Expert Opinion in Psychiatry

I think it might be time for us to reevaluate who the "experts" in psychiatry are (and this might apply to many more fields as well). Typically, as the story goes, "experts" in any field are the academics, those who spend time doing research, reviewing research, administrating departments, and teaching medical students and residents. It is not an understatement that provision of clinical care is often not the primary focus of people in academic positions, especially when a bulk of their salaries come from research or their other additional endeavors. This is especially the case when so-called "thought leaders" or "experts" in psychiatry spend a good deal of time at conferences that can last up to a week. Many of these folks attend multiple such conferences a year. So how is it, then, that they can claim to be "expert" in a field with which they have diminishing clinical contact? And when --and this is a big and-- the quality of psychiatric research is so poor and the data on psychiatric medication (as a whole) is miserable, how is it that these "thought leaders" can claim to be expert in anything but the status and results of meager research? ...And I won't even go into the trickery that study authors use to tease-out significant results from largely failed studies.

Some academics argue for a pragmatic approach to psychiatric diagnosis and treatment; most notably these include the architects of the recent DSMs. It seems to me (and in my lowly clinician opinion) that a pragmatic approach would involve interrogating the experience of actual practicing clinicians, those at the front-lines of psychiatry. I guarantee that the average psychiatrist is seeing hundreds, if not thousands, more patients than your run-of-the-mill "expert" or "thought leader," each year.

I am arguing here for an elevation of the importance and relevance of practicing non-academic psychiatrists and their cumulative experience, and an allowance that extensive clinical experience that leads to above-average outcomes (which is a big deal in psychiatry) would allow one to be called an expert.



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Carlat's View of Psychotherapy

So I finally got a chance to listen to Daniel Carlat's Fresh Air chat regarding the ills of modern-day psychiatry. I very much enjoyed the radio show, but I do take issue with the idea that every psychiatrist should be providing psychotherapy to all of their patients (which was implied, though not explicitly stated). I take issue with this because I have deep respect for psychotherapy -- the many forms, the training and experience required to do it well, and the relative specialization necassary to do it well. Carlat seems to be saying that psychiatric patients everywhere would be better off if their psychiatrists just 'did some psychotherapy' with them. He seems to be missing the point that there are dozens of kinds of psychotherapy, each indicated for particular kinds of patients and problems. He could spend years in CBT training, for example and still not be well suited for tackling certain kinds of borderline phenomena, for example. Further, it is not clear that Carlat is serious about providing full courses of psychotherapy, suggesting that he thinks he can provide solid therapy in 30 minute sessions. I think he'd be hard-pressed to say that a 30 minute psychotherapy session, for anything but the most rudimentary supportive therapy, is standard of care. This take is an interesting reversal of the idea that psychologists should not have prescription rights. Psychiatrists mostly think that psychologist prescribing will entail a glossing-over of very serious psychiatric and medical issues that create/exacerbate and co-occur with depression. I do think that psychiatrists should practice psychotherapy when they want to and use the very specific forms they feel competent to provide. This will necessarily include a need to keep-up with the literature, just as psychiatrists must keep up with the biological psychiatry literature. I bet that Daniel Carlat is not reading the psychodynamic, CBT, etc journals regularly.

To all the psychiatrists that want to practice psychotherapy, amen! I just recommend that you choose a style and become expert in it. Don't try to be all things to all people.
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Fast treatment of depression! Or, "I'm still in a hole, but now it's a different one." Oh, the irony.

Wanted to share this with you all, in case you haven't seen it yet:

From: Archives of General Psychiatry


A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Carlos A. Zarate, Jr, MD; Jaskaran B. Singh, MD; Paul J. Carlson, MD; Nancy E. Brutsche, MSN; Rezvan Ameli, PhD; David A. Luckenbaugh, MA; Dennis S. Charney, MD; Husseini K. Manji, MD, FRCPC

Arch Gen Psychiatry. 2006;63:856-864.

Context Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders.

Objective To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression.

Design A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005.

Setting Mood Disorders Research Unit at the National Institute of Mental Health.

Patients Eighteen subjects with DSM-IV major depression (treatment resistant).

Interventions After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion.

Main Outcome Measure Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale.

Results Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week.


Conclusions Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.

Trial Registration clinicaltrials.gov Identifier: NCT00088699.


Author Affiliations: Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, Md.


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So, ketamine has all sorts of uses-- legal and illegal. It's a hallucinogenic street drug (vitamin K, special K, etc), a dissociative anesthetic, and a research tool. It's a noncompetitive NMDA antagonist and the experience is sometimes called "getting in the hole" or simply, "the K-hole," because it makes the users feel like they are far-removed from the real world and can't move in order to interact with it. Imagine looking up from the bottom of a very deep and narrow well...

The study inolved 18 TRD patients who they randomized in a double-blind crossover study (the other week was spent giving saline). The subjects, on average, were middle-aged women with about 6 (!) prior full antidepressant trials; some had ECT. So, these are sick folks. One person dropped out of the placebo arm due to a medical problem. Noone receiving ketamine had side effects that led them to drop out. The most amazing thing about the study is that everyone got better! The vast majority of patients/subjects (71%) responded. The rest remitted (!).

What I most liked about this study was that its design is very clear. The subjects were their own controls. I also liked, well, the fact that this whole study is really awesome. I mean, rapid improvement in TRD? Yes, it's possible. You have to agree that this is one of the most provocative studies to come out in a loooong time regarding well, most anything in psychiatry (Kapur's Fast Dissociation article is one of these, too).


What I didn't like was that though the authors say the study was a double-blind crossover study, they never actually state that the folks performing the outcome ratings were blinded! This could be a big problem. Furthermore, the recruitment of the patients leaves room for speculation. The two sources of patients were very different: inpatient psych units versus newspaper ads. Hmm. Folks responding to newspaper ads may be much less acute than those already on an inpatient service. I'd like to see how response/remission sorts according to where the patients came from. On the otherhand, everyone got better, so this really isn't a big deal. It may, in fact, argue for generalizability beyond what the authors allow.

Nonetheless, this is quite an article and I can't wait to see how it plays out in psychiatry circles, academic institutions, trade journals, Big Pharma, etc
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STAR*D is Bunk

There has been plenty of news over the past year about the long-awaited and much-anticipated STAR*D trial. It was designed to be a study to address real-world approaches to treating depression, in real-world settings.

The major articles are:

Trivedi MH et al. Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice. American Journal of Psychiatry. 163:28-40 2006

Rush AJ et al. Bupropion-SR, Sertraline, or Venlafaxine-XR after Failure of SSRIs for Depression. New England Journal of Medicine. 354:1231-1242 2006

Trivedi MH et al. Medication Augmentation after the Failure of SSRIs for Depression. New England Journal of Medicine. 354:1243-1252 2006

Many reviews of the articles are already readily accessible, so I won't describe the articles here.

There are many very interesting pieces of data from these studies. One of the things that I found most interesting was the epidemiological survey of people who tend to get better with citalopram (young, educated, privately-insured women who make a decent amount of money).

Some of my concerns about the articles are:

• The authors completely botch the use of the term remission. The STAR*D authors think that remission can be determined at a single point in time. They say that scoring below 7 on the HRSD-17 or below 5 on the QIDS reveals remission. This is not true. Remission can only be determined if a patient maintains that low score over time! For all we know, the "remitters" may have become depressed again the day the trial stopped. Remember, also, that remission is not cure. The definitions of "response" and "remission" were co-opted by psychiatry from oncology. If we co-opt the words, we must also maintain their actual meanings.



• Speaking of the HSRD and the QIDS, take a gander at the "switch" paper, by Rush. The authors are running their trials from two completely different outcome measures! Look at page 1235: remission is based on a HRSD-17 score of less than 7. This is a completely different outcome measure from the primary outcome measure used in the first-step trial (the citalopram -only one): QIDS-C < 5. In a set of trials, why would the authors use different primary outcome measures?



• It gets worse! In the "augmentation" trial by Trivedi, there are two different primary outcome measures! Come on, guys! Which is it? Look at pages 1244 and 1245. Page 1244 states that the primary outcome is based on the QIDS, whereas page 1245 states that the primary outcome is based on the HSRD. Did the authors base their results and conclusions on whichever scale gave them the best data?



• Remission rates were somewhere between 28% and 33%. This isn't too great. I know many of you would say "at least we have that." I wouldn't be so sure. Take a look at the augmentation data. The augmenting drugs were bupropion and buspar. Buspar?? As an antidepressant? Buspar hasn't shown efficacy as an antidepressant. In this trial, it is effectively a placebo!. Here's the big point: we do have a placebo arm! Now, compared with placebo, the bupropion-augmentation remission rate was not significantly different: 29.7%-30.1%. Not much different from the citalopram remission rate, huh? Is this all placebo effect?

I should probably stop there. There are many very interesting things about these trials, most of which have not received attention so far (teaser...look at the suicide data). I will write about those later.

What do you think?

Mental Health and Primary Care

There is a commentary in the 5/2/2006 Philadelphia Inquirer about the re-definition of normal modes of being, as disorders. Dr. Dworkin clearly states the current problem:

Doctors now view everyday unhappiness and clinical depression as lying on a continuum, with biochemistry accounting for the whole range of human moods, from pathological to normal variants. Whether a patient suffers from clinical depression or just everyday unhappiness is immaterial because neurotransmitter imbalance is thought to be the cause of both. In both conditions, antidepressants are the treatment of choice.

Statistics affirm the new attitudes. In the United States, doctors treat both major and minor depression with medication at roughly the same rate, even as the symptoms of minor depression merge into everyday unhappiness. In one study, for example, doctors medicated 77 percent of their patients with major depression, yet practically the same proportion (68 percent) of patients suffering from minor depression received the same treatment.

And he notes one surprising cause of the medicalization of different degrees of normal experience:

Perhaps the most curious thing about the new physician attitudes is the branch of medicine that has embraced them. For the last 40 years, critics of the medical approach to unhappiness have focused their attacks on psychiatry. Yet the movement to treat unhappiness with drugs originated in primary care, which remains the force behind the movement to this day. It was primary-care doctors who overprescribed Valium in the late 1960s; it is primary-care doctors who overprescribe drugs like Prozac and Zoloft today.

From 1988 to 1998, the prescription rate for psychotropic drugs tripled in the United States, with antidepressants accounting for most of the increase. Primary-care doctors wrote 75 percent of the new antidepressant prescriptions during this period. According to IMS Health, a health-care consulting firm, from 1998 to the present, the prescription rate for antidepressants doubled again - with primary-care doctors writing the majority of these prescriptions.

Primary care doctors are the gatekeepers of modern medicine. As such, there are great demands placed upon them to optimize the use of medical resources. Throughout medical school, end even into residency, I watched, appalled, as primary care doctors usually tried to move patients with psychosocial problems right out of their offices. Psyhological concerns take time to address. And in a busy primary care office, time is tremendously valuable and the demands placed upon outpatient physicians to see as many patients as possible effectively forces well-meaning physicians to skim-over these patients and leave their concerns unaddressed. Maybe it is a misuse of resources for patients with sub/non-clinical sadness to visit a primary care doctor to have their concerns addressed, but how would they know where else to go? Primary care physicians may be exacerbating patients' problems by "treating" normality and introducing people to potentially very problematic side effects.

Really, this is pitiful and tragic: imagine a patient who comes to his doctor's office complaining of "stress" or "sadness" about a current relationship, who leaves with a prescription for an SSRI. That SSRI then causes sexual dysfunction and the patient's problems multiply.

What to do? Refer. Primary care physicians maybe should not be the gatekeepers when it comes to deciding who should get mental health care. Maybe primary care doctors should refer directly to a psychologist or a psychiatrist. This proposition really is not that outlandish. Physicians are held to the practice standards of specialists, when those specialists are available. For instance, a primary care doc who wants to set a broken leg would be held to the standard of care that is provided by the local orthopedist. If the primary care doc can't provide that level of care, he should refer, or be held liable for malpractice.

If a primary care doctor cannot handle mental illness, or even rule it out effectively (which is the problem posed by the Inquirer article), at the same standards to which psychiatrists are held, then that doctor should refer that patient to a psychiatrist, not just send the patient home with a prescription for sertraline, paroxetine, or, heaven forbid, that fluoextine/olanzapine combo for bipolar depression.

CATIE Trial Redux

So, among several other things, here are some pretty problematic portions of the CATIE trial:

1. The statistical power for results involving ziprasidone is only 58%. Any comparison involving ziprasidone has just about a 60% chance of being correct.

2. The mean dose for olanzapine is the only one of any test medication that is larger than the FDA recommended maximum. Might this be the reason it came out ahead of other trial medications? All the others were within the recommended treatment dose ranges.

3. One conclusion states that there is no difference in EPS between trial medications. The authors fail to remind their readers that patients with a history of TD were never randomized into the perphenazine group.

Phase II of the trial doesn't include perphenazine because the study designers didn't expect the drug to be as efficacious as it was. This is a shame because one dose of that medicine costs pennies compared with single doses of the other medicines. They must have recognized their mistake, because the study designers have chosen to include perphenazine again in Phase III, as a third-line medicine if two antipsychotics (Phases I and II) fail.