for depression and anxiety.  He shared this story with a smile, as we've never discussed adding medication to his productive weekly sessions that focus on anxiety and interpersonal conflicts.  Indeed, the lorazepam is left over from his prior doctor.  I doubt I would have ordered it myself, although I don't particularly object that he still uses it now and then. Of course, there's a completely innocuous way to explain this difference between his prior psychiatrist and me.  My patient could have looked much worse back then, in dire need of pharmaceutical relief.  However, he didn't relate it to me that way, and I have no reason to doubt him.  There's also the possibility that I'm missing serious pathology in my patient — that I too would urge him to take medication if only I recognized what I'm now overlooking.  But... I don't think so.  I'm left to conclude that his prior psychiatrist and I evaluated essentially the same presentation rather differently.

In particular, I'm struck by the term "undermedicated" (more often spelled without the hyphen, according to my Google search).  This judgment most often comes up in speaking about populations, as in the debate over whether antidepressants are over-prescribed or under-prescribed in society at large, or whether children are diagnosed with ADHD and prescribed stimulants too often, or not often enough.  Under- and overmedication are also commonly mentioned when describing medication management of pain, a thyroid condition, mania, or chronic psychosis in an individual.  Here the terms express disagreement with a particular dosage, where the benefits of treatment and adverse side-effects or risks are deemed out of balance one way or the other.

"Undermedicated" also implies that adding medication is the preferred or only sensible treatment approach.  While this may always be true in hypothyroidism, it clearly isn't with regard to physical or emotional pain.  The term rhetorically denies non-medication alternatives.  I would also add that, to my ear, "overmedicated" and especially "undermedicated" sound dehumanizing, as though referring to a machine that is out of adjustment, or a chemical solution being titrated on a lab bench.  Since the natural state of human beings is not to be medicated at all, it sounds a bit odd to hear someone — as opposed to one's disease — assessed this way.  Perhaps I am especially sensitized to this after reading a controversial article by Moncrieff and Cohen that highlights the "altered state" induced by psychotropics and their lack of known, specific mechanisms of action.  There is often a supposition that medication dosage correlates with symptom relief.  This is not always true of subjective states, underscoring that the complexity of human experience often belies simple "over/under" judgments.

My patient's mood and anxiety vary with his interpersonal situation.  It wouldn't occur to me to turn his "thermostat" up or down in general, even if drugs reliably could do this.  Yet I know colleagues who'd argue that one, two, or even three daily medications could help him overcome his everyday challenges of dealing with people.  These approaches point to different fundamental viewpoints in psychiatry.  Does the patient have a disease, an as-yet-undiscovered chemical (or electrical, viral, inflammatory, etc) imbalance in the brain that is best remedied by a medical intervention, accurately dosed neither "over" nor "under"?  In acute mania or florid psychosis, as in hypothyroidism, it seems to me the answer may be yes, although this is unproven and time will tell.  Perhaps, too, in severe melancholic depression.  But in social anxiety?  Self-consciousness?  Feeling discouraged about one's career?  The field's perspective on these has shifted in recent decades, such that now a hidden biological cause is assumed by default, or at least held out as a rationale for treatment.  It is only by making this dubious assumption that one can speak of undermedicating such complaints, or the people who have them.

Polypharmacy — Sloppy thinking in psychiatry 2

My second post in this series on sloppy thinking in psychiatry is devoted to polypharmacy, the medical term for prescribing multiple medications at once, especially for the same problem.  Polypharmacy is at best a risk thoughtfully taken because nothing simpler and safer will do.  At worst it's a dangerous error, exposing patients to unnecessary hazards purely as a result of laziness and sloppy thinking by their doctors.  Unfortunately, the latter is all too common in psychiatry.  Let's look at why. It has been said that the less we know about an illness, the more treatments we have for it.  Instead of one definitive cure that attacks the root of the problem, various remedies ease symptoms — not the cause — often via different mechanisms.  A good example of a definitive cure is a specific antibiotic to treat a bladder infection.  We know how bacterial infections work, and we have antibiotics to attack the root of the problem.  Ancillary treatments for fever or pain are sometimes used, but they are clearly secondary, and often optional.  In contrast, the pathogenesis of psychiatric disorders is not known, thus we have no treatments to attack the roots of these problems.  For example, antidepressants affect neurotransmitters that appear implicated in depression, but the exact way these neurotransmitters relate to the syndrome of depression is unknown.  Thanks to our ignorance, we have medications that affect serotonin, and others that affect norepinephrine and/or dopamine.  In recent years atypical neuroleptics (antipsychotics) have been approved as add-ons for treating depression, a worrisome development given their risks.

Since we don't have a definitive cure for depression, many patients report partial (or minimal) improvement from any one medication.  The prescriber may then add another on the theory that it may help via a different chemical mechanism — a theory that is difficult to confirm or refute, as we don't know the mechanism in the first place.  The original medication is not stopped: If the patient improves, why disrupt a winning combination?  And if the patient doesn't improve, we wouldn't want to withhold an antidepressant from a depressed person, would we?  Sloppy thinking all around, yet sadly common.

Similar arguments can be made for the treatment of bipolar disorder and schizophrenia.  Lacking a true understanding of pathogenesis, we treat empirically.  And empiric treatment, while often compassionate and necessary and helpful, invites the shaky logic of adding more medications hoping for more empiric benefit.

Compounding and worsening this situation is psychiatry's abandonment of parsimony in diagnosis and clinical assessment over the past 30 years.  Prior to the publication of DSM-III in 1980, psychiatric evaluation was an attempt to explain a patient's seemingly unrelated complaints using a single theory (often psychoanalytic, but possibly biological or even behavioral).  The introduction of phenomenological diagnosis in DSM-III encouraged multiple diagnoses in the same patient, say Major Depression and PTSD on Axis I, and a personality disorder on Axis II.  There was no longer any attempt to tie it all together.  This has encouraged a piecemeal approach to treatment: a medication for depression, a different one for PTSD, maybe something for sleep, and something else again for agitation due to the personality disorder.  That's four different psychiatric medications already, and we've hardly even started.  Patients with personality disorders often complain of "mood swings," so let's add a mood stabilizer like lithium or Depakote.  And they're anxious, so we could add a benzodiazepine tranquilizer like Ativan, or a beta-blocker like propranolol, or an atypical neuroleptic.  Or what the hell, all three!  We're up to seven or eight medications now, and we haven't even considered a stimulant for their ADHD — because, after all, the patient is having trouble concentrating... funny how it was never diagnosed before.  And we haven't augmented the antidepressant with thyroid supplementation, nor have we added a second antidepressant...

While 10+ psychiatric medications is clearly over top, I've evaluated a number of patients who arrive on six, often an (1) antidepressant, (2) mood stabilizer, (3) tranquilizer, (4) sleep aid, (5) stimulant, and (6) another antidepressant or mood stabilizer.  Almost without exception, I've been able to cut this list in half, and in some cases down to zero, or more often, one medication.  It's less a matter of expert medication choice, and more an aversion to sloppy thinking.  According to one study, antipsychotic polypharmacy can be simplified without harm 2/3 of the time.

Psychiatric polypharmacy is often intellectually lazy.  Needless to say, there are far more drug combinations than there are studies assessing the risks and benefits of these combinations.  Polypharmacy is nearly always an educated guess, not "evidence based medicine."  It's not even good single-case research, where one would ideally change a single variable at a time.  All too often, medications are added to treat the side-effects of other medications, as with "ADHD" in the case above, a tail-chasing exercise that only gets worse over time.  With every added medication there are added side-effects, and sometimes adverse interactions that can be more harmful than the original problem.  In my experience, generic side-effects such as weight gain and cloudy thinking are more the rule than the exception in patients taking multiple psychiatric medications.  It should happen a lot less than it does.

Once again, photo courtesy of Petr Kratochvil.

Do antidepressants work?

There is an active debate underway in the popular literature about whether antidepressant medications actually do anything chemically helpful for depressed patients.  No one doubts that many patients report feeling better, and that most evidence less depression on standardized rating scales, following treatment.  But much of that improvement appears to be due to psychological factors, i.e., the placebo effect.  The debate is over how much improvement is not due to the placebo effect.  What beneficial effects can be attributed to the active ingredients in the tablet or capsule? It's disconcerting to enter this debate decades after the popularization of antidepressants.  These are among the most common prescriptions in America: In 2010, antidepressants were the second most commonly prescribed class of drugs in the U.S., according to IMS Health.  They are so widely used that Consumer Reports publishes "best buy" recommendations about which ones to try first.  Yet recent reanalyses of efficacy data have called into question whether antidepressants help more than inert pills.  In a two-part piece in the New York Review of Books, Marcia Angell MD, the former editor-in-chief of the New England Journal of Medicine, favorably reviews these skeptical findings.  (I won't summarize the arguments here, but I do very much recommend her review.)  In the other corner is Peter Kramer MD, author of Listening to Prozac and other books, who offers a spirited defense of antidepressants in his op-ed rebuttal in the New York Times.  The 300 comments that follow the online version of the op-ed also make for fascinating reading: Many are first-person accounts of the lifesaving benefit of antidepressants.

What to make of all this?  Those conversant in research methodology will pick apart the various arguments.  Do the studies have enough statistical "power"?  Does it matter that typical efficacy studies recruit subjects who differ from patients in clinical practice?  How much difference does an "active" placebo make?  Is it preferable to use subjective mood ratings, or ratings from trained observers?  How many weeks or months should subjects be assessed?  Should subjects with co-morbidities, i.e., additional diagnoses, be included or excluded?  Are there advantages to including a third study arm (a known effective intervention) to the usual two (the drug being assessed, and placebo)?

There are many such questions that need to be resolved, and professional researchers are probably in the best position to discuss them.  Meanwhile, the rest of us are left with a seeming paradox.  Thousands — millions? — of individuals claim relief from antidepressant treatment, and virtually any psychiatrist will swear that antidepressants really have helped many of his or her depressed patients.  (This is my own experience, by the way — it's nearly inconceivable to me that antidepressants are no more than placebos.  I've seen too many patients improve before my very eyes.)  Meanwhile, there are also many patients, equally depressed, who obtain little or no benefit from antidepressants, and a large number of carefully conducted studies that find little benefit in the active ingredients of these pills, once placebo effects are factored out.

While I can't prove it, my sense is that the answer lies in the heterogeneity of depression.  Some patients get dramatically better on antidepressants (in entirely believable ways, as opposed to reactive "flight into health" and the like), some only a little, and others appear not to change at all.  Widely varying responses can easily "average out" in the usual randomized controlled trials used to assess efficacy, and could account for lackluster findings in group studies.  Since I do have some research background and training myself, I'd want to see the scatterplots of individual subject ratings, to see if they cluster into responsive, partly responsive, and unresponsive groups.

Of course, it is not a new idea that some depression responds to medication and some doesn't.  When I started medical school, psychiatrists distinguished "endogenous" and "exogenous" depression — i.e., depression that originated within the patient chemically, and depression that originated from external stress or loss.  (For a concise summary of the idea, see the first paragraph of this editorial.)  Antidepressants were thought to help the former but not the latter.

Unfortunately, that wasn't true.  As it turns out, knowing whether an external event precedes a depression doesn't predict whether an antidepressant will help.  The search has gotten more sophisticated lately, and measurable genetic subtypes may one day tell us who will benefit by antidepressants and who won't.  But we're not there yet.   At this point, we cannot predict whether an individual patient will improve with antidepressant medication.

I'll end this post by noting that the placebo effect, a vexing complication in clinical research, isn't a bad thing in real life.  If a patient feels better, I don't worry too much about who or what gets the credit.  Maybe it's the citalopram or sertraline in the pill.  Maybe it's the patient's belief in the pill and in the medical science behind it.  Maybe it's the fact that I gave the patient something that our culture imbues with symbolic healing powers.  Maybe my words were healing and the prescription was a mere distraction.  Or maybe I had no effect at all, and the patient healed himself or herself.  Usually it's impossible to know.  In my view, being a psychiatrist in clinical practice requires this kind of agnosticism and humility.

Talk doesn't pay: Comments on the NY Times article

I'd like to take this opportunity to comment on the article that appeared in today's New York Times: "Talk doesn't Pay, So Psychiatry Turns to Drug Therapy."  Gardiner Harris writes about psychiatry's shift from talk therapy to drugs, and profiles psychiatrist Donald Levin of Doylestown, PA (a suburb of Philadelphia), who felt financially unable to maintain a psychotherapy practice, and therefore shifted to a high-volume, medication-only practice.  It is clear that both the doctor and the journalist consider this a sad state of affairs.  Dr. Levin is quoted as saying: "I’m good at it, but there’s not a lot to master in medications. It’s like ‘2001: A Space Odyssey,’ where you had Hal the supercomputer juxtaposed with the ape with the bone. I feel like I’m the ape with the bone now.” That comparison is apt to rile my colleagues who are serious and careful psychopharmacologists.  But Dr. Levin is right:  Most medication management in psychiatry is tediously straightforward.  Which is why it is mostly done by primary care doctors, not psychiatrists.  In the U.S. most antidepressant and antianxiety prescriptions are written by non-psychiatrists.  (And even antipsychotics lately, but this is a different and far more worrisome issue.)  It seems to me that any self-respecting psychiatrist who limits his or her practice to psychopharmacology, i.e., medication management only, should add some value over a visit to a family doctor, internist, or pediatrician.  Either the cases seen should be harder, e.g., "treatment resistant," or the doctor should offer something more nuanced and sophisticated, or more comprehensive.  If so, such a psychiatrist will not be "the ape with the bone."  Unfortunately, my experience suggests this is the exception, and that the shift to medication management has been borne of expediency and financial pressure in many cases, not an earnest scholarly focus on advanced psychiatric medication strategies.  And for this reason, the critique that our field is increasingly populated by dumbed-down medication technicians is not the throwaway line it would otherwise be.

In saying this, I invite a rebuttal.  If psychiatrists who give meds should add something over other med providers, what do psychiatrists who conduct therapy add over other therapists?  The answer is a more comprehensive viewpoint, one that takes into account medical and bodily issues, drug interactions, and similar matters.  And the option to prescribe medications when these are needed in addition.  If we cannot add this value, we should not charge more than other therapists.

Since I have a mostly-psychotherapy practice myself, I took note of several points made in the article.  Most glaring is a starkly misleading statistic.  Harris cites a 2005 government survey showing that just 11 percent of psychiatrists "provided talk therapy to all patients."  I'm not sure why that surprises anyone.  I'm a huge advocate of psychotherapy, yet I don't recommend, much less provide, it for everyone.  It's a treatment — it's expensive, it takes a lot of time, it's often uncomfortable.  I only provide psychotherapy when I predict it will help, and when my patient agrees to it.  While I believe it would be helpful for many patients I see, I nonetheless still treat a minority of patients with medication only.  In my view, one of the best things about being a psychiatrist is that we have a variety of tools.  While I find dynamic psychotherapy more intellectually interesting and humanly engaging than writing prescriptions, I'm glad I can do both.  The 11 percent statistic is meaningless.

Another potential confusion in the article are the widely disparate fees cited, with little explanation.  At one point Harris writes: "A psychiatrist can earn $150 for three 15-minute medication visits compared with $90 for a 45-minute talk therapy session."  At least here in San Francisco, this is considerably less than either service is typically worth, even accounting for payment caps by health insurers.  Not to mention that psychotherapy is traditionally 50 minutes, not 45.  But then Harris writes about "a select group of [New York] psychiatrists [who] charge $600 or more per hour to treat investment bankers," and later notes that a nearby colleague of Dr. Levin charges "$200 for most [therapy] appointments."  The truth in my experience is that no psychiatrist starves by being a psychotherapist, even though there is more competition from other disciplines and the overall income may be less.  Talk does pay, just not quite as much.  When psychiatrists complain about comparatively low psychotherapy income, it makes me wonder why they didn't become surgeons.  Seriously, from what I gather surgery is very engaging, very satisfying, and very lucrative.  It sounds much better than doing half-hearted, half-assed psychiatry just for the income boost.

As I wrote last year, dynamic psychotherapy is more than merely a treatment technique to place on a shelf alongside medications.  It is a perspective that informs our understanding of patients even when we do not offer this specific therapy as treatment.  Thinking about our patients dynamically can help us be better medication providers, better CBT (non-dynamic) therapists, better referrers to other professionals.  Psychiatrists don't have to be psychotherapists all the time, but we do need to think psychotherapeutically all the time.  The real tragedy highlighted by the NY Times article is not one man's devolution to an "ape with a bone," nor even a profession's.  It is the loss of intellectual curiosity — of knowing there is a better way, yet choosing not to pursue it.

"Antidepressants are just a crutch"

Yesterday I evaluated a new patient, a young woman who wondered whether medication might ease her depression. She was in therapy elsewhere, and although seeing me was her idea, she was apprehensive about adding an antidepressant. I did end up recommending one, at which point she asked: "Aren't antidepressants just a crutch?" I relish this question. It is asked in anxiety, hesitation, and doubt, yet carries within it its own hopeful answer.

"Why yes," I answered with a smile. "Antidepressants are exactly that, just a crutch." I pointed out that antidepressants, and all psychiatric medications, are symptomatic treatments. Despite pharmacologic hand-waving about how they supposedly work, the truth is that no one really knows. We do know that antidepressants relieve mood symptoms, in the same way we knew aspirin relieved headaches long before we knew how. Likewise, an actual crutch relieves pressure on a healing foot or ankle without our necessarily knowing the cause or exact nature of the injury.

Like a crutch, an antidepressant provides relatively quick relief without addressing the underlying problem. There is nothing wrong with that. Relief is good, that's what crutches are for — that, and helping to prevent further injury while the part is healing. The danger is in mistaking this for treatment of the underlying problem. A crutch alone can't treat a fractured leg bone or a foot infection, and an antidepressant can't repair the family dynamics or interpersonal losses (or genetic vulnerabilities) that result in depression. Fortunately, crutches are added to treatments, such as casts and antibiotics, that do remedy the underlying problem. And my patient was in psychotherapy to address the underlying problems that led to depressive symptoms. (While we cannot as yet offer definitive treatment for bad genes, that too will come eventually.)

The old concern of psychoanalysts that mere symptom relief would lead to "symptom substitution" and a more difficult analysis has not been borne out. On the contrary, combinations of psychotherapy and medication appear in studies to work better for depression than either type of treatment alone.

I assured my patient that the antidepressant I was suggesting was indeed a crutch: a temporary means to relieve her suffering while her mind is healing. It would also help minimize further psychic injury from poor sleep, social withdrawal, undue pessimism, and perhaps suicidal urges. Like a crutch, when she is feeling better she will stop using it, secure in the knowledge it is available again if it is ever needed.