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.

Carlat on mindless psychiatrists

My fellow psychiatrist and blogger Dr. Daniel Carlat has an article in this weekend's New York Times Magazine.  "Mind Over Meds" is a memoir of Dr. Carlat's growing realization that psychiatry can't be done well in 15-20 minute medication visits, that talking to patients as people is important too. I'm generally a fan of Dr. Carlat.  His blog is one of the few listed on my blogroll (the short list of links over there on the right of this page).  He writes well, and I share his skeptical attitude toward overzealous promotion of psychiatric drugs to our profession and the public.  "Mind Over Meds" is a good article: Carlat reviews the swing from the "brainless" psychiatry of early 20th-century psychoanalysts, to the "mindless" psychiatry of today, where symptoms are treated with medications and the patient may be lost in the process.

This is all on target, and I appreciate how Dr. Carlat is willing repeatedly to make it personal and write about revisions in his own thinking — as he did in this prior NY Times Magazine article, also well worth reading.  The gist is that psychiatry has painted itself into a corner by limiting itself largely to psychopharmacology, i.e., medications, and ceding psychotherapy — understanding the patient as a person — to other mental health professionals.

Unfortunately, "Mind Over Meds" goes off the rails in two ways.  The less important is a passage that I have to believe is just badly worded, as it seems to denigrate psychologists and other non-psychiatric therapists:

Like the majority of psychiatrists in the United States, I prescribe the medications, and I refer to a professional lower in the mental-health hierarchy, like a social worker or a psychologist, to do the therapy. The unspoken implication is that therapy is menial work — tedious and poorly paid.

A couple of early commenters have already chided Dr. Carlat for this "mental health hierarchy" language.  Discussing whether mental health professionals constitute a hierarchy is beyond my scope here, but I believe Dr. Carlat is well aware that the expertise of many psychologists (for example) to do psychotherapy surpasses his own.  In fact, he has recently taken a contrarian position in favor of granting psychologists prescribing privileges.  I doubt he meant this talk of hierarchy as a putdown, but he should have been more clear.

The bigger gaffe is that the article ultimately calls for psychiatrists to do "some sort of psychotherapy... when our patients need more from us than just medication."  Dr. Carlat seems to be satisfied with a little support here, a few extra minutes of listening there.  However, that isn't psychotherapy except in the most meaningless, hand-waving sense.  That is just listening to one's patients, something every doctor should do, from dermatologists to orthopedic surgeons.  I hate to say it, but it's no wonder health plans won't pay for that.  It used to be part of the job, not something extra.

Psychiatrists have a lot more going on than mere doctor-patient rapport — or at least we used to.  Even psychiatrists who choose not to conduct psychodynamic therapy still learned, or should have learned, about psychodynamics, an intellectual and historical cornerstone of our field.  A psychiatrist's work needs to be psychodynamically informed even if he or she only prescribes medication.  As the most obvious example, a dynamic understanding may shed light on a patient's medication non-compliance and help to address it.  Even better, a dynamic understanding of the patient may obviate the need for medications at all.  (To those who argue that psychodynamics has been supplanted by cognitive-behavioral therapies, I note that Dr. Aaron Beck, the founder of cognitive therapy, was a psychoanalyst first.  Even cognitive therapy works better if it is conducted by a psychodynamically informed therapist.)

Dr. Carlat should have gone farther.  Psychiatry needs to retake the position that we strive to understand and heal the mind from the molecule on up  (a position taken by Freud, among many others).  It is true that this encompasses a dauntingly wide spectrum, from psychopharmacology to psychological treatment, and beyond that to social and cultural influences.  As physicians we are the only mental health discipline with the training to appreciate the whole span; other professions, like clinical psychology, may have more in-depth knowledge and treatment skills regarding a particular part of this spectrum.  Of course, any given psychiatrist may choose not to practice at all of these levels — probably cannot, given the sweeping range.  But it is the essence of psychiatry to know about the full spectrum, and either offer whatever treatment is needed at any level, or refer the patient to a professional who can provide it.

It is necessary but not sufficient to see a patient behind the symptoms, to listen.  It is also incumbent on psychiatrists to conduct real psychotherapy, dynamic or otherwise, when sitting with a patient for 50 minutes and charging for it.  Ceding "real" therapy to others has diminished our field and has turned most psychiatrists into technicians.  "Mind Over Meds" is the right title for a much deeper topic.

Politics, religion, and ADHD meds

Cross-posted from Technorati with permission.

At a dinner meeting a couple of weeks ago I met two psychiatrists who work at Kaiser Permanente, the large HMO system that boasts a 24% health insurance market share in California.  (This has nothing to do with my story really.  I just think it's amazing that a quarter of all insured Californians are Kaiser patients.)  As we described our practices, I mentioned that I recently helped a patient stop his Adderall, the amphetamine combination drug given for Attention Deficit Hyperactivity Disorder or ADHD.  The patient had come to me on a very high dose and was complaining of many side-effects: anxiety, muscle twitching, severe insomnia, weight loss.  I gradually tapered and eventually discontinued the stimulant over several weeks, with resolution of most of these symptoms.  He thanked me and said he felt much better.  I related this story with some pride, and mentioned to my dinner companions that I've had more success stopping high-dose medication, especially for ADHD, than I've had starting ADHD medication.  Moreover, I opined that ADHD is too readily diagnosed in adults, resulting in a lot of unnecessary amphetamine being prescribed.

I had not anticipated how odd these statements sounded coming from a psychiatrist.  One of the Kaiser docs, a child psychiatrist, quickly noted how many kids she'd helped by identifying and treating their ADHD.  It's an under-recognized problem, she assured me.  The other psychiatrist only saw adults, yet he too underscored how Adderall, Ritalin, and other stimulants helped his patients.  Someone mercifully changed the subject, and we let the matter drop.

It got me thinking though.  First, could we all be correct?  I have no reason to doubt the experience of child psychiatrists who see their young patients perform better, achieve more, and get along better with others when treated for ADHD.  I don't see children myself, and am basically a bystander in the debates over medicating children for ADHD and behavioral problems.  Moreover, even in adult psychiatry I believe that prescribed stimulants can sometimes help, not only for ADHD but also for depression in the severely medically ill, and in some other situations.

But my own experience has led me to be cautious.  "Adult ADHD" is a fad.  Its rate of diagnosis and treatment have skyrocketed in recent years, for no good scientific reason.  I get calls all the time from people who have diagnosed themselves using a simple online checklist and are seeking an MD to rubber-stamp an amphetamine prescription.  Since amphetamines are performance-enhancing even in normals and have street value as drugs of abuse, these potential patients put me in the uncomfortable position of second-guessing their request.  I'm not saying adult ADHD doesn't exist — in fact, I'm sure it does — but this isn't the kind of relationship I want with patients.  So I tell callers I don't do ADHD evaluations, leaving me with lingering regrets about thwarting the subset — I don't know how big it is — who have a legitimate need for this treatment.

And frankly, I've seen these medications over- or mis-prescribed by my fellow psychiatrists on a number of occasions.  In addition to the patient mentioned above, for nearly a decade I've seen a distinguished senior academic for medication treatment of anxiety and depression.  He's never had an ADHD diagnosis.  Nonetheless, he asked his psychiatrist back in 1993 to add Ritalin because a relative with ADHD benefited by it.  He's been on it ever since, 16 years.  I tapered the dose down by more than half, but my patient resists using less, even though it likely worsens his anxiety and he needs medication for sleep.  At this point I expect he's on it for life.  Another patient of mine, a young woman without an ADHD diagnosis but with a history of anorexia, had been prescribed 40 mg of Ritalin daily by her prior psychiatrist.  It helped her concentrate, but also suppressed her appetite, which was a major psychological issue for her.  We tapered down the Ritalin and discontinued it over about a year and a half, at which point she was doing well and reconciling with her mother — who, my patient said, had abused Ritalin herself for a long time.

Well, you get the idea.  I'm not opposed to psychostimulants, honest.  And I do believe ADHD is a serious problem and that it responds well to medication, along with other treatment.  However, I also believe that, in adults anyway, inattention and hyperactivity can mean lots of things.  I believe stimulant medications that cause anxiety, insomnia, loss of appetite, teeth grinding, high blood pressure, and other side-effects ought to be used judiciously.  (And I also believe that a patient needs to have had symptoms by age 7 to fulfill DSM-IV diagnostic criteria for ADHD.)

Some of the most contentious, polarized arguments in psychiatry revolve around ADHD and its treatment.  Are we poisoning our children with stimulants?  Or leaving thousands to suffer unnecessarily?  So far, these arguments still generate more heat than light.   The main thing I learned at the dinner meeting I attended is that, like politics and religion, ADHD and its treatment remains a touchy topic in polite conversation.

"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.